ROUND CELL

TUMORS
Namrata Sengupta
PG (III)
Guided by Dr. Sachin Sarode
Oral Pathology & Microbiology
Presented on: 1st September, 2021
 INTRODUCTION
• Round cell tumors are heterogenous group of malignant
neoplasms, characterised by round and relatively
undifferentiated cells.

• Diagnosis of these tumors is difficult and imposes a challenge

for pathologists due to their undifferentiated or primitive
character.

• Thus, differentiating these tumors with others still remains

enigmatic.
• Cytologically, these tumors are composed of a nearly uniform
population of round to oval cells with scanty, basophilic
cytoplasm.

• These are also called round blue cell tumors as the cells
appear blue due to presence of large hyperchromatic nuclei and
a thin rim of cytoplasm.

• Show round cells with increased nuclear-cytoplasmic ratio.

• Malignant round cells in these tumors may be small or large in
size.

• Small round cells have diameters up to approximately three

times that of a small mature lymphocyte whereas large round
cell have diameter approximately 4-5 times that of mature
lymphocytes.
 CLASSIFICATION
• Although, various authors have elaborated their discussion on
round cell tumours; however, there is no accepted working
classification for round cell tumors of the oral cavity in the
literature.
Sharma S, Kamala R, Nair D, Ragavendra TR, Mhatre S, Sabharwal R, Choudhury BK, Rana V. Round Cell Tumors: Classification and
Immunohistochemistry. Indian J Med Paediatr Oncol. 2017 Jul-Sep;38(3):349-353. doi: 10.4103/ijmpo.ijmpo_84_16. PMID: 29200688;
PMCID: PMC5686981.
Sharma S, Kamala R, Nair D, Ragavendra TR, Mhatre S, Sabharwal R, Choudhury BK, Rana V. Round Cell Tumors: Classification and
Immunohistochemistry. Indian J Med Paediatr Oncol. 2017 Jul-Sep;38(3):349-353. doi: 10.4103/ijmpo.ijmpo_84_16. PMID: 29200688; PMCID:
PMC5686981.
Sharma S, Kamala R, Nair D, Ragavendra TR, Mhatre S, Sabharwal R, Choudhury BK, Rana V. Round Cell Tumors: Classification and
Immunohistochemistry. Indian J Med Paediatr Oncol. 2017 Jul-Sep;38(3):349-353. doi: 10.4103/ijmpo.ijmpo_84_16. PMID: 29200688; PMCID:
PMC5686981.
Sharma S, Kamala R, Nair D, Ragavendra TR, Mhatre S, Sabharwal R, Choudhury BK, Rana V. Round Cell Tumors: Classification and
Immunohistochemistry. Indian J Med Paediatr Oncol. 2017 Jul-Sep;38(3):349-353. doi: 10.4103/ijmpo.ijmpo_84_16. PMID: 29200688;
PMCID: PMC5686981.
 Round cell tumors of the oral cavity

Gupta R.et al. Round cell tumors of the oral cavity: an insight on salient features for oral and
maxillofacial pathologists. Int J Dent Health Sci 2016; 3(6):1107-1119.
Gupta R.et al, Int J Dent Health Sci 2016; 3(6):1107-1119
 Ewing’s Sarcoma
• Ewing's sarcoma is a sarcoma of bone classically described under small round cell
tumors.

• Hematoxylin-eosin staining (HE) defines ES as belonging to the group of small blue

round cell tumors - a series of very aggressive tumors with a high incidence in
children and adolescents.

• The periodic acid-Schiff technique (PAS), which stains carbohydrates red, is usually
positive in ES, revealing the presence of intracellular glycogen granules, which help
differentiate the disease from tumors of neural lineage. (Margaix-Muñoz M, Bagán J, Poveda-Roda
R. Ewing sarcoma of the oral cavity. A review. J Clin Exp Dent. 2017 Feb 1;9(2):e294-e301. doi: 10.4317/jced.53575.
PMID: 28210452; PMCID: PMC5303334.)

• There is considerable clinical and histologic overlap between this tumor and the
PNET.

• Ewing's sarcoma arises within the bone, but can also occur within the soft tissue
(extraosseous Ewing's sarcoma) and PNET arises within soft tissues.
• Age: < 30 years, usually intraosseous

• Histopathologic features:
Uniform round cells
Individual cells have round to ovoid nucleus approx 10-15 µm
dia.,
Distinct nuclear membrane, fine powdery chromatin, 1-2 small
nucleoli
Cytoplasm ill defined, scanty, pale staining
No rosettes
Abundant to moderate glycogen
(Histological examination) HES  600 small-round-blue-cell
arrow head tumor with highly cellular areas. Insert (gross
examination) showed a pseudoencapsulated fleshy tumor
mass.
 Immunohistochemistry
• CD99 +ve
• FLI-1 +ve
• Less expression of neural markers

• Special Stains
PAS with diastase (glycogen present in 75% of cases)
 Cytogenetics
• Translocation, t(11;22) (q24;q12) i.e., fusion between the
5’end of the EWS gene from chromosome band 22q12 with
the 3’ portion of the 11q24 FLI1 gene is seen.

• This EWS/ETS fusion protein blocks the differentiation of

pluripotent marrow stromal cells.

• Rest 10-15% of the cases have t(21;22) (q22;q12) fusing EWS

to a closely related ETS gene.
 PNET
(Primitive Neuroectodermal Tumor)

• PNET is a small round cell malignancy of primitive,

neuroectodermal tissue or pluripotential, migratory neural crest
cells that arises from the soft tissue or bone, commonly
affecting older children and adults.

• The term, “PNET” includes MSRCTs of the thoracopulmonary

region (Askin's tumor), extraskeletal Ewing's sarcoma,
peripheral neuroblastoma, and peripheral neuroepithelioma.
• The tumor shows variable numbers of pseudorosettes;
fibrillary matrix and Homer Wright rosettes are seen at times,
and mitotic figures are rarely detected.
• Age: >40yrs; Usually peripheral

• Histopathologic features
Irregular cells
Small round cell containing darkly staining round to oval nucleus
Coarse chromatin granules
Prominent nucleoli
Cytoplasm is indistinct except in areas where cells are more mature and
elongated hair like extensions coalesce to form rossettes
Rosettes are similar to neuroblastoma and contain solid core of
neurofibrillary material (Homer wright rosette)
Rarely resemble retinoblastoma containing central lumen or vesicle
(flexener- winterstien rosette)
Scant glycogen
Ewing sarcoma. (A) Classical Ewing sarcoma. High-power view shows a monotonous population of
small round cells with fine chromatin, inconspicuous nucleoli, and cytoplasmic clearing due to
accumulation of glycogen. (B) Immunohistochemical stain for CD99 typically shows a diffuse, strong,
membranous staining pattern. (C) Geographic areas of necrosis and perivascular cuffing are
commonly seen. (D) Primitive neuroectodermal tumor (PNET) with area of confluent Homer Wright
rosettes, indicative of neural differentiation. 
HomereWright-type rosettes (arrow), a typical histological feature of primitive neuroectodermal tumors
 Hematoxylin and eosin staining of the tumor showing small round blue tumor cells with prominent nuclei and
nucleoli, scant cytoplasm, arranged in nests (rosettes) in the background of fibrous stroma

Dutta D, Shivaprasad KS, Das RN, Ghosh S, Chowdhury S. Primitive neuroectodermal tumor of adrenal: clinical presentation and
outcomes. J Cancer Res Ther. 2013 Oct-Dec;9(4):709-11. doi: 10.4103/0973-1482.126459. PMID: 24518722.
 • Immunohistochemistry:
CD 99 +ve
FLI-1 +ve
Increased expression of neural markers

• Cytogenetics:
Same as ewing sarcoma
 Hodgkin’s Lymphoma
• HL is a disorder arising primarily in lymph nodes in most cases (> 90%). Classic
HL (95%; nodular sclerosis, mixed-cellularity, lymphocyte-rich classic, and
lymphocyte-depletion types) has a bimodal age distribution, with an early peak
among young adults (aged 20 – 24 years) and a second, smaller peak among older
adults (aged 80 – 84 years).

• All types of HL are characterized by the presence of a small number of distinctive

large neoplastic cells, including binucleated or multinucleated cells (Reed-Sternberg
cells) and mononuclear variants (Hodgkin cells) that reside in a background of non-
neoplastic inflammatory and accessory cells and, sometimes, fibrosis.

• Recent studies using immunohistochemical and molecular genetic techniques have

shown that the origin of the neoplastic cells in nearly all cases of all types of HL is
the B lymphocyte.

• The distinction between HL and NHL can only be made by histopathologic

examination because clinical presentation and imaging studies fail to distinguish
these two groups of lymphomas.
Weber AL, Rahemtullah A, Ferry JA. Hodgkin and non-Hodgkin lymphoma of the head and neck: clinical, pathologic, and
imaging evaluation. Neuroimaging Clin N Am. 2003 Aug;13(3):371-92. doi: 10.1016/s1052-5149(03)00039-x. PMID: 14631680.
• Age: 15-34 years and older; >55years

• Histopathologic features
Reed-Sternberg cells
 • Immunohistochemistry:
CD30

• Cytogenetics
HLA-DP alleles
Hodgkin ’ s lymphoma histology showing classical Reed-Sternberg cells (see
boxes) with a mixed cellularity background. H&E stain.
 Diffuse large B cell
lymphoma
• Age: >50years

• Histopathologic features
Large irregular or lobated nuclei, size 4-5 times that of small
lymphocytes.

• Immunohistochemistry:
Positive for CD20, CD45 and monotypic Ig. Positive for CD20, CD
10, BCL 6

• Cytogenetics:
t(14;18)(q32;2) Trisomy gains of 3q, 18q21-q22 and loss of 6q21-
22.
The malignant lymphocytes here are very large with a moderately abundant cytoplasm, and the nuclei are round to
ovoid with prominent nucleoli and occasional mitoses. The diagnosis is diffuse large B cell lymphoma (also known
as immunoblastic lymphoma). Demonstration of CD19 and 20 antigens would classify it as B cell in origin.
 Small lymphocytic lymphoma
(SLL)
• Age: Older individuals

• Histopathologic features:
Proliferation of non-activated, mature looking small lymphocytes
selectively involving the interfollicular regions or B-zones of the node.
The para-immunoblasts and pro-lymphocytes are hallmark of SLL.

• Immunohistochemistry:
CD 20 +ve, weak monotypic surface Ig. Ki 67 index is low.

• Cytogenetics:
Deletions of 13q14.
 Follicular lymphoma
• Age: >50 years

• Histopathologic features:
Nodular growth of monotonous cells.
Three types:
1. Contains small cells (size of normal lymphocyte)
2. Has large cells (2 to 3 times the size of normal lymphocyte,
resembles mitotically active germinal centre cell)
3. Intermediate (contains both small and large lymphocytic cells).
 • Immunohistochemistry:
CD19, CD20, CD10, BCL-2 positive.

• Cytogenetics:
t(14;18)(q32;q2)
 Mantle cell lymphoma
• Age: Older individuals

• Histopathologic features:
Medium to large sized monomorphic round neoplastic cells, arranged
in diffuse or nodular pattern, hyalinised small blood vessels, and
scattered epithelioid cells.

• Immunohistochemistry:
Positive for CD5, CD20, CD43, BCL 1, negative for CD10, BCL 6
• Cytogenetics:
t(11;14)(q13;q32 ). Increased cyclin D1 expression.
 Burkitt’s lymphoma
• Burkitt's lymphoma (LB) is a form of malignant non-Hodgkin's lymphoma that
arises from the malignant course and proliferation of type B lymphoid cells.

• Burkitt lymphoma (BL) is a rare and aggressive malignant neoplasm frequently

involving the jawbones in children.

• The World Health Organization (WHO) classifies 3 variants of BL: endemic,

sporadic, and immunodeficiency-associated types.

• The endemic form frequently develops in African children and adolescents and
is almost invariably associated with Epstein-Barr virus (EBV) infection.
• The sporadic form has no geographic predilection and develops most
commonly in adults.
• The jawbones are much more commonly affected in the former variant.
• The immunodeficiency-associated variant is only rarely associated with
orofacial involvement.
 • Age: Occur in children

Three variants:
1. Endemic: refers to Burkitt’s occurring in African children. Epsten Barr
Virus (EBV) + in all most all cases.
2. Sporadic: Occurs in all geographic areas. EBV + in 15%- 30% of cases.
3. Immunodifficiency associated: Common in HIV+ patients. May show
plasmacytoid differentiation.

• Histopathological features:

Uniform or slightly pleomorphic medium sized cells, moderate amount of

cytoplasm,
Starry sky pattern due to admixed tingible body macrophages,
high mitotic rate and necrosis.
• In the classic form, neoplastic cells are monotonous
intermediate-sized cells with round nuclei and multiple
peripheral nucleoli surrounded by scant amounts of cytoplasm
and clear vacuoles.
• Mitotic figures are abundant; as are tingible body macrophages
that contain phagocytosed apoptotic debris creating the
“starry sky” pattern visible at low-power microscopy.

• Unlike classic BL, atypical BL exhibits more nuclear

pleomorphism and has fewer, more prominent nucleoli,
whereas BL with plasmacytoid differentiation contains cells
with an eccentric nucleus, often with a single nucleolus.
A, An incisional biopsy of the oral lesion contained a diffuse proliferation of monotonous,
intermediate- to large-sized lymphocytes with round to irregular nuclei, fine chromatin, multiple small
peripheral nucleoli and scant cytoplasm (hematoxylin and eosin [H&E], magnification 400). B, A
tandem bone marrow biopsy showed replacement of normal hematopoiesis by a diffuse monotonous
infiltrate of neoplastic lymphocytes identical to those seen in the gingival biopsy (H&E,
magnification 400).
Diffusely arranged sheets of neoplastic cells with starry sky appearance
 • Immunohistochemistry:
Positive for CD 20, CD10, Monotypic Ig

• Cytogenetics:
80% with t(8;14) translocation, 20% t(2;8) or t(8;22)
Immunohistochemical studies demonstrated that the neoplastic cells were CD20 B cells (A) that expressed
germinal center markers BCL6 (B) and CD10 (C) and were negative for BCL2 (D), also consistent with
germinal center derivation (magnification 400).

Balasubramaniam R, Goradia A, Turner LN, Stoopler ET, Alawi F, Frank DM, Greenberg MS. Burkitt lymphoma of the oral
cavity: an atypical presentation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Feb;107(2):240-5. doi:
10.1016/j.tripleo.2008.09.008. PMID: 19138642.
 MALT lymphoma
• Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of
extranodal marginal zone B-cell lymphoma and is a distinct subtype of
non-Hodgkin's lymphoma.

• The most common site of MALT lymphomas is the stomach.

• Other sites where MALT lymphomas can occur include the orbit, lung,
salivary glands, thyroid, skin, intestine, and liver.

• Salivary gland and thyroid MALT lymphomas are associated with

autoimmune disorders such as Sjogren's syndrome and Hashimoto
disease, respectively.

• Primary MALT lymphomas can also occur in the oral cavity, although
their appearance in this location is rare.
 • Age: Any age group

• Observed in salivary glands, thyroid, stomach etc, originate from marginal

zone B cells, shows cellular heterogeneity with monocytoid B cells, small
lymphocytes, plasma cells, and occasionally large lymphocytes.

• Histopathological features:

Two variants:
1. Few cases show prominent follicular growth pattern resulting from
follicular colonization, centrocyte-like (CCL) cells representing minimal
Positive for CD20, and surface Ig D. Negative for CD10, CD5.
2. Few cases show marginal zone distribution pattern of CCL cells,
presence of plasma cells.
 Low-power magnification (×50) show some colonized lymphoid follicles with mantle
zone in the primary MALT lymphoma (A). High-power magnification (×630) show
centrocyte-like cells, monocytoid B-cells, and neoplastic cells which have Dutcher body
in the primary MALT lymphoma (B).
 • Immunohistochemistry:
Positive for CD20, and surface Ig D. Negative for CD10, CD5

• Cytogenetics:
Trisomy 3, t(11;18) (q21;q21),27-32 t(1;14) (p22;q32),33 and
t(14;18) (q32;q21). 34.49
 NK/T cell lymphoma
• Age: >50 years

• Histopathological features:
Tissue densely populated by abnormal lymphocytes (small,
intermediate and large), areas of necrosis and angiocentric and
angiodestructive growth pattern.
• Immunohistochemistry:
CD56 +ve and CD2 +ve.

Absence of surface CD3 but presence of cytoplasmic CD3.

• Cytogenetics:
Lack of TCR genes rearrangements.
 Plasmablastic lymphoma
• Plasmablastic lymphoma (PBL) is a rare AIDS associated non-Hodgkin's
lymphoma (NHL), with predilection for the mucosa of oral cavity.
• It usually has a plasmablastic morphology, expressing plasma cell-associated
antigens with weak or no expression of B-cell associated markers.
• The tumor cells also show monoclonal rearrangement of the immunoglobulin
heavy chain gene (IgH) and/or clonal restriction of Ig light chain (IgL) gene
expression in most of the cases.
• An etiological role for EBV seems likely but the association with HHV8 is
questionable. 

• Histopathological features:
Found in HIV infected patients, diffuse infiltration of large neoplastic cells in the
oral submucosa with eccentrically placed nuclei and paranuclear halo.

• Immunohistochemistry:
CD 4-ve, and CD2-ve. VS38c + ve and CD79a
• Differential diagnosis for oral PBL includes poorly
differentiated carcinoma, amelanotic melanoma and other
types of lymhoproliferative diseases.
• Distinguishing these malignancies from oral PBL is crucial for
directing appropriate treatment.
• Poorly differentiated carcinoma can be differentiated from oral
PBL based on its consistent immunoreactivity for cytokeratins
and/or epithelial membrane antigen.
• Amelanotic melanoma can be ruled out by using specific
antigenic markers such as S-100 protein, HMB45 and Melan A
(MART-1).
 Tumor cells expressing strong positivity for (B)
Poorly differentiated, non-cohesive large lymphocytes
CD79a.original magnification X 40).
with sparse, darkly staining cytoplasm and
pleomorphic, basophilic nucleoli (hematoxylin–eosin,
original magnification X 40).

Sarode SC, Zarkar GA, Desai RS, Sabane VS, Kulkarni MA. Plasmablastic lymphoma of the oral cavity in an HIV-positive patient: a
case report and review of literature. Int J Oral Maxillofac Surg. 2009 Sep;38(9):993-9. doi: 10.1016/j.ijom.2009.03.720. Epub 2009
May 13. PMID: 19443181.
 Plasma cell neoplasias
• Age: 60-65years

• Histopathological features:
Three types: Multiple myeloma (multiple bones involved), solitary bone
plasmacytoma, and extramedullary plasmacytoma.
Shows proliferation of mature and immature plasma cell (eccentrically placed
nuclei with cartwheel appearance), bone marrow plasmacytosis, osteolytic lesions,
• M-protein in serum, and Bence-Jones protein in urine.

• Multiple myeloma (MM) is a hematologic neoplasm characterized by a

monoclonal plasma cell proliferation that usually presents the following
clinical features: hypercalcemia, renal failure, anemia and bone lesions
(CRAB). Some oral features may be observed in patients presenting MM, such
as swelling, pain, gingival bleeding, paresthesia and osteolytic lesions.
• In a study by Feitosa et al. a high frequency of oral manifestations
associated with the disease was observed in the soft (54.7%) and hard
(78.5%) tissues.
• Jawbone lesions in MM are commonly mentioned and have been
reported as one of the first detected signs of the disease.
•  Similarly to the results of this study, plasmacytoma lesions have been
described more often than the typical pattern of “punched out” lesions.
•  Plasmacytoma lesions have been characterized as large and irregular
radiolucent lesions, with poorly defined margins. 
• “Punched out” lesions are commonly visualized as multiple and
rounded radiolucencies with no corticalized well-defined margins.
•  The jawbone lesions are not pathognomonic of MM.
• Differential diagnosis with other maxillary pathological conditions,
such as chronic osteomyelitis, osteonecrosis, osteoradionecrosis,
ameloblastoma, osteosarcoma, Paget's disease and other conditions,
should be considered in the evaluation of the jaw images.
• Immunohistochemistry:
Monoclonal immune-globulins i.e., Ig G, lambda, Ig kappa

• Cytogenetics:
t(8;14), t(11;14) or t(14;18)
Histopathology showing sheets of plasma cells with several atypical forms
 Olfactory Neuroblastoma
• Age: adults and occur over wide age range (mean: 53 years)

Originate from basal cells of olfactory epithelium which express neural cell adhesion
molecule and the mammalian homologue of Drosophila-achaete-scute (MASH) gene.

• Histopathological features:

Lesion is compartmentalized into lobules by slender vascular fibrous septa.

The lobules contain cells with almost nonexistent cytoplasm, round nuclei with
sharply defined chromatin and plexiform intercellular fibrils True rosettes/ Flexner-
Wintersteiner rosettes (consists of spaces lined by columnar cells with nuclei oriented
radially around the space) and pseudorosettes / Homer Wright rosettes are seen.
Cytoplasm shows secretory granules similar to catecholamine granules.
Pattern I: A tumor with sheets of small, round cell separated by
connective tissues septa; pseudorosettes or Homer Wright rosettes are
seen.

Pattern II: Consists of cells with round to oval nuclei with clear
nuclear membranes, scanty cytoplasm and indistinct cell borders. True
rosettes or FlexnerWintersteiner are seen.

Pattern III: Pattern similar to neuroblastoma with production of

neuropil, a wispy, light pink, fibrillar material produced by
undifferentiated neuroblasts.
Rosettes are seen with abundant haemorrhage, fibrosis and
hemosiderin deposition. Clusters of lymphocytes and islands of
dystrophic calcification are seen.
 • Immunohistochemistry:
positive for neuron specific enolase and neural filament protein.
S-100 and vimentin are positive in sustentacular cells.

• Cytogenetics:
express HASH, the human homologue of the MASH gene.
 Rhabdomyosarcoma
• Rhabdomyosarcoma (RMS), the most common soft tissue
sarcoma of childhood, is a mesenchymal-derived malignant
neoplasm.
• Among head and neck RMSs, two-thirds occur in children
(ages 0–19) and one-third occur in adults (age > 19).
• The most frequently involved site of head and neck RMS is the
orbit, accounting for 25 % of cases.
• Alveolar RMS is the second most common subtype, followed
by the pleomorphic variant, accounting for the bulk of the
remaining cases.

McInturff M, Adamson A, Donaldson C, Nelson BL. Embryonal Rhabdomyosarcoma of the Oral Cavity. Head
Neck Pathol. 2017 Sep;11(3):385-388. doi: 10.1007/s12105-016-0761-2. Epub 2016 Oct 14. PMID:
27743320; PMCID: PMC5550385.
 • Age: children, Thought to arise from skeletal muscle progenitors

• Histopathological features:

Embryonal rhabdomyosarcoma (ERMS): tumor cells vary from being small

undifferentiated round or spindle shaped cells to number of differentiated cells
with eosinophilic cytoplasm characteristic of rhabomyoblasts floating in a sea
of primitive mucous ground substance.

Cross-striations are discernible in 50–60% of cases alveolar

rhabdomyosarcoma (ARMS): tumors are composed of round cells with scanty
cytoplasm and nuclei that is uniform in size and shape with coarse chromatin.
Sometimes it consists of one or two prominent nuclear folds.

Nuclear necrosis and pyknosis with high mitotic activity is usually observed.
• Immunohistochemistry:
Myogenin, Myo D

• Special Stains:
• PAS with or without diastase: For intracellular glycogen
• Colloidal iron and alcian blue: For extracellular mucinous material
• Masson's trichrome, phosphotungstic acid hematoxylin.

• Cytogenetics:
Alveolar RMS shows t(2;13)(q35;q14) translocation. The genes involved are
PAX3 (paired box gene) on chromosome 2 and FKHR (Forkhead domain) on
chromosome13. Embryonal RMS are usually hyper-diploid and do not show
t(2;13). There is loss of heterozygosity for 11p15 region. The neoplasms have
extra copies of chromosome 2,8,9,11,12 and 13.8
Low power hematoxylin and eosin image shows the tumor consists primarily
of small round, polygonal tumor cells. Cells have variable amounts of
eosinophilic cytoplasm and hyperchromatic nuclei
A high power hematoxylin and eosin demonstrates many small round cells but also highlights the elongated
tumor cells. These cells are often times referred to as strap cells. Note the pleomorphism and numerous mitotic
figures
MyoD1 shows nuclear reactivity
 Small cell ostosarcoma
• Age: Peak in 4th decade of life

• Histopathological features:
The cells grow in solid nests or in lobules with densely cellular
central areas and decreasing cellularity with deposition of more
extracellular material (osteoid) at the periphery.

• Immunohistochemistry:
Osteocalcin, Osteonectin

• Cytogenetics:
CBFA 1 gene positive.
 Mesenchymal chondrosarcoma
• Age: peak in second decade

• Histopathological features:
Primitive small oval and round cells, hemangiopericytoma
vascular pattern, islands of cartilage or hyalinization.

• Immunohistochemistry:
CD 99, S-100 positive and collagen II positive.

• Cytogenetics:
Has unique del (13; 21) (q10; q10) translocation.
 Merkel cell carcinoma
• Age: Adults

• Histopathological features:
Tumor originates either from neural crest or stem cell and consists
of small blue round cells.

• Immunohistochemistry:
Positive for CK 20 (paranuclear dot), NSE, NF, EMA,
chromogranin, and synaptophysin.
 Paraganglioma
• Age: Middle age

• Histopathological features:
Round or polygonal epitheloid cells organized into nests or
ZELLBLLEN
Zellbllen are larger and irregular in shape
Nests consists of CHIEF cells which demonstrate centrally
located, vesicular nuclei and somewhat granular eosinophilic
cytoplasm
Tumor is vascular
Surrounded by thin fibrous capsule .
 Langerhans cell histiocytosis/ histiocytosis X

• Age: 10- 20 years

• Histopathological features:
Diffuse infiltration of large mononuclear cells that resemble
histiocytes
Cells have cytoplasmic borders and rounded/ indented vesicular
nuclei
Varying number of eosinophils are interspersed among histiocyte
like cells
Plasma cells, lymphocytes and multinucleate giant cells are often
seen
Ultrastructuraly, langerhans cells contain rod shaped cytoplasmic
structures known as Birbeck granules
 • Immunohistochemistry:
S100, CD1a

• Cytogenetics:
HLA-DR allele
Photomicrograph (original magnification, ×400; hematoxylin-eosin stain) shows a proliferation of
Langerhans cells (straight arrows), which are characterized by a moderate amount of eosinophilic
cytoplasm, elongated kidney-shaped nuclei, and a nuclear groove (curved arrows). The Langerhans cells are
associated with macrophages, lymphocytes, and numerous eosinophils (arrowheads).
Electron photomicrograph (original magnification, ×46,000) shows Birbeck bodies within the
cytoplasm of a Langerhans cell. Note the zipperlike central core and the bulbous structure at one
end of each Birbeck body, features that cause it to resemble a tennis racket (arrows).
 Granulocytic Sarcoma/ Myeloid
Sarcoma (Chloroma)
• Histopathological features:
Characteristic microscopic growth pattern of myeloid cells is
either a diffuse or an Indian file pattern
It is subclassified according to the most abundant cell type into
granulocytic, monoblastic or myelomonocytic and according to
cell maturation into immature, mature and blastic types.
Blastic type is composed primarily of myeloblasts with little
evidence of maturation.
The immature type is an intermediate grade and consists of
myeloblasts, promyelocytes and eosinophilic myelocytes.
The differentiated or mature type is composed of promyelocytes
and more mature cells with abundance of eosinophils
 • Immunohistochemistry:
CD4. CD13, CD33, CD117 and MPO
KI-67/MIBI is usually high, ranging from 50% to 95%

• Cytogenetics:
NPM
 Immunohistochemistry of Round Cell
Tumors
• Markers:

1. CD 99
• CD 99 is a transmembrane glycoprotein of 30–32 KDa
• It plays a role in cellular adhesion and regulation of cellular proliferation
• Normal tissue that commonly displays strong expression of CD99 include:
• Cortical thymocytes
• Sertoli cells
• Endothelium
• Pancreatic islets
• Ependyma
• Epithelium (urothelium, squamous epithelium, columnar epithelium)
• It is specific for:
• Ewing's sarcoma – 90%
• Lymphoblastic lymphoma – 90%
• Synovial sarcoma – >75%
• Mesenchymal chondrosarcoma – 50%
• Osteosarcoma and desmoplastic round cell tumor – Rare
• Neuroblastoma – Never reported (-).
• NB 84
• It is sensitive marker for neuroblastoma (75%), Ewing's sarcoma (16%–25%)
• Also positive for osteosarcoma, desmoplastic round cell tumor.

• S-100
• It is a marker for benign and malignant nerve sheath tumors
• Composed of two subunits α and β that combine to form 3 isotypes: α-α isotype found in the
myocardium, skeletal muscle and neurons, α-β isotype found in chondrocytes, glia and skin
adnexae, β-β isotype found in Langerhans and Schwann cells.

• Desmin
• It is the intermediate filament protein associated with both smooth and skeletal muscle
differentiation
• Rarely expressed by myofibroblasts and their corresponding tumors
• In skeletal muscles desmin is localized to Z-zone between myofibrils when it serves as
binding material for contractile apparatus. In smooth muscles, it is associated with
cytoplasmic dense bodies
• Desmin can also be expressed by nonmuscle cells including fibroblastic reticulum cells of
lymph nodes, submesothelial fibroblast, and endometrial stromal cells
• Expressed in PNET, desmoplastic round cell tumors, neuroblastoma, mesothelial cells .
• Cytokeratins
• Used for distinguishing epithelial from nonepithelial tumors
(lymphomas, sarcomas, melanomas)
• Expressed in: Carcinoma, epithelial sarcoma, leiomyosarcoma,
mesothelioma
• Also expressed by round cell tumors such as Ewing's
sarcoma/PNET, desmoplastic round cell tumor.

• PAX 5
• PAX 5 is a member of the paired box transcription factors involved
in the development and is expressed in hematopoietic malignancies
of B-cell lineage
• Expressed in cases of neuroendocrine carcinomas, urothelial
tumors, Merkel cell carcinoma, glioblastoma, and neuroblastoma
• Also positive for B-cell lymphoblastic lymphomas, ARMS
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