Dermal Tumors - The Basics (B Smoller, K Hiatt)

Dermal Tumors: The Basics

Dermal Tumors:
The Basics
Bruce R. Smoller
Department of Pathology
University of Arkansas for Medical Sciences
Little Rock, AR, USA
and
Kim M. Hiatt
Department of Pathology
University of Arkansas for Medical Sciences
Little Rock, AR, USA
Dr. Bruce R. Smoller Dr. Kim M. Hiatt
Department of Pathology Department of Pathology
University of Arkansas for University of Arkansas for
Medical Sciences Medical Sciences
Little Rock, AR 72205 Little Rock, AR 72205
USA USA
SmollerBruceR@uams.edu HiattKimM@uams.edu
ISBN 978-3-642-19084-1 e-ISBN 978-3-642-19085-8

DOI 10.1007/978-3-642-19085-8
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Preface
In this fourth, and final, volume of the series on dermatopathology

we conclude our framework which students, at all levels of learn-
ing, can use to continue building from in the classification and
diagnoses of cutaneous diseases.
This volume is focused on lesions arising from dermal-based
processes. The format is structured, like the previous volumes, as
a bullet-point outline of the main clinical and histologic features
with an atlas of quality images to demonstrate these points. This
format provides a small-sized reference that is easily accessible to
the sign out microscope and provides a foundation that is elabo-
rated on in the already published excellent larger texts available to
the student.
Little Rock, Arkansas, USA Bruce R. Smoller

Little Rock, Arkansas, USA Kim M. Hiatt
v

Acknowledgment
These volumes could not have been made possible without the
dedication of the dermatopathology laboratory staff at the
University of Arkansas for Medical Sciences. Their commitment
to provide high quality histology allows us the opportunity to
share the numerous images in these volumes.
As always, Bruce Smoller wishes to acknowledge his wife,
Laura, and two (now adult) children, Gabriel and Jason, for their
constant enthusiastic support and love. He would also like to
acknowledge the entire Department of Pathology at the University
of Arkansas for Medical Sciences for the honor of having worked
with them over the entire duration of this project. And, Dr. Hiatt
would like to thank her husband, Jim, and her children Stephanie,
Nicholas, Kaitlyn and Natalie for their support.
vii

Contents
1 An Overview of Cutaneous Lymphomas . . . . . . . . . 1

2 Vascular Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3 Histiocytic Proliferations. . . . . . . . . . . . . . . . . . . . . . 59
4 “Fibrohistiocytic” Proliferations. . . . . . . . . . . . . . . . 73
5 Tumors of Fat, Nerve, and Smooth Muscle . . . . . . . 103
6 Cutaneous Metastases. . . . . . . . . . . . . . . . . . . . . . . . . 123
Further Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
ix
Chapter 1
An Overview of Cutaneous
Lymphomas
• Classifications of cutaneous lymphomas

–– Two recent systems both had problems
°° Revised European-American Classification of Lym

phomas (REAL)
°° European Organization for Research and Treatment of
Cancer (EORTC)
–– REAL classification
°° Uses classification of systemic lymphomas and applies
them to cutaneous lymphomas
°° Classification based upon pathologic, genetic, and clini-
cal features and adds immunohistochemical criteria
°° Cutaneous involvement accounted for in clinical features
–– EORTC classification
°° Recognized cutaneous lymphomas as a distinct entity
°° Organ-based classification system
°° Only system that has been clinically validated for this
group of diseases; classified as indolent, intermediate or,
aggressive
–– WHO-EORTC classification
°° Consensus conference in 2005 incorporated features of
both systems to acknowledge particulars of cutaneous
lymphomas
B.R. Smoller, K.M. Hiatt, Dermal Tumors: The Basics, 1
DOI: 10.1007/978-3-642-19085-8_1,
2 1 An Overview of Cutaneous Lymphomas
–– WHO 2008 classification

°° Integrated the WHO-EORTC classification of cutaneous
lymphomas in the general classification
°° Only minor changes in terminology, except blastic
plasmacytoid dendritic cell neoplasm, previously CD4+/
CD56+ hematodermic neoplasm, previously blastic NK
cell lymphoma
• Overview
–– 3% per year increase in incidence of cutaneous lymphomas
every year since 1970
–– Cutaneous lymphomas represent a very heterogeneous
group of diseases with very different clinical presentations,
courses, treatment programs, and prognoses
–– Second most common (after GI tract) site of extra-nodal
non-Hodgkin’s lymphomas
–– Large groupings include T cell lymphomas, B cell lympho-
mas, and Hodgkin’s lymphoma
–– Overall incidence estimate of 1:100,000
–– 75% of cutaneous lymphomas are T cell lymphomas,
25% B cell lymphomas
–– Hodgkin’s lymphoma is exceedingly rare in skin
–– 5–10% of T cell lymphomas are not mycosis fungoides
• T cell lymphomas (Table 1.1)
• Mycosis fungoides (MF)/Sezary syndrome
–– Epidemiologic features
°° 0.42 cases/100,000 population

°° Overall, more than 50% of all cutaneous lymphomas
°° Incidence rapidly increased in 1970s–1980s, but now
stabilized
Table 1.1 T cell lymphomas
Mycosis fungoides/Sezary syndrome

Primary cutaneous CD30+ lymphoproliferative disorders
Subcutaneous panniculitis-like T cell lymphoma
Extranodal NK/T cell lymphoma, nasal type
Blastic plasmacytoid dendritic cell neoplasm
(Peripheral T cell lymphoma)
1 An Overview of Cutaneous Lymphomas 3
°° Twice as common in African Americans as in Caucasian

Americans
°° Twice as common in men as in women
°° Associated with 3.3X relative risk for second, non-
cutaneous malignancy
–– Clinical features
°° Usual onset in middle age (mean 55–60), but can appear
at any age
°° Starts most commonly as erythematous, slightly scaly
patches on flank and buttocks
°° Progress to plaques and ultimately tumors (in a minority
of patients)
°° Poikilodermatous variant – uncommon
°° Involvement of lymph nodes, spleen, liver only late in
course
–– Histologic features (Figs. 1.1–1.4)
°° Epidermotropic proliferation of hyerconvoluted, hyper-

chromatic lymphocytes in clusters (Pautrier’s microab-
scesses) and as single cells within epidermis
Fig. 1.1 Early lesions of mycosis fungoides show an epidermotropic lympho-

cytic infiltrate. Single atypical lymphocytes are seen lining up along the
basilar epidermis
Fig. 1.2 In more evolved lesions of mycosis fungoides, small clusters of

atypical lymphocytes and increased single lymphocytes are present in the
epidermis which also shows only minimal spongiosis and no dyskeratosis
Fig. 1.3 This case of mycosis fungoides shows only a mild dermal infiltrate
but numerous Pautrier’s microabscesses
Fig. 1.4 Variable number of eosinophils and some plasma cells are often
present in the dermal infiltrate of mycosis fungoides
°° Difficult diagnosis to make in early lesions

°° Later lesions with less epidermotropism and more cyto-
logic atypia
°° Variable number of eosinophils and some plasma cells
–– Immunologic features (Figs. 1.5 and 1.6)
°° Mycosis fungoides is defined as a neoplastic prolifera-

tion of CD3+, CD4+ T helper lymphocytes
°° CD8+ tumors are rare but are now classified as MF
°° Loss of CD2, CD3, and CD5 often seen
°° Clonal rearrangements of T cell receptor is ultimately
detected in most cases, but only 50% of early lesions.
–– Molecular features
°° T-cell gene rearrangements seen in 50–80% of patch-

stage lesions, nearly 100% of tumor stage and Sezary
cases
°° When same clone is present in two separate locations,
worse prognosis is reported
Fig. 1.5 The epidermotropic lymphocytes in mycosis fungoides most

commonly express CD4
Fig. 1.6 Loss of normal T-cell markers such as CD5 is common as in this case
of mycosis fungoides
–– Treatment protocols
°° Topical steroids
°° Topical nitrogen mustard
°° Electron beam irradiation
°° Interferon
°° Chemotherapy
°° Photopheresis
–– MF – Prognosis
°° Excellent, overall
°° Patients presenting with stage I disease have the exact
same 30-year survival as age and sex-matched controls
without MF (97–98% 10-year survival)
°° Generalized (>10% of skin surface) disease – 83%
10 year survival
°° Tumor stage disease 42% 10-year survival
°° Nodal involvement usually with less than 1-year survival
–– MF variants (Figs. 1.7 and 1.8)
°° Folliculotropic – characteristic morphology; 70–80%

5-year survival – less responsive to therapies
–– Myxoid degeneration may be seen
–– Folliculotropic MF replaces MF-associated follicular
mucinosis
°° Pagetoid reticulosis – localized patches, very epidermo-

tropic; excellent prognosis
°° Granulomatous slack skin/granulomatous mycosis
fungoides – rare; responds to radiation, but with rapid
recurrences
°° Sézary syndrome
–– Triad: erythroderma, generalized lymphadenopathy
and neoplastic T cells in skin, lymph nodes, and
peripheral blood:
(>1,000 cells/mm , CD4/CD8 ratio >10, loss of CD2,

3
CD3, CD4, and/or CD4)

Clonality of cells in blood
Fig. 1.7 Folliculotropic mycosis (A) shows an atypical CD4+ (B) lympho-
cytic infiltrate with a predilection of the follicular epithelium. Myxoid degen-
eration may be seen
–– Mean survival 2–4 years

–– Treat with photopheresis
• Primary cutaneous CD30+ lymphoproliferative disorders
–– Primary cutaneous anaplastic large cell lymphoma
–– Lymphomatoid papulosis
• Anaplastic large cell lymphoma (ALCL)
°° Primary cutaneous ALCL occurs primarily in adults

(non-cutaneous in children)
°° Most patients with solitary or localized skin lesions at
time of presentation
°° One to several nodules or small tumors

°° Ulceration may be present
Fig. 1.8 Granulomatous mycosis fungoides shows sarcoidal granulomas in

the dermis and typically lacks an epidermotrophic lymphocytic component
°° <10% with lesions extending beyond one area of skin

°° Spontaneous regression of lesions may occur
°° Minority of patients develop nodal disease but recur-
rences of skin disease are common
–– Histologic features (Figs. 1.9 and 1.10)
°° Dense dermal infiltrate of large lymphocytes with

round nuclei, one or multiple nucleoli and marked
pleomorphism
°° Minimal epidermotropism
°° Abundant necrosis
°° Often an abundant reactive, inflammatory infiltrate with
eosinophils and neutrophils
–– Immunologic and molecular features (Fig. 1.11)
°° Defined as >75% of cells expressing CD30 in skin

biopsy
°° Lymphoma cells also express CD3 and CD4 in most
cases
Fig. 1.9 Anaplastic large cell lymphoma shows a dense dermal infiltrate of

large lymphocytes
Fig. 1.10 The nuclei in anaplastic large cell lymphoma are round with one or
multiple nucleoli and marked pleomorphism. Scattered reactive lymphocytes
are also present
°° CD2, CD3, and CD5 may be absent

°° CD15 negative (unlike Hodgkin’s disease)
°° B cell variants of CD30+ lymphoma have been
described
°° t(2;5) translocation common in children but not seen in
adults with ALCL
°° Clonal rearrangements seen in most cases
°° Radiation is preferred mode of therapy for limited
cutaneous disease
°° Chemotherapy reserved for patients with generalized
cutaneous disease or systemic involvement
–– Prognosis
°° Excellent for patients with primary cutaneous ALCL
°° 10-year survival >90%
°° Much worse prognosis for patients with nodal disease
Fig. 1.11 The large cells in anaplastic large cell lymphoma express CD3
(A) and CD30 (B)
• Lymphomatoid papulosis
°° Chronic, recurrent, self-healing papulonecrotic process
°° Mostly in adults (median age 45)
°° Lesions at different stages simultaneously
°° Process may last from weeks up to 40 years

°° 20% of patients with LyP have associated lymphoma
(MF, Hodgkin’s or ALCL)
–– Histologic, immunologic, molecular features (Figs.
1.12–1.14)
°° Large, atypical CD30+ cells interspersed with a brisk

reactive inflammatory infiltrate (type B variant looks like
MF and cells do not express CD30)
Fig. 1.12 Lymphomatoid papulosis shows a dense dermal infiltrate (A) with

scattered atypical large cells (B)
Fig. 1.13 This case of lymphomatoid papulosis shows an exuberant dermal

infiltrate attenuating the overlying epidermis (A) and showing numerous large
atypical cells (B)
Fig. 1.14 The extent of large CD30+ cells in the dermal infiltrate of lympho-
matoid papulosis varies from scattered (A) to numerous (B). Diagnosis hinges
on clinical presentation
°° CD3+, CD4+, CD8−

°° T cell clonality seen in 60–70% of cases
–– Prognosis excellent
• Subcutaneous panniculitis-like T cell lymphoma (SPTCL)
°° Previously known as histiocytic cytophagic panniculitis

(at least some cases)
°° Occurs primarily in adults (median age 37–56 years), but
reported in children
°° Rare neoplasm
°° Multiple red to violaceous cutaneous nodules

°° No overlying epidermal changes except tendency to
ulcerate
°° Not painful
°° Legs and arms most common sites, followed by the trunk
°° Systemic symptoms present at time of presentation in most
patients, but nodal involvement usually only late in course
°° Dense, diffuse infiltrate of small to medium-sized lym-

phocytes in deep dermis and subcutaneous fat
°° Fat necrosis with extensive lobular involvement
°° Rimming of adipocytes by neoplastic T cells helpful, but
not specific
°° Hemophagocytosis usually prominent, as are necrosis
and karyorrhexis
–– Immunologic and molecular features
°° All cases represent T cell lymphomas

°° a/b+, CD3+, CD4−, CD8+, CD30−
°° Clonal T cell gene rearrangement
°° EBV not seen in these cases
°° CD56+, l/d+ lymphomas are similar, but much more
aggressive clinical course (different classification now in
new system)
Fig. 1.15 Subcutaneous panniculitis-like T-cell lymphoma shows a dense,

diffuse infiltrate of small to medium-sized lymphocytes in deep dermis and
subcutaneous fat
Fig. 1.16 Rimming of adipocytes by neoplastic T-cells is seen in subcutane-

ous panniculitis-like T-cell lymphoma. Karyorrhexis, shown here, is also
common
°° Systemic chemotherapy
°° Corticosteroids (systemic) – often control disease for
long periods of time
°° Radiation therapy
–– Prognosis
°° Generally favorable – 5 year survival of 80% with fre-

quent recurrences but rare systemic involvement
• Extranodal NK/T cell lymphoma, nasal type
°° In this case, primary vs. secondary not important for

prognosis or treatment
°° Skin second only to nasal cavity in terms of frequency of
involvement
°° Neoplastic proliferations of NK cells or less commonly,
cytotoxic T cells have been implicated
°° Most common in Asia, Central and South America
°° Male predominance
°° CD56+ lymphomas have a predilection for nasopharyngeal
region (used to be called “lethal midline granuloma”)
°° Multiple skin lesions may be present on trunk and
extremities – subcutaneous nodules with ulceration
commonly
°° Systemic features including fever, weight loss, lymph-
adenopathy, splenomegaly and anemia may be present
°° Hematophagocytic syndrome also common
°° Superficial and deep dermal infiltrates of atypical

lymphocytes
°° Epidermotropism is present but not extensive
°° Angiocentric and angiodestructive infiltrates are the
characteristic finding with secondary necrosis
°° Panniculitis-like infiltrate also present in most cases
Fig. 1.17 Extranodal NK/T-cell lymphoma has a superficial and deep dermal

infiltrate of atypical lymphocytes
°° Neoplastic cells often accompanied by heavy mixed

inflammatory infiltrate
–– Immunologic features
°° Neoplastic cells express CD2, CD56, and cytotoxic pro-
teins such as TIA-1, granzyme B, and perforin and are
CD3 negative
°° Almost all are EBV+
°° CD56 negative-type very rare, with much less association
with EBV infection
Fig. 1.18 Angiocentric infiltrate with complete necrosis of the vessel is seen

in this extranodal NK/T-cell lymphoma
°° Gene rearrangements usually not seen

°° Aggressive chemotherapy (cytoxan, vincristine, adriamy-

cin, and prednisone in one series)
°° Radiation
–– Prognosis
°° CD56+ lymphomas have less than 12 month median

survival
°° If presenting with only skin lesions, survival is 27 months,
compared with 5 months if they also have extracutaneous
disease
°° Most patients develop systemic disease and bone marrow
involvement
• Hematodermic neoplasm (NK blastic lymphoma) (Fig. 1.19)
–– Newly described
–– Similar cells morphologically to NK/T cell lymphoma,

nasal type
–– Express CD4, CD43, CD56, and CD123, but not CD3 or
CD20
–– EBV always absent
–– Not angiocentric or angiodestructive
–– May be derived from plasmacytoid dendritic cells
• B cell lymphomas (Table 1.2)
• Primary cutaneous marginal zone lymphoma (MZL)
°° Slightly more common in men (1.5:1)
°° Mean age 50 years – >50% are in fifth and sixth
decades
°° May represent 15–20% of all cutaneous lymphomas
°° Cases previously called immunocytoma included in this
category
°° Part of MALT lymphomas – mucosa associated lym-
phoid tissue
°° Single or clusters of red-brown papules or nodules that
usually do not ulcerate
°° Upper extremities, back and lower extremities are most
common sites
°° Face involvement uncommon
°° More than one region involved in 25% of cases
°° Systemic symptoms are very uncommon but cutaneous
recurrences common
°° Nodular dermal infiltrates involving dermis and subcutis

°° No epidermotropism
°° Reactive germinal centers with mantle zones present
°° Lymphoplasmacytoid cells present in all cases but may
represent the minority population
°° Often with monotypic plasma cells at periphery of
lesions
Fig. 1.19 CD4+/CD56+ hematodermic neoplasms show a diffuse, non-

epidermotropic dermal infiltrate (A) atypical and mitotically active cells (B)
that co-express CD4 (C) and CD56 (D)
Fig. 1.19 (continued)
Table 1.2 B cell lymphomas
Marginal zone lymphoma (MALToma)

Primary follicular center cell lymphoma
Primary cutaneous large B-cell lymphoma of the leg
Intravascular B cell lymphoma
Fig. 1.20 Marginal zone lymphoma shows a nodular dermal infiltrate, with-

out epidermotropism
–– Immunologic features (Fig. 1.22)

°° Neoplastic cells express CD20, CD79a, and bcl-2
°° CD5, CD10, bcl-6, and CD43 negative
°° Monoclonal immunoglobulin distribution in 75% of cases;
these plasma cells also express CD138 and CD 79a
°° Many CD3+ T cells present in infiltrate
°° Trisomy 3 is seen in 70% of cases
°° Trisomy 18 and rearrangement of chromosome 1 also
seen
Fig. 1.21 Reactive germinal centers with mantle zones may be present in
marginal zone lymphoma
°° t(14;18)(q32;q21) involving IgH gene on chromosome

14 and the MLT gene on chromosome 18
°° Local excision and radiation are therapies of choice for

primary lesions and local recurrences
°° European studies emphasize antibiotic therapy and
stress relationship with Borrelia burgdorferi infection
(not seen in USA) – in these cases, antibiotics should be
tried first
°° Chemotherapy only for recurrent and widespread
disease
–– Prognosis
°° Recurrences common
°° 100% survival in one study with 5-year follow-up
(median 24 months)
Fig. 1.22 Neoplastic cells in marginal zone lymphoma express CD79a

(A) and bcl2 (B)
• Primary cutaneous follicular center cell lymphoma (FCCL)

°° Occurs in middle-aged to elderly patients (mean age

58.5)
°° 1.6:1 male predominance
Fig. 1.23 This case of follicle center lymphoma shows a dense nodular
dermal infiltrate
°° When on back, previously known as “reticulohistiocy-

toma of the dorsum” or “Crosti lymphoma”
°° Usually presents as one (or several) grouped, erythema-

tous to violaceous papules or nodules without surface
changes in a localized distribution
°° Head and neck are most common locations, then trunk
°° Will gradually increase in size over years without dis-
seminating if left untreated
°° Dense, deep dermal infiltrate of lymphocytes with no

epidermal involvement and a frequent grenz zone
°° May be nodular (more common on scalp) or diffuse
°° Neoplastic follicles of lymphocytes may be difficult to
find
°° Eosinophils and plasma cells are not present
°° Mixed cell type of FCC lymphoma most common in
skin, then large cleaved type; small cleaved is least
common
Fig. 1.24 This case of follicle center cell lymphoma is composed predomi-

nantly of small centrocyte-like cells with cleaved nuclei and inconspicuous
nucleoli
Fig. 1.25 This case of follicle center lymphoma shows a mixture of small and
large centrocyte-like cells with scattered centroblast-like cells that show large
nuclei and prominent nucleoli (arrows)
°° Predominance of CD20+ or CD79a + cells in infiltrate

with scattered reactive CD3/CD43+ lymphocytes
°° Either kappa or lambda restriction in many cases
°° Bcl-2 expression uncommon in primary cutaneous FCC
lymphomas (common in nodal based lymphomas)
°° Bcl-6 expression helpful in confirming follicular nature
of cells
°° CD10 expression seen only in follicular pattern, not in
diffuse growth pattern lymphomas
°° CD5 and CD43 are negative
°° Clonality can be established in most cases, but t(14;18) is
not seen in primary cutaneous FCC lymphoma
°° Orthovolt radiation therapy to local lesions

°° Surgical excision has been used (less desirable)
°° Radiation also effective for recurrent lesions
°° Chemotherapy indicated only when noncontiguous
regions are affected
–– Prognosis
°° Local relapses present in 25% of cases (disease-free

interval was 27 months (mean))
°° Systemic spread of disease in <5% of cases
°° 5-year survival >95% independent of growth pattern
(nodular vs. diffuse), multi-focality vs. localized, or per-
centage of blasts
°° Strong bcl-2 expression and a diffuse large-cell growth
pattern may be associated with less favorable prognosis
• Primary cutaneous large B-cell lymphoma of the leg
°° Only in elder patients (median age 76)

°° 85% greater than 70 years of age
°° 3:1 female predominance in one study
Fig. 1.26 Primary cutaneous diffuse B-cell lymphoma of the leg has a
non-epidermotropic infiltrate filling the dermis
°° Large blue-red tumor nodules appearing on lower legs,
mostly multiple
°° Almost always confined to lower leg at time of presenta-
tion, but associated with rapid dissemination
°° Has been associated with lymphedematous leg
°° Dermis filled diffusely with large cells including centro-
cytes and immunoblasts
°° High mitotic rate, abundant necrosis
°° No epidermotropism
Fig. 1.27 The dermal infiltrate in primary cutaneous diffuse B-cell lymphoma

is composed of large cells with centrocyte and centroblast morphology
–– Immunologic features (Fig. 1.28)

°° Cells express CD20 and CD79a (pan B-cell markers) and
strongly express bcl-2 (unlike most FCC lymphomas in
the skin)
°° Bcl-2 expression cited as evidence in favor of classifying
as a separate B cell lymphoma (not follicular center
cell-related)
°° Usually bcl-6 positive and CD10 negative
°° Usually starts with local radiation as first choice therapy

for patients with single, small lesion
°° Systemic chemotherapy for relapses, more extensive
disease
–– Prognosis
°° 50% relapse rate

°° Median survival is 28 months (range 8–97 months)
°° 2-year survival 77%, 5 year survival 55%
Fig. 1.28 The neoplastic cells in primary cutaneous B-cell lymphoma of the

leg co-express CD79a (A) and bcl2 (B)
°° Patients with multiple lesions at time of presentation with

significantly worse prognosis than those with a single
lesion
°° Considered an intermediate prognosis lymphoma in
EORTC classification
• Intravascular B cell lymphoma (malignant angioendothe

liomatosis)
°° Also known as angiotropic lymphoma (not angiocentric)

°° Usually in adults ages 50–70 but can occur at any age
°° No gender predilection
°° Most commonly involves skin, lungs, and central nervous

system at time of presentation
°° Skin findings may appear as telangiectasias, panniculitis,
or erythematous nodules, most commonly on trunk and
lower extremities
°° Constitutional symptoms including fever and myalgias
are common
°° Hematopoietic tissues are rarely involved
°° Mild anemia
°° Ectatic vessels in dermis and subcutis occluded by non-

cohesive proliferation of large, cytologically atypical
lymphocytes
°° Lymphocytes are hyperchromatic with prominent nucle-
oli and abundant mitoses
°° Fibrin thrombi may be present
°° Small- and medium-sized vessels are involved
°° Most cases express CD20 and CD79a (rare cases are

CD3+ T cell lymphomas)
°° Aggressive chemotherapy and radiation therapy

°° Lymphoma responds poorly to both regimens
°° Some evidence that better results occur with aggressive
polychemotherapy early in course
Fig. 1.29 Intravascular B-cell lymphoma shows dermal vessels distended

with large atypical B-cells
Fig. 1.30 The cells filling the dermal vessels in intravascular B-cell lym-
phoma have irregular nuclei, prominent nucleoli, mitoses, and apoptosis
–– Prognosis
°° Very poor
°° 13-month median survival after diagnosis
°° Patients with only skin lesions have a 56% 3-year
survival
°° Patients with other organ involvement have a 22% 3-year
survival

Chapter 2
Vascular Tumors
• Vascular tumors (Table 2.1)

• Telangiectasias (Table 2.2)
• Port wine stain
–– Clinical
°° Presents at birth or shortly thereafter
°° Progressively darkens, thickens, and becomes more
nodular with age
°° Associated with Sturge–Weber syndrome, Klippel–
Trenaunay syndrome, and Cobb syndrome
°° Progressive ectasia believed to be caused by abnormal
autonomic regulation – decreased nerves present in
lesional skin
–– Histologic (Figs. 2.1 and 2.2)
°° Ectatic, thin-walled vessels in superficial to mid-dermis
°° Vascular ectasia becomes more prominent with increas-
ing age
°° Difficult to diagnose in young children (without clinical
history) – appears virtually normal
• Hereditary hemorrhagic telangiectasia
–– Clinical
°° Autosomal dominant inheritance
°° Nosebleeds in children
°° Telangiectasias appear on mucosal surfaces and diffusely
on skin
DOI: 10.1007/978-3-642-19085-8_2,
38 2 Vascular Tumors
Table 2.1 Vascular tumors
Telangiectias
Intravascular papillary endothelial hyperplasia
Hemangiomas
Lymphangiomas
Non-hemangiomatous tumors
Table 2.2 Telangiectasias
Nevus flammeus (port wine stains)

Hereditary hemorrhagic telangiectasia
Angiokeratoma
Venous lake
Fig. 2.1 Port wine stain demonstrates vascular ectasia but no increase in
numbers of dermal blood vessels. Original magnification 40×
–– Histologic
°° Ectatic post-capillary venules

°° Thin-walled vessels
°° No inflammation
2 Vascular Tumors 39
Fig. 2.2 Widely ecstatic vessels are present in the papillary and superficial
reticular dermis in port wine stains. Original magnification 100×
• Angiokeratoma
–– Clinical
°° Acquired telangiectasia
°° Epidermal hyperplasia is secondary
°° Mibelli type – multiple telangiectasias on dorsa and sides
of fingers
°° Fordyce type – multiple telangiectasias on scrotum
°° Associated with Fabry’s disease – multiple angiokerato-
mas, renal disease
°° Angiokeratoma circumscriptum is probably a true heman-
gioma (not a telangiectasia) – is probably misnamed
°° Dermal papillae expanded by dermal capillaries

°° Epidermal acanthosis with elongated rete ridges engulf-
ing ectatic vessels
°° Deeper vessels may rarely be involved
Fig. 2.3 Ectatic vessels are located high in the papillary dermis and surrounded
by acanthotic epidermis in angiokeratoma. Original magnification 40×
Fig. 2.4 The superficial, ecstatic vessels in angiokeratoma are usually con-

gested and often thrombosed. Original magnification 100×
• Venous lake
–– Clinical
°° Slowly enlarging ectatic vascular lesion usually in elderly
men with marked sun exposure
–– Histologic (Fig. 2.5)
°° Dilated vessel, usually filled with erythrocytes and often
thrombosed surrounded by marked solar elastosis
• Intravascular Papillary Endothelial Hyperplasia (IVPEH)
–– Clinical
°° Also known as Masson’s lesion
°° Tender-painful red-blue dermal nodule, often sudden
appearance and growth
°° Proliferation of endothelial cells confined to lumen of
larger, thrombosed vessel
°° Papillary infoldings may resemble angiosarcoma, but no
mitoses or cellular atypia
°° Represents a recanalized, thrombosed blood vessel
Fig. 2.5 A venous lake consists of a single ecstatic vessels in the superficial
dermis, often surrounded by marked solar elastosis. Original magnification 40×
Fig. 2.6 Intravascular papillary endothelial hyperplasia is a proliferation

of endothelial cells confined to within the lumen of a vessel. Original
magnification 40×
Fig. 2.7 Higher magnification demonstrates a florid proliferation of endothe-

lial cells forming interanastamosing channels and extravasated erythrocytes in
intravascular papillary endothelial hyperplasia. Original magnification 200×
• Hemangiomas (Table 2.3)
• Acquired capillary hemangioma
–– Clinical
°° Small, red lesions acquired in adolescence and later in life

°° Associated with increased estrogens, liver disease
°° Proliferation of dilated capillaries in the superficial dermis

Table 2.3 Hemangiomas
Acquired capillary hemangioma

Infantile capillary hemangioma
Cavernous hemangioma
Verrucous hemangioma
Lobular capillary hemangioma (pyogenic granuloma)
Arteriovenous hemangioma
Acquired tufted hemangioma
Targetoid hemangioma (hobnail hemangioma)
Fig. 2.8 Capillary hemangioma is characterized by a proliferation of bland

appearing blood vessels in the superficial portion of the dermis. These vessels
may be fully congested with erythrocytes. Original magnification 100×
• Infantile capillary hemangioma

–– Clinical
°° Usually present within days of birth and grow rapidly for

up to a year
°° May involute in up to 75% of cases, usually starting at
about age 5
°° Usually in area surrounding parotid gland, but can grow
to involve airways and to be life-threatening
°° Early lesions – marked cellularity, may have jig-saw

puzzle-like appearance at low magnification
°° Difficult to find vessels – very small
°° Mitoses are abundant
°° Older lesions with less cellularity and more prominent
vessels
• Lobular capillary hemangioma (pyogenic granuloma)
–– Clinical
°° Rapid onset of exophytic red nodule
Fig. 2.9 Juvenile (infantile) capillary hemangioma demonstrates a markedly

cellular proliferation with scattered blood vessels that are often devoid of
erythrocytes. Original magnification 200×
°° Usually ulcerated
°° Most common on fingers, mucous membranes, but can
occur anywhere
°° Increased numbers associated with pregnancy
°° Can occur in any age patient
°° Collarette of rete ridges surrounds proliferation of well-

formed small vessels
°° Feeder vessel at deep margin ramifies into many smaller
vessels
°° Endothelial cell mitoses and mild cytologic atypia may
be present
°° Infiltrate of inflammatory cells most prominent at surface
where ulceration is common
Fig. 2.10 Lobular capillary hemangioma (pyogenic granuloma) is character-

ized by an exophytic proliferation of small blood vessels surrounded by an
epidermal collarette. Original magnification 40×
Fig. 2.11 Lobular capillary hemangioma demonstrates many small blood vessels

with a proliferation of spindle-shaped cells between the vessels. Inflammatory
cells may also be present. Original magnification 200×
• Acquired tufted angioma (angioblastoma)

–– Clinical
°° Benign, progressive angiomatosis most common in chil-

dren and younger adults
°° Slowly enlarging erythematous macules
°° Usually on trunk and upper extremities
°° Cellular lobules dispersed throughout the reticular dermis

°° Ovoid or spindle-shaped cells without atypia
°° Cleft-like luminal spaces
°° Masses of cells protrude into and distort surrounding
thin-walled vessels
• Targetoid hemosiderotic hemangioma
–– Clinical
°° Most common in young to middle-aged men

°° Usually single, on trunk and proximal extremities
°° Central papular area with centrifugal areas of bronze
discoloration
Fig. 2.12 Acquired tufted angioma demonstrates a lobular pattern of dermal

involvement. Original magnification 20×
Fig. 2.13 The lobules consist of angulated blood vessels surrounded by

spindle-shaped cells in acquired tufted angioma. Original magnification 100×

°° Vascular spaces lined by plump endothelial cells with
papillary projections into lumen
°° Abundant hemosiderin deposits, especially laterally
°° Poorly circumscribed and infiltrative growth pattern at
periphery
Fig. 2.14 Targetoid hemosiderotic hemangioma demonstrates thin vessels

with prominent endothelial cells and surrounding hemosiderin. Original
magnification 200×
Fig. 2.15 Targetoid hemosiderotic hemangioma (hobnail hemangioma)

demonstrates prominent endothelial cell protrusion into the lumen in a
hobnail-like pattern. Original magnification 400×
• Lymphangiomas (Table 2.4)
• Lymphangioma circumscriptum
–– Clinical
°° Grouped vesicular papules, often on flank and thighs

°° May appear fluid filled or dark (if hemorrhagic and
thrombosed)
°° Indistinguishable from angiokeratoma except if vessels

are devoid of erythrocytes
°° Epidermal collarette surrounds ectatic vessels in papil-
lary dermis
• Non-hemangiomatous tumors (Table 2.5)
Table 2.4 Lymphangiomas
Lymphangioma circumscriptum
Cystic hygroma
Acquired progressive lymphangioma
Fig. 2.16 Thin-walled vessels, often containing serum but few cells, are present
in the superficial dermis in lymphangioma circumscriptum. There is often an
epidermal collarette. Original magnification 200×
Table 2.5 Non-hemangiomatous tumors
Angiolymphoid hyperplasia with eosinophilia (ALHE)

Spindle cell hemangioendothelioma
Glomus tumor (glomangioma)
Hemangiopericytoma
• ALHE
–– Clinical
°° One or several erythematous papules, nodules
°° Most common around ears and on face
°° Young to middle-aged adults
°° Synonymous with epithelioid hemangioma
–– Histologic (Figs. 2.17–2.19)
°° Abundant small vessels with swollen endothelial cells,
often occluding lumen – difficult to identify as vessels in
some cases
°° Dense inflammatory infiltrate of lymphocytes and eosino-
phils surrounding vascular proliferation
°° Often completely filling dermis, may be germinal centers
present
Fig. 2.17 Angiolymphoid hyperplasia with eosinophilia demonstrates a marked

inflammatory infiltrate at lowest magnification. Original magnification 40×
Fig. 2.18 At high magnification, swollen endothelial cells may make vessels

appear to be small granulomas in angiolymphoid hyperplasia with eosinophilia.
The percentage of eosinophils present in the infiltrate is highly variable.
Original magnification 400×
Fig. 2.19 In some cases of angiolymphoid hyperplasia with eosinophilia,

there are many eosinophils surrounding the thickened blood vessels. Original
magnification 400×
• Spindle cell hemangioendothelioma

–– Clinical
°° May be reactive, and not neoplastic
°° 50% of cases in people <25
°° Single or multiple, but multiple confined to single region
°° Hands and feet most frequent
°° Local recurrence after removal
–– Histologic
°° Three major components
Thin-walled cavernous vessels that may contain thrombi
Solid area of spindle cells with slit-like vascular spaces
(like Kaposi’s sarcoma)
Plump endothelial cells in groups or lining vascular
spaces – intracytoplasmic vacuoles
°° Minimal cytologic atypia or mitotic activity

• Glomus tumor
–– Clinical
°° Erythematous to blue nodules, most common on

extremities
°° Tender/painful
°° Normal blood vessels surrounded by proliferation of
bland, uniform appearing cells with central dark nuclei
and relatively scant cytoplasm
°° Cells express smooth muscle actin
°° “Glomangioma” is variant with concomitant prolifera-
tion of vessels and glomus cells
°° Glomangiosarcoma – very rare
• “Malignant” vascular tumors (Table 2.6)
• Kaposi’s sarcoma
–– Clinical
°° Four subtypes
Classic – men – fifth to seventh decades, E. European
Jews, lower extremities, long chronic course
Fig. 2.20 Glomus tumors are characterized by a proliferation of monomor-

phous, cuboidal cells with small, dark, central nuclei surrounding small blood
vessels. Original magnification 400×
Table 2.6 “Malignant” vascular tumors

Angiosarcoma
Kaposi’s sarcoma
African (endemic) – marked male predominance, can

resemble classic type or involve nodes, also frequent
EBV infection in these patients
Immunosuppressive – younger patients, no male pre-
dominance, tumors appear with treatment and abate
with cessation, more aggressive than classic – may
result in death from GI hemorrhage
HIV associated – intravenous drug abusers and homo-
sexual men, 10% of AIDS patients, widespread lesions,
mucosal involvement, not usually cause of death
°° All associated with HHV-8 infection

°° Patch – irregular vascular spaces surrounding pre-exist-
ing vessels, around appendages, between collagen bun-
dles; lymphocytes and plasma cells
Fig. 2.21 Patch-stage Kaposi’s sarcoma is characterized by a sometimes

subtle proliferation of endothelial cells forming slit-like vascular spaces in the
superficial to mid-dermis. Original magnification 100×
Fig. 2.22 Normal vessels are often surrounded by the slit-like vessels and
increased numbers of endothelial cells in Kaposi’s sarcoma. Extravasation of
erythrocytes is commonly seen. Original magnification 400×
Fig. 2.23 In nodular lesions of Kaposi’s sarcoma, the proliferation of endothelial

cells may be quite dense but there is little cytologic pleomorphism, often despite
brisk mitotic activity. Original magnification 400×
Fig. 2.24 Degenerating erythrocytes may appear as small pink globules

within vessels or in the surrounding dermis in Kaposi’s sarcoma. Original
magnification 600×
°° Plaques and tumors – dermal proliferation of interlacing

bundles of spindle cells and poorly defined vascular
spaces; variable nuclear pleomorphism, rare mitoses,
extravasated erythrocytes, hyaline globules
• Angiosarcoma
–– Clinical
°° Head and neck type

Elderly patients, M > F
Single, blue – violaceous nodules and plaques
15% 5-year survival
°° Arising in lymphedematous limbs (Stewart–Treves)

12.5 years post-surgery
°° Post-irradiation
10–20 years post-irradiation
Fig. 2.25 Angiosarcoma is characterized by a proliferation of angulated,

interanastamosing channels throughout the dermis. The early lesions may be
subtle. Original magnification 100×
Fig. 2.26 The interanastamosing channels are lined by prominent protruding

endothelial cells in angiosarcoma. Original magnification 400×
Fig. 2.27 In some cases, the proliferating endothelial cells may be markedly

spindly in shape. Original magnification 100×
Fig. 2.28 In other cases, the endothelial cells may demonstrate pronounced

atypia and have an epithelioid morphology, making it difficult to determine
the nature of the malignant process. Original magnification 200×
°° Poorly circumscribed proliferation of interanastamosing

vascular spaces
°° Vessels lined with atypical endothelial cells
°° May be solid areas
°° Dense lymphocytic infiltrate in some cases may obscure
vascular proliferation
°° Well-differentiated can resemble benign angiomatous
process, poorly differentiated can be difficult to identify
as vascular
Chapter 3
Histiocytic Proliferations
• Histiocytic proliferations
−− X-histiocytoses – Langerhans cell histiocytoses (LCH)
−− Non-X histiocytoses
• Langerhans cell histiocytosis
−− Letterer–Siwe disease
−− Hand–Schuller–Christian disease
−− Eosinophilic granuloma
−− Congenital self-healing reticulohistiocytosis
−− Indeterminate cell disorder
• Langerhans cell histiocytosis
−− Proliferation of Langerhans cells
−− Distinction between subtypes is not sharp (nor important)
−− Letterer–Siwe
°° Clinical
Infants
Fever, anemia, thrombocytopenia, hepatosplenomegaly,
lymphadenopathy
80% with cutaneous lesions – first sign
Papules and petechiae – may be scaly
Extensive, involving face, scalp, trunk
Resembles seborrheic dermatitis or Darier’s disease
Poor prognosis

DOI: 10.1007/978-3-642-19085-8_3,
60 3 Histiocytic Proliferations
−− Hand–Schuller–Christian disease
°° Clinical
Diabetes insipidus, exophthalmos, bony defects
Other organs may be involved
Cutaneous lesions in about 30% of cases
Plaques with ulceration mainly in mouth, anogenital
region, axillae
Rarely, xanthematous, yellow lesions
May resemble Letterer–Siwe clinically (rare)
30% mortality without treatment
−− Eosinophilic granuloma
°° Clinical
Least severe form
Lesions are few or solitary
Mostly bone lesions, diabetes insipidus may be present
Skin only rarely involved – lesions resemble other
subtypes
Fig. 3.1 Langerhans cell histiocytosis showing a dense papillary dermal

infiltrate of histiocytosis with marked epidermotropism
3 Histiocytic Proliferations 61
Fig. 3.2 The dermal infiltrate in Langerhans cell histiocytosis is accompa-

nied by numerous eosinophils in this case
Fig. 3.3 Langerhans cell histiocytosis showing diffuse expression of CD1a
−− Histologic (Figs. 3.1–3.3)
°° Proliferative lesions
Abundant infiltrate of Langerhans cells close to epider-
mis with marked exocytosis and spongiosis
Cells may be atypical
Variable numbers of eosinophils in infiltrate
°° Granulomatous lesions
Seen with infiltrated plaques
Aggregates of Langerhans cells extending deep into der-
mis and subcutis
Giant cells may be present
Variable numbers of eosinophils
−− Xanthomatous lesions
°° Only in Hand–Schuller–Christian subtype
°° Abundant foam cells seen in conjunction with other
patterns
°° Can also be foreign body or Touton-type giant cells
• Congenital self-healing reticulohistiocytosis
−− Clinical
°° Present at birth or within weeks
°° Multiple scattered papules and nodules
°° Rarely solitary lesion
°° All resolve within 12 months (usually within 2–3)
−− Histologic (Figs. 3.4 and 3.5)
°° Abundant large giant cells with extensive eosinophilic

cytoplasm
°° Can see “ground glass” cytoplasm
°° Admixture of lymphocytes, neutrophils, eosinophils
°° Occasional foam cells
°° Exocytosis and spongiosis
°° Mitotically active
−− Histogenesis
°° Langerhans cell proliferation

°° Cells express CD1 and S100
°° Demonstrate Birbeck granules on electron microscopy
°° Clonality demonstrated in many cases
Fig. 3.4 Congenital self-healing reticulohistiocytosis shows epidermotro-

pism and spongiosis
Fig. 3.5 Giant cells with eosinophilic cytoplasm with “ground glass”
appearance are seen in the dermal infiltrate in congenital self-healing
reticulohistiocytosis
• Indeterminate Cell Proliferative Disorder

−− No characteristic clinical or histologic features
−− Previously regarded as “nodular non-X histiocytosis” or
“generalized eruptive histiocytoma”
−− Dermis filled with S100+, OKT6+ cells that do not contain
Birbeck granules – incompletely developed Langerhans
cells?
• Benign Non-X histiocytoses (Table 3.1)
• Reticulohistiocytosis (multicentric)
−− Clinical
°° Cutaneous nodules associated with polyarthritis
°° Usually in middle-aged women
°° Lasts for about 8 years
°° Destructive arthritis, mostly in interphalangeal joints
°° Skin-colored papules on head and hands
°° 50% with oral lesions
°° Underlying malignancy in 25% of cases, thyroid disease
in 15%, hypercholesterolemia in 33%
°° May be solitary (reticulohistiocytoma) – no systemic
associations
°° Dense infiltrate of multinucleated and mononuclear his-
tiocytes in superficial and mid dermis
°° Histiocytes with pale, ground glass eosinophilic
cytoplasm
Table 3.1 Benign non-X histiocytoses

Juvenile xanthogranuloma (see Chap. 4)
Reticulohistiocytosis (solitary and multiple)
Xanthoma disseminatum
Benign cephalic histiocytosis
Verruciform xanthoma
Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman
disease)
Fig. 3.6 A dense dermal infiltrate fills the superficial reticular and papillary
dermis in reticulohistiocytoma
Fig. 3.7 The infiltrate in reticulohistiocytoma is composed of large cells with

pale, eosinophilic cytoplasm
°° Plasma cells and eosinophils may be present

°° Overlying epidermis thinned
°° Fibrosis in late lesions
°° Cells are S100 negative
• Xanthoma disseminatum
−− Clinical
°° Adult onset
°° Red-brown papules and xanthomatous plaques
°° Symmetrical, flexural surfaces and intertriginous
regions
°° 40% with mucous membrane involvement
°° Normolipemic
°° 40% with diabetes insipidus
°° Good prognosis
°° Dermal histiocytes with foamy cytoplasm
°° Inflammatory infiltrate admixed with occasional
eosinophils
°° Numerous Touton-type giant cells
°° Indistinguishable from JXG histologically
• Benign cephalic histiocytosis
−− Clinical
°° Onset during first 2 years of life
°° M = F
°° Many small yellow-red papules on face, neck, ears
°° Trunk and extremities involved later
°° May regress by age 4 without scarring
°° No systemic anomalies described
−− Histologic
°° Well-demarcated, superficial infiltrate
°° Atrophic epidermis infiltrated with histiocytes
°° Histiocytes with pale, glassy cytoplasm
°° Eosinophils not prominent
°° Cells are S100 negative
°° Comma-shaped bodies in 5–30% of histiocytes on EM
– not specific
Fig. 3.8 The xanthomatous plaques of xanthoma disseminatum show numer-

ous histiocytes in the papillary dermis with a sparse inflammatory infiltrate
consisting of lymphocytes and scattered eosinophils
Fig. 3.9 Multinucleate Touton-type giant cells and cells with abundant
foamy cytoplasm make up the infiltrate in xanthoma disseminatum
• Verruciform xanthoma
−− Clinical
°° Solitary verrucous lesion, most common in oral cavity or
on genitals
°° Also occurs as secondary lesion in association with con-
ditions with marked epidermal hyperplasia (epidermal
nevus, ILVEN)
°° Elongated rete ridges
°° Papillary dermis distended with foam cells pushed up
against the dermal epidermal junction
°° Uniform population of cells – minimal associated
inflammation
• Sinus histiocytosis with massive lymphadenopathy (Rosai–
Dorfman disease)
−− Clinical
°° Benign condition
°° Massive cervical lymphadenopathy
°° 10% of cases with skin involvement
°° Most common site for extranodal disease
°° Multiple papules, nodules
Fig. 3.10 Verruciform xanthoma shows an acanthotic epidermis with elon-

gated rete. There are numerous foamy cells filling the papillary dermal tips
−− Histologic (Figs. 3.12–3.14)
°° Polymorphous dermal infiltrate with many histiocytes,
some with foamy cytoplasm; Touton giant cells
°° Emperipolesis (lymphophagocytosis and erythrophago
cytosis)
Fig. 3.11 The papillary dermal tips in verruciform xanthoma are filled with
cells with abundant foamy cytoplasm
Fig. 3.12 Sinus histiocytosis with massive lymphadenopathy shows a

vaguely nodular dermal dense mixed infiltrate
Fig. 3.13 Higher power of sinus histiocytosis with massive lymphadenopa-

thy shows collections of histiocytosis with foamy cytoplasm accompanied by
a dense lymphohistiocytic infiltrate
Fig. 3.14 Perivascular plasma cells are a characteristic feature of sinus his-

tiocytosis with massive lymphadenopathy
°° Plasma cells collaring blood vessels lined with swollen

endothelial cells
°° Histiocytes are S100+
• Malignant histiocytic proliferations
−− Histiocytic cytophagic panniculitis – better known as subcu-
taneous panniculitis-like T cell lymphoma (at least in the
majority of cases previously diagnosed as histiocytic
cytophagic panniculitis) – see Chap. 1

Chapter 4
“Fibrohistiocytic” Proliferations
• Fibrocytic lesions
–– Scar
°° Normal scar
°° Hypertrophic
°° Keloid
–– Fibrous papule
°° Angiofibroma
• Hypertrophic scar vs. keloid
–– Clinical
°° Initially identical
°° Red, raised plaques with firm surface
°° Hypertrophic scars flatten within years and do not extend
beyond the original scar
°° Keloids persist and enlarge beyond original scar
• Keloid
–– Clinical
°° Familial predisposition
°° More common in African American than Caucasian
population
°° Rubinstein–Taybi syndrome – spontaneous keloids dur-
ing adolescence associated with microcephaly, mental
retardation, breaking of nose, broadening of terminal
phalanges of thumbs and great toes
DOI: 10.1007/978-3-642-19085-8_4,
74 4 “Fibrohistiocytic” Proliferations
°° Hypertrophic scar vs. keloid: spectrum on microscopy

°° Whorls and nodules of thickened collagen bundles –
scant in hypertrophic scar, majority in keloids
°° Collagen bundles are thickened, more hyalinized
°° May be perpendicular to skin surface – unusual in normal
scar formation or in unaffected dermis
• Fibrous papule (Table 4.1)
• Fibrous papule of the nose
–– Clinical
°° Most common on nose, but can occur anywhere (mainly

face)
°° Almost always single
°° Dome-shaped, skin-colored papule up to about 5 mm
Fig. 4.1 Hypertrophic scar shows a dense collagen deposition in the dermis

4 “Fibrohistiocytic” Proliferations 75
Fig. 4.2 Hypertrophic scar on higher power shows the thickened collagen
bundles arranged in haphazard array
Fig. 4.3 Keloid, similar to hypertrophic scar, shows dense collagen deposition.

However the collagen is thick and eosinophilic
Fig. 4.4 This higher power image of keloid shows the comparison of the thick
eosinophilic collagen compared to the adjacent normal dermal collagen
Table 4.1 Variants of fibrous papule
Fibrous papule of the nose

Angiofibroma (adenoma sebaceum)
Pearly penile papule
Subungual fibroma (Koenan’s tumor)
°° Papillary dermal fibrosis (appears as if reticular dermal

collagen is overgrowing the papillary dermis)
°° Concentric perifollicular fibrosis
°° Ectatic blood vessels
°° Stellate fibroblasts
°° Occasionally slight increase in overlying epidermal
melanocytes
°° Dermal dendritic cells express factor XIIIa
• Angiofibroma
–– Histologically identical to fibrous papule
–– Part of tuberous sclerosis constellation
Fig. 4.5 Fibrous papule is composed of ecstatic superficial dermal vessels with

concentric collagen deposition around the follicle and in the papillary dermis
Fig. 4.6 Many fibroblasts in the dermis of a fibrous papule show stellate forms
–– Tuberous sclerosis
°° Autosomal dominant
°° Triad of mental retardation, epilepsy, and angiofibromas
(adenoma sebaceum)
°° May also see fibromas of face, scalp, subungium

°° Shagreen patches – collagenomas
°° Ash-leaf macules – often earliest manifestation (at birth
or shortly thereafter)
Ash leaf macules – normal numbers of melanocytes with
decreased melanin production
°° Gliomas (calcified) in brain and retina

°° Rhabdomyomas of heart
°° Angiomyolipomas of kidneys (tend to be bilateral)
• Pearly penile papule
–– 1–2 mm papules along corona of penis
–– Histologically identical to angiofibroma/fibrous papule of
the nose
• Miscellaneous fibrous conditions
–– Fibrous hamartoma of infancy
–– Acquired digital fibrokeratoma
–– Recurrent infantile digital fibroma
–– Myofibromatosis
–– Nodular fasciitis
• Fibrous hamartoma of infancy
–– Clinical
°° Presents within a year of birth

°° Slight male predominance
°° Occurs on shoulders, axilla, upper arm
°° Rapidly growing 3–5 cm nodule
°° Poorly circumscribed proliferation with three components

Cellular fibrous tissue with spindle-shaped fibroblasts
arranged in an organoid pattern
Loosely arranged bundles of collagen with rounded, imma-
ture appearing fibroblasts resembling neural tissue
Variable amounts of mature fat cells
Fig. 4.7 Fibrous hamartoma of infancy is composed of a poorly circumscribed

proliferation of fibroblasts and mature fat cells
Fig. 4.8 This section of fibrous hamartoma of infancy shows a cellular fibro-

blast proliferations surrounded by loosely arranged collagen and immature
fibroblasts resembling neural tissue admixed with mature fat
Fig. 4.9 Both the cellular and less cellular areas of fibrous hamartoma of
infancy are composed of spindled cells lacking significant atypia and mitoses
• Acquired digital fibrokeratoma

–– Clinical
°° Solitary, round, firm, hyperkeratotic projection on finger
or toe (rarely palm or sole)
°° Usually in adults
°° Differential diagnosis of supernumerary digit
°° Hyperkeratosis, acanthosis
°° Thick, interwoven bundles of collagen oriented perpen-
dicular to skin surface
°° Only thin, scant elastic tissue fibers persist
°° Loss of cutaneous appendages
• Recurrent infantile digital fibroma
–– Clinical
°° Single or multiple nodules on fingers or toes
°° Usually occur during first year of life or rarely later in
childhood
°° Rarely exceed 2 cm in diameter
°° 75% recur during childhood
Fig. 4.10 Acquired digital fibroma shows acanthotic acral-type skin with a
vaguely papillomatous epithelium. Lack of adnexal structures and thick
collagen in bundles perpendicular to the surface are seen in this lesion
°° Numerous spindle-shaped cells in dermis

°° Collagen in interlacing bundles – may extend into
subcutis
°° Eosinophilic cytoplasmic inclusion bodies in fibroblasts
– often perinuclear
°° Inclusions resemble erythrocytes – best seen with
Masson’s (purple) or phosphotungstic acid-hematoxylin
(PTAH) (deep red)
–– Immunostains
°° Stains with smooth muscle actin antibodies

°° Cells are myofibroblasts
°° Infantile digital myoblastoma has been suggested as a
name for these tumors
Fig. 4.11 Recurrent infantile digital fibroma shows a dermal spindle cell
proliferation
Fig. 4.12 Interlacing fascicles of fibroblasts is present in the dermis of this

recurrent infantile digital fibroma
Fig. 4.13 Eosinophilic perinuclear cytoplasmic inclusions (arrows) are

characteristic of recurrent infantile digital fibroma
• Myofibromatosis
–– Clinical
°° Superficial – nodules confined to skin, subcutis, skeletal

muscles, and bone – good prognosis
°° Generalized – visceral nodules obstruct vital organs –
80% mortality within first few months
°° Nodules appear at birth and continue to appear
°° Spontaneous involution of superficial and deep lesions
within first year
°° Well-circumscribed proliferations of spindle-shaped cells

without atypia
°° Arranged in short fascicles
°° Collagen not abundant, areas with mucoid stroma
°° Virtually all cells are myofibroblasts
• Nodular fasciitis
–– Clinical
Fig. 4.14 Myofibromatosis is composed of a relatively well-circumscribed

nodule of short fascicles of spindled cells, lacking atypia
°° Most common in young adults (10–50)

°° Male = female incidence
°° Most common on forearm, but can occur anywhere
°° 75% with rapidly growing lesion (<4 weeks)
°° Tenderness may be present
°° History of trauma in minority
°° Nodules, usually <3 cm
°° Do not recur, even if incompletely excised
°° Occur in subcutis or fascia – subcutaneous ones are well-

circumscribed
°° Spindle, plump, or stellate fibroblasts with vesicular nuclei
and prominent nucleoli – some multinucleated cells
°° Vaguely storiform pattern with myxoid matrix
°° Proliferation of small capillaries and intermixed inflam-
matory cells
°° Zones with increased cellularity
°° 1–2 mitoses/HPF in myxoid areas – no atypical ones
Fig. 4.15 A hypercellular area of nodular fasciitis showing scattered mitoses

and myxoid stroma
Fig. 4.16 A less cellular area of nodular fasciitis showing plump and stellate
fibroblasts
–– Variants (Figs. 4.17 and 4.18)
°° Proliferative fasciitis – abundant giant cells

°° Proliferative myositis – intramuscular analog
°° Cranial fasciitis – infants and children, on scalp
Fig. 4.17 Proliferative fasciitis shows areas of increased cellularity, as in

nodular fasciitis
Fig. 4.18 Numerous large cells with abundant eosinophilic cytoplasm, resem-

bling ganglion cells, are seen in proliferative fasciitis
Table 4.2 Benign Fibrohistiocytic proliferations
Dermatofibroma
Sclerotic fibroma
Fibrous histiocytoma
Angiomatoid variant of fibrous histiocytoma
Juvenile xanthogranuloma
Giant cell tumor of tendon sheath
Atypical fibroxanthoma
°° Paraosteal fasciitis – arises from periosteum of long

bones
°° Intravascular fasciitis – arises from walls of small- to
medium-sized arteries and veins
• Benign fibrohistiocytic proliferations (Table 4.2)
• Dermatofibroma
–– Clinical
°° Single or multiple red-brown indurated nodules

°° Usually in adults
°° Mostly on extremities
°° Characteristic dimpling sign
°° Rare on palms or soles
°° May persist or rarely involute
°° Epidermal hyperpigmentation and elongation of rete

ridges in 80% of cases
°° Spindle-shaped cells coursing singly between collagen
bundles
°° Storiform pattern
°° Poorly demarcated
°° Clumped collagen (appears keloidal) at periphery
°° Located in central reticular dermis, may extend into septa
of subcutis
°° Often a Grenz zone
°° Paucicellular in center of lesion, more cellular at periph-
ery in well-developed lesions
Fig. 4.19 Dermatofibroma showing a cellular dermal infiltrate with an overly-

ing grenz zone and epithelial hyperplasia with increased basilar pigmentation
Fig. 4.20 The cellular infiltrate of a dermatofibroma intercalates and traps

collagen fibers at the periphery of the infiltrate
Fig. 4.21 Cytologic atypia and mitoses may be seen in dermatofibroma
Fig. 4.22 Large multinucleated cells, such as these, may be seen in dermato-

fibroma
°° Occasional “monster” cells (large multinucleated) in

atypical dermatofibromas
°° Old lesions may be fibrotic, much less cellular
• Sclerotic fibroma
–– Clinical
°° Controversial if this entity is distinct from sclerotic

dermatofibroma
°° Associated with Cowden’s syndrome
°° Firm, dome-shaped, skin-colored papule
°° Usually 3–5 mm
°° Dermal nodule comprised of thick bands of hypereo-

sinophilic, thickened collagen bundles in whirled
pattern
°° Also known as “plywood” fibroma referring to micro-
scopic appearance
°° Slight increase in dermal fibroblasts
Fig. 4.23 Sclerotic fibroma shows paucicellular collagen deposition in a pat-

tern reminiscent of wood grain
• Fibrous histiocytoma
–– Probably identical tumor to dermatofibroma
–– No distinct clinical features
–– Increased numbers of histiocytes, often lipid-laden
–– Multinucleated cells common
• Angiomatoid fibrous histiocytoma

–– Clinical
°° Intermediate biologic potential

°° Extremities of children and young adults
°° Slowly growing
°° Recurrence may occur
°° 1% metastasize
°° Unencapsulated, well-circumscribed
°° Spindled to ovoid cells
°° Blood-filled cavernous spaces
Fig. 4.24 Angiomatoid fibrous histiocytoma is a well-circumscribed

proliferation of spindle and ovoid cells in the deep dermis
Fig. 4.25 Cavernous blood-filled spaces are characteristically seen in

angiomatoid fibrous histiocytoma along with a lymphoplasmacytic inflamma-
tory infiltrate
Fig. 4.26 Cytologic atypia and mitoses in angiomatoid fibrous histiocytoma

are not associated with biologic behavior
°° A mild to brisk lymphoplasmacytic infiltrate may also be

present.
°° Pleomorphism and mitoses may be seen, but not associ-
ated with behavior
• Juvenile xanthogranuloma
–– Clinical
°° Often in children, but can occur at any age. Hence the
proposal to drop “juvenile” from the name.
°° 30% present at birth
°° 2–5 mm red-yellow papules
°° May be multiple, retro-orbital
°° Unclear if this entity is extensively lipidized variant of
fibrous histiocytoma or has some other pathogenesis
°° May be associated with neurofibromatosis and café-au-
lait macules
°° Superficial reticular dermal accumulation of histiocytes
°° Many Touton giant cells with lipid at periphery of
cytoplasm
Fig. 4.27 (Juvenile) xanthogranuloma is a polygonal infiltrate in the superfi-

cial dermis
Fig. 4.28 Many Touton-type multinucleate cells are seen at the periphery of

(juvenile) xanthogranuloma
Fig. 4.29 Partially and completely lipidized cells are typically seen in (juve-
nile) xanthogranuloma
°° Admixed lymphocytes and eosinophils in most cases

°° Early lesions may not display Touton giant cells (or lipid)
°° Late lesions – mainly fibrotic
°° Histiocytes are S100 negative
• Giant Cell Tumor of Tendon Sheath (GCTTS)
–– Clinical
°° Subcutaneous nodule attached to tendinous sheath of
fingers, hands, wrists
°° 1–3 cm
°° Relatively asymptomatic
°° Benign
°° Accumulation of histiocytes with intracellular lipid

°° Osteoclast-like giant cells – usually abundant
°° Hemorrhage and hemosiderin often present
Fig. 4.30 Giant cell tumor of tendon sheath shows a proliferation of polygo-

nal cells with bland nuclei extending from a fibrous band or tendon
Fig. 4.31 Numerous multinucleate osteoclast-like giant cells may be seen in

giant cell tumor of tendon sheath. Hemosiderin is also present in this case
• Atypical fibroxanthoma (AFX)

–– Clinical
°° Head and neck of elderly patients
°° More common in men
°° Rarely occur in sites of previous x-ray therapy
°° Probably histogenetically related to fibrous histiocytoma
°° Do not metastasize if truly confined to dermis
°° Very cellular tumor extends up to overlying epidermis,

may ulcerate
°° Markedly pleomorphic, atypical cells – resemble both
fibroblasts and histiocytes
°° Centered in upper half of reticular dermis
°° Abundant mitoses
°° Label with histiocyte markers and focally with smooth
muscle actin
Fig. 4.32 Atypical fibroxanthoma shows a pleomorphic spindle and polygo-

nal cell infiltrate in the dermis, abutting the overlying epidermis
Fig. 4.33 Numerous mitoses, including atypical forms, are seen in atypical
fibroxanthoma
Fig. 4.34 Striking pleomorphism and variably lipidized cells characterized

atypical fibroxanthoma
• Malignant fibrohistiocytic proliferations

–– Dermatofibrosarcoma protuberans (DFSP)
–– Malignant fibrous histiocytoma
• Dermatofibrosarcoma protuberans
–– Clinical
°° Slowly growing, indurated plaque with nodular component

°° May ulcerate
°° Most common on trunk, then extremities
°° Rare on scalp, neck, face; not reported on palms and soles
°° 10% in children – has been reported as congenital
°° 5% of cases metastasize, an average of 6 years post initial
excision
Fig. 4.35 Dermatofibrosarcoma protuberans is composed of a bland dermal

spindle cell proliferation extending into the subcutaneous tissue
°° Resembles “grade 0 fibrosarcoma”

°° Uniform population of spindle cells with minimal colla-
gen formation
°° Grow in storiform pattern
°° More cellular than dermatofibroma, but minimal cyto-
logic atypia
Fig. 4.36 The spindle cells in dermatofibrosarcoma protuberans intercalate

around individual adipocytes in the subcutaneous tissue
°° Mitoses relatively slight

°° Extension into fat lobules (not just septa)
°° May de-differentiate with foci of frank fibrosarcoma
°° Tumor cells express CD34
• Malignant fibrous histiocytoma (MFH) (Figs. 4.37–4.39)
–– Unclear if this tumor exists or is simply an undifferentiated
malignant mesenchymal neoplasm
–– Most common on thighs and buttocks
Fig. 4.37 Malignant fibrous histiocytoma shows a dermal tumor with striking

cytologic atypia
Fig. 4.38 Areas of malignant fibrous histiocytoma show fascicles of spindled

cells with striking pleomorphism and mitoses
Fig. 4.39 Some areas of malignant fibrous histiocytoma show polygonal cells

with striking atypia, multinucleation, mitoses, and lipidization
–– Same histologic features as atypical fibroxanthoma, but

extends deep into dermis and subcutis
–– Subcutaneous tumors – 65% 5 year survival
–– Deeper tumors – 40% 5 year survival
–– Metastasize to lungs and regional nodes
Chapter 5
Tumors of Fat, Nerve,
and Smooth Muscle
• Adipocytic tumors (Table 5.1)

• Lipoma
–– Clinical
°° Most common on trunk and upper extremities

°° Usually in middle-aged to elderly patients
°° 1–4 cm asymptomatic nodules
°° Associated syndromes:
Madelung’s disease – benign symmetric lipomatosis
Dercum’s disease – adiposis dolorosa – multiple painful
lipomas
Familial multiple lipomatosis
–– Histologic features (Fig. 5.1)
°° Sheets of encapsulated fat separated by thin fibrous septa

°° Adipocytes are fully mature cells
°° Mitoses are not apparent
°° No lipoblasts or cellular atypia
°° Lipomas often display cytogenetic abnormalities in
12q13-15
• Angiolipoma
–– Clinical
°° Earlier onset than lipomas

°° Painful
DOI: 10.1007/978-3-642-19085-8_5,
104 5 Tumors of Fat, Nerve, and Smooth Muscle
Table 5.1 Tumors of adipose tissue
Lipoma
Angiolipoma
Spindle cell lipoma
Pleomorphic lipoma
Liposarcoma
Fig. 5.1 Lipoma demonstrates an encapsulated proliferation of mature

adipocytes. Original magnification 100×
°° No associated cytogenetic abnormalities

°° Subcutaneous nodules
°° Encapsulated aggregates of mature adipocytes

°° Variable numbers of clustered, well-formed blood vessels
°° Thrombosed vessels commonly found
• Spindle cell lipoma
–– Clinical
°° Occurs on shoulders and back

°° Mainly in middle-aged men
5 Tumors of Fat, Nerve, and Smooth Muscle 105
Fig. 5.2 Angiolipoma has an admixture of small blood vessels (many of which

may be thrombosed) and mature adipocytes. Original magnification 100×
°° Slowly growing, asymptomatic subcutaneous nodules

°° Tumors demonstrate monosomy 16 or partial loss of 16q
°° Circumscribed, but not encapsulated

°° Arise in subcutis, usually
°° Mixture of mature adipocytes and spindle cells
°° Spindle cells poorly organized
°° Minimal nuclear pleomorphism
°° Mitoses not abundant
°° Lipoblasts NOT seen
°° Spindle cells express vimentin, CD34
• Pleomorphic lipoma
–– Clinical
°° Subcutaneous nodules usually on shoulders, back

°° Up to 5 cm in diameter
°° Most common in elderly men
°° Loss of 16q, similar to spindle cell lipomas
Fig. 5.3 Spindle cell lipoma may demonstrate minimal fat differentiation and
is characterized by “ropey” collagen. Original magnification 200×
°° Circumscribed growth of adipocytes, spindle-shaped

cells, collagen and myxoid matrix
°° Multinucleated giant cells and lipoblasts present
°° “Floret” cells (overlapping nuclei) are characteristic
°° Rare mitoses
°° Spindle cells express CD34 and/or factor XIIIa
• Liposarcoma
–– Debatable if these occur in the skin
–– Semantic – tumors with the appearance of liposarcomas in the
skin do not metastasize so many advocate avoiding this term
–– May extend into subcutis from deeper tissues – mainly in
thighs and buttocks
• Neural tumors (Table 5.2)
• Traumatic neuroma
–– Clinical
°° Results from severing of a nerve

°° Occurs at sites of trauma and in scars
Fig. 5.4 Pleomorphic lipoma demonstrates large, atypical cells that may
resemble lipoblasts. Original magnification 200×
Fig. 5.5 Multinucleated forms and atypical adipocytes are present throughout

pleomorphic lipoma. Original magnification 400×
Table 5.2 Neural tumors
Traumatic neuroma
Neurofibroma
Schwannoma (neurilemmoma)
Palisaded encapsulated neuroma
Myxoid neurothekeoma
Cellular neurothekeoma
°° Firm, oval nodules in subcutis or deeper

°° Often painful
°° Irregular proliferation of nerve bundles surrounded by

fibrosis
°° May resemble onion skins with concentric circles of
nerves and fibrous tissue
°° Multiple axons present in these bundles
• Neurofibroma
–– Clinical
°° Solitary or multiple skin-colored papules

°° More common on upper trunk
Fig. 5.6 Traumatic neuroma demonstrates lobulated whorls of neural

elements. Original magnification 100×
°° Soft and may have “button hole sign” – invagination with

pressure
°° Often do not appear until puberty
°° May be associated with neurofibromatosis, but vast
majority are not
°° NF-1 gene is on long arm of chromosome 17
°° Epidermis often flattened

°° Proliferation of spindle-shaped cells coursing in a light
pink matrix
°° Minimal cytologic atypia
°° Mitoses not apparent
°° Differ from dermatofibromas:
Less eosinophilic stroma
Less nuclear pleomorphism
Lack of epidermal hyperpigmentation and no elongation
of rete ridges
°° “Plexiform” designation used with great caution on cuta-

neous neurofibromas
Fig. 5.7 A proliferation of spindle-shaped cells, often coursing in myxoid

stroma is present within the dermis in neurofibroma. Neurofibromas are not
encapsulated and rarely demonstrates overlying epidermal hyperplasia.
Fig. 5.8 Spindle-shaped cells with tapered ends are present in a myxoid
stroma in neurofibroma. Original magnification 200×
• Schwannoma (neurilemmoma)
–– Clinical
°° Slow growing, usually solitary

°° Up to one-third are painful
°° Usually are 2–4 cm.
°° Can be seen with neurofibromatosis
°° Also occur within viscera
°° Encapsulated dermal proliferations of spindle-shaped cells

°° Cellular areas admixed with more myxoid regions
°° Pseudopalisading regions very characteristic
°° Mitoses very rare
°° No cytologic atypia
• Palisaded encapsulated neuroma (PEN)
–– Clinical
°° Slow-growing painless nodules

°° Usually on face of middle-aged people
Fig. 5.9 Schwannoma demonstrates densely cellular areas admixed with less

cellular areas with myxoid stroma. Original magnification 100×
Fig. 5.10 Verocay bodies with pseudopalisading are characteristic of

schwannomas. Original magnification 100×
°° About 0.5 cm in diameter

°° May be identical to traumatic neuromas
°° Single nodule in dermis

°° Well-developed nerve fascicles coursing in myxoid
stroma
°° No fibrous sheaths like in traumatic neuromas
°° Loose myxoid stroma may cause resemblance to neuro-
fibroma on superficial aspects of tumor nodules
• Neurothekeoma
–– Clinical
°° Most common on face and upper extremities

°° Not associated with neurofibromatosis
°° Two types (histologically):
Myxoid
Cellular
Fig. 5.11 Palisaded encapsulated neuroma is not truly encapsulated, but

demonstrates a sharply circumscribed proliferation of neural elements.
Fig. 5.12 Mature neural elements in a lobulated and whorled pattern

c haracterize palisaded encapsulated neuroma. Original magnification 100×
°° Myxoid type occur in older aged patients than the cellu-

lar variant
°° Dome-shaped nodules up to 3 cm in diameter
°° Unknown etiology – myxoid may be related to schwan-
nomas; cellular variant still unknown
–– Histologic features
°° Myxoid (Figs. 5.13 and 5.14)

Multilobulated, not encapsulated
Located in reticular dermis and may extend into subcutis
Spindle-shaped and stellate cells in swirling pattern
Concentric layering
Myxoid stroma
°° Cellular (Fig. 5.15)
Nests and fascicles in multilobular pattern
Hyalinized stroma between lobules
Concentric pattern to nests of cells
Mitoses may be present
Cells may be hyperchromatic
Fig. 5.13 Myxoid neurothekeoma is characterized by lobules of mucin

containing spindled and epithelioid cells. Original magnification 40×
Fig. 5.14 Myxoid neurothekeoma demonstrates large pools of mucin contain-

ing cells that are not easily characterized based upon morphology. Original
magnification 100×
Fig. 5.15 Cellular neurothekeoma is characterized by lobules of spindled

cells with ample eosinophilic cytoplasm. It is difficult to classify the
nature of the cells on routine histologic sections. Original magnification
200×
–– Immunostains
°° Myxoid
S100 (and vimentin) positive
EMA often positive
°° Cellular
S100 negative
May stain with smooth muscle actin and/or neuron-
specific enolase
NKI/C3 (melanocyte marker) also positive sometimes
• Additional neural crest neoplasms
–– Granular cell tumor
–– Meningioma
–– Merkel cell carcinoma (see separate Chapter in volume 3)
• Granular cell tumor

–– Clinical
°° Frequent on tongue and in oral mucosa

°° More common in women
°° More common in non-Caucasians
°° Usually arise in fifth to sixth decades but can appear in
children
°° Asymptomatic, skin-colored nodules up to 2 cm
°° 10% multiple
°° Multiple rarely associated with neurofibromatosis
°° 1–3% malignant – >5 cm, vascular invasion, necrosis,
rapid growth
°° Pseudoepitheliomatous hyperplasia
°° Sheets of large cells with abundant, eosinophilic, granu-
lar cytoplasm
°° Granules are PAS+, diastase resistant
°° Displace dermal stroma and surround dermal appendages
Fig. 5.16 Granular cell tumor demonstrates sheets of large cells with abun-
dant granular cytoplasm throughout the dermis, with overlying epidermal
hyperplasia. Original magnification 200×
Fig. 5.17 The cytoplasm is eosinophilic and contains prominent granules in

cells that comprise a granular cell tumor. Original magnification 400×
–– Immunohistochemistry
°° Almost always strongly and diffusely S100+

°° Also stain with PGP9.5 (neural) and NKI/C3
°° Negative for myoglobin and glial fibrillary acidic protein
(GFAP)
• Meningioma
–– Clinical
°° Scalp, forehead, and paravertebral

°° May be present at birth or appear in adulthood
°° Rarely associated with neurofibromatosis
°° Involve subcutis and less commonly dermis

°° Irregular strands of meningothelial cells set in fibrous
stroma
°° May also have cellular whorls and even psammoma
bodies
Fig. 5.18 Meningioma is characterized by a lobular proliferation of banal

appearing epithelioid and spindle-shaped cells with ample cytoplasm and the
occasional psammoma body (see arrow). Original magnification 400×
• Malignant neural neoplasms

–– Malignant peripheral nerve sheath tumor
• Malignant peripheral nerve sheath tumor
–– Previously known as neurosarcoma, neurofibrosarcoma,
malignant schwannoma
–– Rare
–– Probably arise from malignant transformation of
neurofibromas
–– > 50% of patients with this tumor have neurofibromatosis
–– 2–3 year mean survival
°° Spindle cell proliferation with wavy bundles

°° Alternating areas of dense cellularity with more myxoid
areas
°° Can be cellular with abundant mitoses and pleomorphism
°° Can show divergent differentiation with other sarcoma-
tous elements
°° Express S100, neuron-specific enolase, neurofilament
Fig. 5.19 Malignant peripheral nerve sheath tumor demonstrates a spindle

cell proliferation with abundant, pleomorphism and bizarre, atypical forms.
• Smooth muscle proliferations

–– Smooth muscle hamartoma
–– Leiomyoma
°° Angioleiomyoma
°° Piloleiomyoma
–– Leiomyosarcoma
• Smooth muscle hamartoma
–– Clinical
°° May present with hyperpigmented patch with irregular

surface
°° Poorly circumscribed, diffuse proliferation of perfectly

mature smooth muscle bundles
°° Usually localized to superficial portion of reticular
dermis
°° No mitotic activity of cytologic atypia

°° Often associated with enlarged terminal hairs and epi-
dermal hyperplasia and hyperpigmentation (Becker’s
nevus)
• Leiomyoma
–– Clinical
°° Occasionally painful/tender dermal nodule with overly-

ing hyperpigmentation and superficial dimpling (pseudo-
Darier’s sign)
°° Most common on extremities
°° Poorly circumscribed, diffuse proliferation of perfectly

mature smooth muscle bundles
Fig. 5.20 Leiomyoma is characterized by a proliferation of eosinophilic fas-

cicles coursing in bundles throughout the dermis. Original magnification 40×
Fig. 5.21 Spindle-shaped cells coursing in fascicles, with little nuclear atypia

or pleomorphism characterize leiomyoma. Original magnification 400×
°° Usually more cohesive and circumscribed than smooth

muscle hamartoma, but often difficult to distinguish
based on histologic changes
–– Angioleiomyoma
°° Bundles of smooth muscle (eosinophilic with “cigar

shaped nuclei”) surrounding large dermal blood vessel
°° Usually in deeper dermis
°° Well circumscribed
°° Mitoses infrequent
–– Piloleiomyoma
°° Bundles of smooth muscle more diffusely scattered

throughout the superficial portion of the reticular dermis
°° Not obviously centered around arrector pili muscles
°° Mitoses infrequent
Fig. 5.22 Leiomyosarcoma demonstrates marked nuclear pleomorphism,

bizarre atypical forms, and abundant mitoses within the proliferation of
smooth muscle cells
• Leiomyosarcoma
°° Controversial as these tumors rarely, if ever, metastasize

when dermally based
°° De-differentiation with recurrence of leiomyoma has
been reported
°° Infiltrative growth pattern
°° Bundles of smooth muscle cells demonstrating nuclear
pleomorphism
°° Abundant mitoses (exact numerical requirement not as
clearly defined as leiomyosarcomas in other organs)
°° Necrosis may be present (unlike in leiomyomas)
Chapter 6
Cutaneous Metastases
• Carcinoma metastatic to the skin (Tables 6.1 and 6.2)

–– Occurs in 0.7–9.0% of all patients with cancer
–– Most frequent sites on the body for metastases to appear:
°° At sites of incision of primary tumors

°° Three-fourths of metastases are on head and neck,
despite only one-fourth surface area
°° Extremities uncommon site for metastases
–– Most common presentation is that of a painless, skin-colored,
freely mobile cutaneous nodule; ulceration uncommon
–– Indurated plaques, erysipelas-like patterns also seen
–– Survival: 1–34 months following identification of cutaneous
metastasis
–– One-third of patients develop cutaneous metastases within
6 months of initial diagnosis
–– One-half develop metastases within 1 year of initial diagno-
sis and >90% within 5 years
• Metastatic breast carcinoma
–– Clinical
°° Seen in 23.9% of patients with breast carcinoma

°° Presenting sign in 3.5% of such patients
°° Different clinical patterns: inflammatory (resembles erysipe-
las), en cuirasse (resembles morphea), telangiectatic pattern,
nodular metastases, alopecia neoplastica, Paget’s disease

DOI: 10.1007/978-3-642-19085-8_6,
124 6 Cutaneous Metastases
Table 6.1 Most common carcinomas metastatic to skin in women
Most frequent primary sources Percent of total cutaneous

in women metastases in women
Breast 69
Colon 9
Melanoma 5
Lung 4
Ovary 4
Table 6.2 Most common carcinomas metastatic to skin in men
Most frequent primary sources Percent of total cutaneous

in men metastases in men
Lung 24
Colon 19
Melanoma 13
Oral squamous cell carcinoma 12
Stomach 6
Kidney 6
Esophagus 3
°° Inflammatory – tumor cells confined largely to dermal

lymphatics
°° Telangiectatic tumor altering blood flow leads to widely
dilated and congested blood vessels
°° Alopecia neoplastic – blood vascular spread to scalp
°° Nodular-type most likely to be confused with primary
eccrine adenocarcinoma
°° May be separate nodules or diffusely infiltrating entire dermis
°° Atypical cells prominent at low magnification
°° Ductular differentiation may be present
• Metastatic renal cell carcinoma
–– Clinical
°° Hemorrhagic tumor nodule

°° Scalp is most common site (28% of cases)
6 Cutaneous Metastases 125
Fig. 6.1 Inflammatory breast carcinoma shows dermal lymphatics distended

with tumoral cells
Fig. 6.2 Metastatic lobular breast carcinoma shows individual tumor cells in

a single file infiltrating between collagen bundles
Fig. 6.3 Cutaneous metastasis of ductal breast carcinoma shows nodules of

tumor cells with ductal differentiation
Fig. 6.4 The ductal differentiation in metastatic ductal carcinoma can be so

extensive as to mimic a primary eccrine carcinoma
°° More common in men

°° Ulceration uncommon
°° Highly vascular neoplasm
°° Clear cytoplasm, some mitoses and cytologic atypia
°° Differential diagnosis includes pyogenic granuloma
which has spindle-shaped cells in surrounding stroma
and less cytologic atypia.
–– Immunohistochemical features
°° RCC stains with EMA and cytokeratin cocktails, as does
pyogenic granuloma
°° RCC often S100 positive
°° RCC stains with renal cell carcinoma antibodies and with
PAX-2
–– Prognosis
°° Metastatic renal cell carcinoma – rarely can spontaneous
regress with cure
°° 5 -year survival with known primary RCC and a single
cutaneous metastasis is 35%
Fig. 6.5 Metastatic renal cell carcinoma is characteristically highly vascular

Fig. 6.6 The tumoral cells of metastatic renal cell carcinoma are often clear,
or vacuolated
• Metastatic neuroendocrine carcinoma

°° Identical to Merkel cell carcinoma (Fig. 6.7)

–– Immunohistochemical features
°° Cytokeratin 20 (and CAM 5.2) stains almost all MCC with

either punctate cytoplasmic pattern or membranous pattern
°° Less frequent, but similar pattern can be seen in neuroen-
docrine carcinomas
°° Thyroid transcription factor 1 – not seen in MCC, present
in most metastatic small cell carcinomas from the lung
and other sources
• Melanoma – primary vs. metastatic
°° Individual lesions may be identical

°° Primary lesions identified in >95% of cases, so history is
crucial
Fig. 6.7 Metastatic neuroendocrine carcinoma is histologically identical to

primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) with
small cells having open chromatin, minimal cytoplasm, and numerous mitoses
°° Multiple lesions favor metastasis over primary

°° Proximal spread along cutaneous lymphatics also helpful
°° Diffuse melanosis another pattern (rare)
°° Usual histology is a dermal nodule, often well-circum-

scribed without epidermal changes
°° Differentiation from primary melanomas usually rela-
tively straightforward
°° Epidermotropic metastatic melanomas recently described
°° Intraepidermal atypical melanocytes do not extend lateral
to the dermal involvement in most cases – some excep-
tions reported
°° Nesting pattern and Pagetoid invasion
°° Inflammatory response often pronounced in these types
of metastases
°° Involvement may be limited to superficial dermis in nest-
ing pattern
°° Small size to these types of lesions also reported
Fig. 6.8 Metastatic melanoma has cytologic features and immunohistochem-

ical staining consistent with melanoma. An in situ component is not present
in the overlying epidermis
°° Often vascular and lymphatic invasion seen

°° May see thinning of epidermis or epidermal hyperplasia
°° Can be seen in lesions <3 mm in diameter
• Metastatic squamous cell carcinoma
°° Usually not the presenting sign of cancer

°° Nodal involvement often present
°° Direct extension from underlying nodes often seen
°° Only diagnostic feature is lack of connection to overlying

epidermis
°° This can be seen with some primary cutaneous lesions
(sampling)
°° May see tumor spreading up to epidermis, making it look
primary
Further Reading
Chapter 1
Lymphoma classification systems
Jaffe ES. The 2008 WHO classification of lymphomas: implica-

tions for clinical practice and translational research. Hematol-
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Kempf W, Sander CA. Classification of cutaneous lymphomas –
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Robson A. Immunocytochemistry and the diagnosis of cutaneous
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Weaver J, Mahindra AK, Pohlman B, Jin T, His ED. Non-mycosis
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Mycosis fungoides
Diwan H, Ivan D. CD8-positive mycosis fungoides and primary

cutaneous aggressive epidermotropic CD8-positive cytotoxic
T-cell lymphoma. J Cutan Pathol 2009; 36: 390–392.
Duvic M, Foss FM. Mycosis fungoides: pathophysiology and
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Heald PW, Kempf W, Knobler R, Lessin S, Sander C, Smoller
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Smoller BR. Mycosis fungoides: what do/do not we know? J Cu-
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el-Azhary RA. Clinical, histopathologic, and immunopheno-
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Kunishige JH, McDonald H, Alvarez G, Johnson M, Prieto V,
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134 Further Reading
Subcutaneous panniculitis-like T cell lymphoma

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Willemze R, Jansen PM, Cerroni L, Berti E, Santucci M, Assaf
C, Canninga-can Dijk MR, Carlotti A, Geerts ML, Hahtola S,
Hummel M, Jeskanen L, Kempf W, Massone C, Ortiz-Romero
PL, Paulli M, Petrella T, Ranki A, Peralto JL, Robson A, Senff
NJ, Vermeer MH, Wechsler J, Whittaker S, Meijer CJ: EORTC
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NK/T cell lymphoma, nasal type
Schwartz EJ, Molina-Kirsch H, Zhao S, Marinelli RJ, Warnke

RA, Natkunam Y. Immunohistochemical characterization
of nasal-type extranodal NK/T-cell lymphoma using a tissue
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Marginal zone lymphoma
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are they different from other extranodal marginal zone B-cell
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Follicular lymphoma
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cutaneous B-cell lymphoma. J Am Acad Dermatol 2005; 53:
479–484.
Kerl H, Cerroni L. Primary cutaneous B-cell lymphomas: then and
now. J Cutan Pathol 2006: 33 (suppl 1): 1–5.
Primary cutaneous B cell lymphoma, leg type
Senff NJ, Willemze R. The applicability and prognostic value of

the new TMN classification system for primary cutaneous lym-
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136 Further Reading
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Puches R, Kerl H, Cerroni L. 9p21 deletion in primary cutaneous
large B-cell lymphoma, leg type, may escape detection by stand-
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Intravascular B-cell lymphoma
Eros N, Karolyi Z, Kovacs A, Takacs I, Radvanyi G, Kelenyi G.

Intravacular B-cell lymphoma. J Am Acad Dermatol 2002; 47
(5 suppl): S260-262.
Kong YY, Dai B, Sheng WQ, Yang WT, Wang CF, Kong JC, Shi
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Chapter 2
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hemangioma and vascular malformations. Facial Plast Surg
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Hereditary hemorrhagic telangiectasia
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Angiokeratoma
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Venous lake
Requena L, Sangueza OP. Cutaneous vascular anomalies. Part I.

Hamartomas, malformations and dilation of preexisting ves-
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Capillary hemangioma
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Infantile hemangioma
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hemangioma and vascular malformations. Facial Plast Surg
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138 Further Reading
Cavernous hemangioma

1997; 37: 887–919.
Tsang WY, Chan JK, Fletcher CD. Recently characterized vascu-
lar tumours of skin and soft tissues. Histopathology 1991; 19:
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Verrucous hemangioma
Tennant LB, Mulliken JB, Perez-Atayde AR, Kozakewich HP.

Verrucous hemangioma revisited. Pediatr Dermatol 2006; 23:
208–215.
Lobular capillary hemangioma

(pyogenic granuloma)
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77–80.
1997; 37: 887–919.
Arteriovenous hemangioma
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1997; 37: 887–919.
Acquired tufted hemangioma
Prieto VG, Shea CR. Selected cutaneous vacular neoplasms. A re-

view. Dermatol Clin 1999; 17: 507–520.
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lar tumours of skin and soft tissues. Histopathology 1991; 19:
489–501.
Targetoid hemangioma (hobnail hemangioma)
Prieto VG, Shea CR. Selected cutaneous vacular neoplasms. A re-

view. Dermatol Clin 1999; 17: 507–520.
1997; 37: 887–919.
Vion B, Frenk E. Targetoid hemosiderotic hemangioma. Derma-
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Lymphangioma circumscriptum
Bauer BS, Kernahan DA, Hugo NE. Lymphangioma circumscriptum—

a clinicopathological review. Ann Plast Surg 1981; 7: 318–326.
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Angiolymphoid hyperplasia with eosinophilia
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140 Further Reading
Spindle cell hemangioendothelioma

1997; 37: 887–919.
Tsang WY, Chan JK, Fletcher CD. Recently characterized vascular tu-
mours of skin and soft tissues. Histopathology 1991; 19: 489–501.
Glomus tumor/glomangioma
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icopathologic and immunohistochemical analysis of six cases with
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Hemangiopericytoma
Fletcher CD, McKee PH. Sarcomas—a clinicopathological guide

with particular reference to cutaneous manifestation. III. Angi-
osarcoma, malignant hemangiopericytoma, fibrosarcoma, and
synovial sarcoma. Clin Exp Dermatol 1985; 10: 332–349.
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Angiosarcoma
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with particular reference to cutaneous manifestation. III. Angio
sarcoma, malignant hemangiopericytoma, fibrosarcoma, and
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Kaposi’s sarcoma
Goh SG, Calonje E. Cutaneous vascular tumours: an update. His-

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Wilkins K, Turner R, Dolev JC, LeBoit PE, Berger TG, Maurer
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Langerhans cell histiocytosis
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dren. Cancer Invest 2009; 27: 504–511.
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Massone L, Kowalski JV, Bhawan J. Langerhans cell histiocy-
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Congenital self-healing reticulohistiocytosis
Kanitakis J, Zambruno G, Schmitt D, Cambazard F, Jacque-

mier D, Thivolet J. Congenital self-healing histiocytosis
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Ricart J, Jimenez A, Marquina A, Villanueva A. Congenital self-
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Indeterminate Cell Proliferative Disorder
Manente L, Cotellessa C, Schmitt I, Peris K, Torlone G, Muda

AO, Romano MC, Chementi S. Indeterminate cell histiocyto-
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Rosenberg AS, Morgan MB. Cutaneous indeterminate cell histio-
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Reticulohistiocytosis (multicentric)
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Lutz FM, Kurizky PS, Ramos-e-Silva M. Retculohistiocytosis.
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Xanthoma disseminatum
Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M,
Bucsky P, Egeler RM, Elinder G, Gadner H, Gresik M, Henter
HI, Imashuki S, Janka-Schaub G, Jaffe R, Ladisch S, Nezelof
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Benign cephalic histiocytosis
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case report and review. J Am Acad Dermatol 2002; 47: 906–913.
Zelger BW, Sidorof A, Orchard G, Cerio R. Non-Langerhans cell
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Verruciform Xanthoma
Nowparast B, Howell FV, Rick GM. Verruciform Xanthoma. A

Clinicopathologic review and report of fifty-four cases. Oral
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Sinus histiocytosis with massive lymphadenopathy

(Rosai-Dorfman disease)
Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive

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Histiocytic cytophagic panniculitis
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Hypertrophic scar
Liu B, Connolly MK. The pathogenesis of cutaneous fibrosis.

Semin Cutan Med Surg 1998; 17: 3–11.
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Keloid
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Fibrous papule
Bansal C, Stewart D, Li A, Cockerell CJ. Histologic variants of

fibrous papule. J Cutan Pathol 2005; 32: 424–428.
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Pearly penile papule
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Fibrous hamartoma of infancy
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Acquired digital fibrokeratoma
Kint A, Baran R. Histopathologic study of Koenen tumors. Are

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Recurrent infantile digital fibroma
Grenier N, Liang C, Capaldi L, Ney A, Lapidus C, Schappell D, Ka-

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Myofibromatosis
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Sclerotic fibroma
Gonzalez-Vela MC, Val-Bernal JF, Martino M, Gonzalez-Lopez

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Fibrous histiocytoma
Billings SD, Folpe AL. Cutaneous and subcutaneous Fibrohis-

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Juvenile xanthogranuloma
Dehner LP. Juvenile xanthogranulomas in the first two decades

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Giant Cell Tumor of Tendon Sheath (GCTTS)
Ciattaglia G, Filossa G, Bugatti L. Giant cell tumor of tendon

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Atypical fibroxanthoma (AFX)
Gleason BC, Calder KM, Cibull TL, Thomas AB, Billings SD,
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Dermatofibrosarcoma protuberans
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Malignant fibrous histiocytoma (MFH)

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Chapter 5
Lipoma
Challis D. Atypical subcutaneous fatty tumors. Adv Anat Pathol

2000; 7: 94–99.
Mentzel T. Cutaneous lipomatous neoplasms. Semin Diagn Pathol
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Angiolipoma
Requena L, Sangueza OP. Cutaneous vascular proliferations. Part

III. Malignant neopalms, other cutaneous neoplasms with sig-
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Spindle cell lipoma
Billings SD, Folpe AL. Diagnosticlaly challenging spindle cell

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Pleomorphic lipoma
Mentzel T. Cutaneous lipomatous neoplasms. Semin Diagn Pathol

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Liposarcoma
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150 Further Reading
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Traumatic neuroma
Argenyi ZB, Santa Cruz D, Bromley C. Comparative light-

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Neurofibroma
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Schwannoma (neurilemmoma)
Reith JD, Goldblum JR. Multiple cutaneous plexiform schwannomas.

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Palisaded encapsulated neuroma (PEN)
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Neurothekeoma
Fetsch JF, Laskin WB, Hallman JR, Lupton GP, Mettinen M.

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Granular cell tumor
Rejgi B, Jambhekar NA. Morphologic spectrum, immunoshisto-

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Meningioma
Hussein MR, Abdelwahed AR. Primary cutaneous meningioma of

the scalp: a case report and review of literature. J Cutan Pathol
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Smooth muscle hamartoma
Holst VA, Junkins-Hopkins JM, Elenitsas R. Cutaneous smooth

muscle neoplasms: clinical features, histologic findings, and
treatment options. J Am Acad Dermatol 2002; 46: 477–490.
Leiomyoma

Smith G, Heidary N, Patel R, Rosenman K, Meehan SA, Kamino
H, Sanchez M. Cutaneous piloleiomyomata. Dermatol Online
J 2009; 15: 10.
Leiomyosarcoma

Hornick JL, Fletcher CD. Crieteria for malignancy in nonvisceral
smooth muscle tumors. Ann Diagn Pathol 2003; 7: 60–66.
Pipe J, Broers GH, Plaat BE, Hundeiker M, Otto F, Mastik MF,
Hoekstra HJ, van der Graaf WT, Berg ED, Molenaar WM. The
relation between histologic, tumor-biological and clinical pa-
rameters in deep and superficial leiomyosarcoma and leiomyo-
ma. Sarcoma 2002; 6: 105–110.
Further Reading 153
Chapter 6
Cutaneous metastases
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Pathol 2010: 37: e1-20.
Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the
presenting sign of internal carcinoma. A retrospective study of
7316 cancer patients. J Am Acad Dermatol 1990; 22: 19–26.
Pipkin CA, Lio PA. Cutaneous manifestations of internal malig-
nancies: an overview. Dermatol Clin 2008; 26: 1–15.
Sariya D, Ruth K, Adams-McDonnell R, Cusack C, Xu X, Elenit-
sas R, Seykora J, Pasha T, Zhang P, Baldassano M, Lessin SR,
Wu H. Clinicopathologic correlation of cutaneous metastases:
experience from a cancer center. Arch Dermatol 2007; 143:
613–620.

Index
A D
Acquired capillary hemangioma, 43 Dermatofibroma, 87, 91
Acquired digital fibrokeratoma, 80 Dermatofibrosarcoma protuberans
Acquired progressive (DFSP), 98–99
lymphangioma, 49
Acquired tufted angioma, 46, 47 E
Acquired tufted hemangioma, 46 Erythroderma, 7
Adenoma sebaceum, 76, 77 Extranodal NK/T cell lymphoma,
Anaplastic large cell lymphoma, 2, 18–20
9–12
Angioblastoma, 46 F
Angiofibroma, 73, 76–78 Fibrous hamartoma of infancy, 78
Angiokeratoma, 39–40 Fibrous histiocytoma, 91
Angioleiomyoma, 121 Fibrous papule, 73, 74
Angiolipoma, 103–104
Angiolymphoid hyperplasia with G
eosinophilia (ALHE), 50–51 Giant cell tumor of tendon
Angiomatoid fibrous histiocytoma, sheath, 95
91–93 Glomangioma, 52
Angiosarcoma, 56–58 Glomus tumor, 52
Angiotropic lymphoma, 33 Granular cell tumor, 115–117
Atypical fibroxanthoma, Granulomatous slack skin, 7
96, 98, 102
H
B Hemangioma, 43
Blastic plasmacytoid dendritic cell Hematodermic neoplasm,
neoplasm. See Hematoder- 2, 20–22
mic neoplasm Hereditary hemorrhagic
Borrelia burgdorferi, 25 telangiectasia, 37
Hypertrophic scar, 73, 74
C
Cranial fasciitis, 86 I
Cystic hygroma, 49 Infantile capillary hemangioma, 44

DOI: 10.1007/978-3-642-19085-8,
156 Index
Intravascular fasciitis, 87 renal cell carcinoma, 124, 127, 128

Intravascular papillary endothelial squamous cell carcinoma, 130
hyperplasia (IVPEH), 41–42 Multinucleate cells, 91, 94, 95, 102
Mycosis fungoides, 2–7
J folliculotropic, 7
Juvenile xanthogranuloma, 93 granulomatous, 7
Myofibromatosis, 83
K Myxoid, 113, 114
Kaposis sarcoma, 52–55
Keloid, 73 N
Koenan tumor, 76 Neurofibroma, 108, 109
Neurothekeoma, 112–115
L Neurothekeoma, cellular, 113–115
Leiomyoma, 120, 121 NK blastic lymphoma. See Hemato-
Leiomyosarcoma, 122 dermic neoplasm
Lipidized cell, 94, 98 Nodular fasciitis, 83–84
Lipoma, 103–105
Liposarcoma, 106 P
Lobular capillary hemangioma Pagetoid reticulosis, 7
(pyogenic granuloma), 45, 46 Palisaded encapsulated neuroma,
Lymphangioma, 49 110, 112
Lymphangioma circumscripta, 49 Paraosteal fasciitis, 87
Lymphoma Pearly penile papule, 78
intravascular B-cell type, 33 Piloleiomyoma, 121
primary cutaneous follicular Pleomorphic lipoma, 105–107
center, 26 Port wine stain, 37–39
primary cutaneous large B-cell Primary cutaneous CD30+ lympho-
lymphoma of the leg, 29 proliferative disorder, 2, 9
Primary cutaneous marginal Proliferative fasciitis, 86
zone, 21 Proliferative myositis, 86
Lymphomatoid papulosis, 12–16 Pyogenic granuloma, 45
M R
Malignant angioendotheliomatosis, Rubenstein–Taybi syndrome, 73
33
Malignant fibrous histiocytoma, S
100–102 Scar, 73
Malignant peripheral nerve sheath Schwannoma (neurilemmoma),
tumor, 118–119 110, 111
Meningioma, 117–118 Sclerotic fibroma, 90
Metastatics Sezary syndrome, 2, 7–8
breast cancer, 123–126 Smooth muscle hamartoma, 119
melanoma, 128, 130 Spindle cell hemangioendothe-
neuroendocrine carcinoma, lioma, 52
128, 129 Spindle cell lipoma, 104, 105
Index 157
Subcutaneous panniculitis-like Telangiectasias, 37

T cell lymphoma, 2, 16–18 Traumatic neuroma, 106, 108
Subungual fibroma, 74 Tuberous sclerosis, 77
T V
Targetoid hemosiderotic Venous lake, 41
hemangioma, 46–48

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Dermal Tumors: The Basics

ISBN 978-3-642-19084-1 e-ISBN 978-3-642-19085-8

Library of Congress Control Number: 2011929931

© Springer-Verlag Berlin Heidelberg 2011

Cover design: eStudioCalamar, Figueres/Berlin

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

In this fourth, and final, volume of the series on dermatopathology

Little Rock, Arkansas, USA Bruce R. Smoller

1 An Overview of Cutaneous Lymphomas . . . . . . . . . 1

• Classifications of cutaneous lymphomas

°° Revised European-American Classification of Lym­

–– WHO 2008 classification

°° 0.42 cases/100,000 population

Table 1.1 T cell lymphomas

Mycosis fungoides/Sezary syndrome

°° Twice as common in African Americans as in Caucasian

°° Epidermotropic proliferation of hyerconvoluted, hyper-

Fig. 1.1 Early lesions of mycosis fungoides show an epidermotropic lympho-

Fig. 1.2 In more evolved lesions of mycosis fungoides, small clusters of

°° Difficult diagnosis to make in early lesions

°° Mycosis fungoides is defined as a neoplastic prolifera-

°° T-cell gene rearrangements seen in 50–80% of patch-

Fig. 1.5 The epidermotropic lymphocytes in mycosis fungoides most

°° Folliculotropic – characteristic morphology; 70–80%

°° Pagetoid reticulosis – localized patches, very epidermo-

(>1,000 cells/mm , CD4/CD8 ratio >10, loss of CD2,

CD3, CD4, and/or CD4)

–– Mean survival 2–4 years

°° Primary cutaneous ALCL occurs primarily in adults

°° One to several nodules or small tumors

Fig. 1.8 Granulomatous mycosis fungoides shows sarcoidal granulomas in

°° <10% with lesions extending beyond one area of skin

°° Dense dermal infiltrate of large lymphocytes with

°° Defined as >75% of cells expressing CD30 in skin

Fig. 1.9 Anaplastic large cell lymphoma shows a dense dermal infiltrate of

°° CD2, CD3, and CD5 may be absent

°° Process may last from weeks up to 40 years

°° Large, atypical CD30+ cells interspersed with a brisk

Fig. 1.12 Lymphomatoid papulosis shows a dense dermal infiltrate (A) with

Fig. 1.13 This case of lymphomatoid papulosis shows an exuberant dermal

°° CD3+, CD4+, CD8−

°° Previously known as histiocytic cytophagic panniculitis

°° Multiple red to violaceous cutaneous nodules

°° Dense, diffuse infiltrate of small to medium-sized lym-

°° All cases represent T cell lymphomas

Fig. 1.15 Subcutaneous panniculitis-like T-cell lymphoma shows a dense,

Fig. 1.16 Rimming of adipocytes by neoplastic T-cells is seen in subcutane-

°° Generally favorable – 5 year survival of 80% with fre-

°° In this case, primary vs. secondary not important for

°° Superficial and deep dermal infiltrates of atypical

Fig. 1.17 Extranodal NK/T-cell lymphoma has a superficial and deep dermal

°° Neoplastic cells often accompanied by heavy mixed

Fig. 1.18 Angiocentric infiltrate with complete necrosis of the vessel is seen

°° Gene rearrangements usually not seen

°° Aggressive chemotherapy (cytoxan, vincristine, adriamy-

°° CD56+ lymphomas have less than 12 month median

–– Similar cells morphologically to NK/T cell lymphoma,

Little Rock, Arkansas, USA Bruce R. Smoller

°° Revised European-American Classification of Lym

Fig. 1.19 CD4+/CD56+ hematodermic neoplasms show a diffuse, non-

• Intravascular B cell lymphoma (malignant angioendothe

Fig. 2.11 Lobular capillary hemangioma demonstrates many small blood vessels