Soft tissue – Fibrosarcoma

What are the defining characteristics of fibrosarcoma cells?

Fibrosarcoma cells resemble normal fibroblasts.

Why has there been subjectivity in classifying spindle cell tumors as fibrosarcoma?

Classification criteria have evolved over time, leading to varying incidences and behaviors of
fibrosarcoma.

How has the incidence of adult-type fibrosarcoma changed over the years?

The incidence has declined, with recent estimates suggesting it accounts for less than 1% of adult soft
tissue sarcomas.

What contributed to the decline in fibrosarcoma diagnosis?

Pathologists categorizing tumors as "malignant fibrous histiocytoma" or "undifferentiated pleomorphic

sarcoma," and the recognition of distinct tumor types using advanced techniques.

What role does immunohistochemistry (IHC) play in diagnosing fibrosarcoma?

IHC helps exclude other diagnoses, such as synovial sarcoma and malignant peripheral nerve sheath
tumor.

Can adult-type fibrosarcoma exhibit myofibroblastic features?

Yes, it can have myofibroblastic components, but this does not rule out the diagnosis of fibrosarcoma.

How are high-grade, collagen-forming spindle cell tumors typically classified?

They are often classified as undifferentiated pleomorphic sarcomas.

What are some variants or subsets of adult-type fibrosarcoma?

Variants include myxoid fibrosarcoma, low-grade fibromyxoid sarcoma, sclerosing epithelioid

fibrosarcoma, and myofibroblastic sarcoma.

Are these fibrosarcoma variants biologically distinct?

It's not entirely clear, but they have distinct histologic and sometimes molecular genetic features for
consistent identification.

What is myxoid fibrosarcoma, also known as myxofibrosarcoma?

It's a variant characterized by myxoid stroma within fibrosarcoma.

What distinguishes low-grade fibromyxoid sarcoma?

It has specific histologic features, including fibromyxoid stroma and a t(7;16) translocation.

What are the key features of sclerosing epithelioid fibrosarcoma?

It features epithelioid morphology and sclerosis within fibrosarcoma.

What is myofibroblastic sarcoma, and when did it gain recognition?

Myofibroblastic sarcoma predominantly comprises myofibroblasts and gained recognition over the
past 15 years.

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How has the diagnosis of adult-type fibrosarcoma changed over time?

It has become a diagnosis of exclusion, relying on the elimination of other sarcoma types through
advanced diagnostic techniques.

What grade of fibrosarcoma do most lesions diagnosed as adult-type fibrosarcoma belong to?

They typically fall into the low-grade end of the spectrum, ranging from grades 1 to 2.

What is the significance of actin isoforms in fibrosarcoma diagnosis?

The presence of various actin isoforms within fibrosarcoma does not rule out the diagnosis.

What are deep fibromatoses, and how are they distinct from fibrosarcoma?

Deep fibromatoses, also known as desmoid tumors, are a distinct group of tumors separate from
fibrosarcoma.

How have cytogenetic and molecular genetic techniques impacted the diagnosis of fibrosarcoma?

These techniques have improved the ability to recognize other sarcoma types, reducing
misclassifications as fibrosarcoma.

What is the current approach to diagnosing adult-type fibrosarcoma?

It involves excluding other sarcoma types using advanced diagnostic methods.

What has been the overall trend in the diagnosis and understanding of adult-type fibrosarcoma?

It has evolved from a common diagnosis to a rare one, with efforts to identify distinct variants and
subsets within this group of lesions.

What is the typical grade range for adult-type fibrosarcoma?

Adult-type fibrosarcoma primarily falls within grades 1 and 2 on the grading scale.

How do advanced diagnostic techniques like cytogenetics and molecular genetics aid in fibrosarcoma
diagnosis?

These techniques help identify specific genetic alterations and markers associated with fibrosarcoma,
aiding in accurate diagnosis.

What is the significance of the term "undifferentiated pleomorphic sarcoma" in the context of
fibrosarcoma diagnosis?

It is often used to classify high-grade, collagen-forming spindle cell tumors, which are considered
separate from fibrosarcoma.

What is the role of histologic criteria in distinguishing fibrosarcoma from other spindle cell tumors?

Histologic criteria help pathologists differentiate fibrosarcoma from similar tumors like synovial
sarcoma and malignant peripheral nerve sheath tumor.

Why is it challenging to diagnose spindle cell tumors when only a small biopsy specimen is available?

Limited tissue samples make it difficult to assess key histologic and genetic features needed for
accurate diagnosis.

How has the understanding of fibrosarcoma evolved over the past 50 years?

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It has transitioned from being a more common diagnosis to a rare one, with a focus on recognizing
distinct variants and subsets.

What are some key molecular genetic features associated with fibrosarcoma?

Specific chromosomal rearrangements and genetic markers can be associated with fibrosarcoma,
aiding in its identification.

Can fibrosarcoma have myofibroblastic components, and if so, does it affect the diagnosis?

Yes, fibrosarcoma can contain myofibroblastic components, but this does not preclude its diagnosis.

What is the relationship between deep fibromatoses (desmoid tumors) and fibrosarcoma?

Deep fibromatoses are distinct tumors separate from fibrosarcoma, with different characteristics and
behaviors.

How have advances in immunohistochemistry (IHC) improved the diagnosis of fibrosarcoma?

IHC plays a crucial role in excluding other sarcoma types, allowing for a more accurate diagnosis of
fibrosarcoma.

What are the typical clinical symptoms of adult-type fibrosarcoma?

Adult-type fibrosarcoma usually presents as a painless, slowly growing solitary mass, ranging from 3
to 8 cm in size.

When might adult-type fibrosarcoma become painful?

Pain is less common with fibrosarcoma but may occur more often with synovial sarcoma and
malignant peripheral nerve sheath tumor (MPNST).

What happens to the skin overlying adult-type fibrosarcoma?

Generally, the skin remains intact, but rapid growth or trauma may lead to skin ulceration, especially
in neglected cases.

How long can symptoms persist before diagnosis?

Symptoms can vary widely, lasting from a few weeks to as long as 20 years before diagnosis.

At what age is adult-type fibrosarcoma most commonly diagnosed?

Adult-type fibrosarcoma is most common in the third through fifth decades of life, with a median age of
around 50 years.

Which soft tissue sites are commonly affected by fibrosarcoma?

Deep soft tissues of the lower extremities, particularly the thigh and knee, are most commonly
affected. However, it can occur in virtually any anatomic site.

What structures within deep soft tissues does fibrosarcoma often originate from?

Fibrosarcoma tends to originate from intramuscular and intermuscular fibrous tissue, fascial
envelopes, aponeuroses, and tendons.

How can radiographic findings aid in diagnosing fibrosarcoma?

Radiographic findings may include soft tissue masses, occasional calcification and ossification, and,
in some cases, periosteal and cortical thickening when bone is encircled.

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Where do fibrosarcomas that arise from the subcutis tend to originate?

Subcutaneous fibrosarcomas are rare and typically arise in tissues damaged by radiation, heat, or
scarring.

In which cases do fibrosarcomas tend to form large fungating masses?

Fibrosarcomas may form large fungating masses in areas of ulceration, particularly when left
untreated or neglected.

What does an excised adult-type fibrosarcoma mass typically look like?

It is usually a solitary, soft to firm, gray-white to tan-yellow, rounded or lobulated mass measuring 3 to
8 cm in size.

How are small fibrosarcomas typically defined histologically?

Small fibrosarcomas are often well-circumscribed and may be partly or completely encapsulated.

What complications can arise from the frequent circumscription of small fibrosarcomas?

The circumscription of small fibrosarcomas may lead to misdiagnosis as a "benign tumor" and result
in inadequate surgical therapy.

What is the predominant histologic growth pattern in adult-type fibrosarcomas?

Adult-type fibrosarcomas typically exhibit a uniform fasciculated growth pattern of spindle-shaped

cells with interwoven collagen fibers.

How is histologic grading of adult-type fibrosarcomas determined?

Histologic grading is based on factors such as cellularity, differentiation, mitotic activity, and necrosis.

What characterizes low-grade fibrosarcomas histologically?

Low-grade fibrosarcomas have a uniform, orderly appearance of spindle cells associated with
abundant collagen, often in a herringbone pattern.

What distinguishes high-grade fibrosarcomas from low-grade ones?

High-grade fibrosarcomas feature closely packed, less well-oriented tumor cells with smaller,
pleomorphic nuclei, more mitotic figures, and areas of necrosis and hemorrhage.

When might tumors containing multinucleated giant cells or giant cells be better classified as?

Tumors with these features are often better classified as undifferentiated pleomorphic sarcomas
(UPS).

What challenges may arise in distinguishing fibrosarcoma from fibromatosis?

In some cases, both conditions may appear similar histologically, especially when evaluating small
biopsy samples.

In summary, what is the histologic classification of high-grade fibrosarcomas?

High-grade fibrosarcomas are best classified as undifferentiated pleomorphic sarcomas (UPS) due to
their distinct histologic features.

What lineage-specific markers are typically absent in fibrosarcoma?

Fibrosarcomas lack lineage-specific markers such as keratin or S-100 protein.

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How can fibrosarcoma be distinguished from monophasic fibrous synovial sarcoma
immunohistochemically?

Fibrosarcoma is negative for keratin, while monophasic fibrous synovial sarcoma typically expresses
at least one epithelial marker.

What distinguishes fibrosarcoma from spindle cell or desmoplastic malignant melanomas?

Negative immunostaining for S-100 protein and/or SOX10 helps distinguish fibrosarcoma from
malignant melanomas.

Is there a reliable immunostain for fibrosarcoma diagnosis?

Fibrosarcomas may show scattered cells expressing SMA or MSA, reflecting focal myofibroblastic
differentiation.

When is strong CD34 staining typically seen in fibrosarcomas?

Strong CD34 staining is typically observed in fibrosarcomas arising in dermatofibrosarcoma

protuberans (DFSP) or from a solitary fibrous tumor.

What is known about the cytogenetic and molecular genetic alterations in adult-type fibrosarcoma?

Little is known about these alterations, and there is no characteristic cytogenetic abnormality in this
tumor.

Have any specific cytogenetic abnormalities been reported in adult-type fibrosarcoma?

Some reports mention complex chromosomal rearrangements, including a nonrandom change

involving t(2;19) with 2q21-qter involvement.

Why is it often challenging to distinguish adult-type fibrosarcoma from other spindle cell tumors?

Fibrosarcoma diagnosis is typically one of exclusion, and multiple sections and ancillary studies are
often required for a correct diagnosis.

What are some benign conditions that can be mistaken for fibrosarcoma?

Benign conditions often confused with fibrosarcoma include nodular fasciitis, cellular benign fibrous
histiocytoma, and fibromatosis.

What malignant neoplasms are commonly considered in the differential diagnosis of fibrosarcoma?

Malignant neoplasms in the differential diagnosis include malignant peripheral nerve sheath tumor
(MPNST), undifferentiated pleomorphic sarcoma (UPS), and monophasic fibrous synovial sarcoma.

How does nodular fasciitis differ from fibrosarcoma histologically?

Nodular fasciitis is characterized by smaller size, a more irregular growth pattern, and cells arranged
in short bundles rather than long, sweeping fascicles seen in fibrosarcoma.

What distinguishes cellular benign fibrous histiocytoma from fibrosarcoma?

Cellular benign fibrous histiocytoma may resemble fibrosarcoma but often has less regular and
shorter fascicles. Benign areas of fibrous histiocytoma can also aid in differentiation.

In which tissue layers is deep fibromatosis typically found, and how does it differ from fibrosarcoma?

Deep fibromatosis is less cellular, contains more collagen, and is typically found in the dermis or
subcutis, unlike fibrosarcoma, which occurs in deep soft tissue structures.

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What clinical and histologic characteristics differentiate undifferentiated pleomorphic sarcoma (UPS)
from fibrosarcoma?

UPS primarily affects elderly individuals, has a storiform to haphazard growth pattern, and often
contains multinucleated bizarre giant cells, siderophages, and xanthoma cells.

How can malignant peripheral nerve sheath tumor (MPNST) be distinguished from fibrosarcoma?

MPNST must display some evidence of nerve sheath differentiation. MPNST cells may show wavy or
buckled appearances, and perivascular cuffing, distinct whorls, and myxoid areas are often present.

What markers are typically expressed in synovial sarcoma but not in fibrosarcoma?

Synovial sarcoma typically expresses epithelial markers, and TLE1 is a reliable marker for synovial
sarcoma. Detection of t(X;18) by FISH or RT-PCR is also specific for synovial sarcoma.

How does clear cell sarcoma differ from fibrosarcoma?

Clear cell sarcoma has clear cytoplasm and melanocytic differentiation, while fibrosarcoma lacks
these features.

What features differentiate epithelioid sarcoma from fibrosarcoma?

Epithelioid sarcoma consists of epithelioid cells with vesicular nuclei and abundant eosinophilic
cytoplasm, unlike fibrosarcoma.

What is the significance of nuclear β-catenin immunoreactivity in deep fibromatosis?

Deep fibromatosis typically shows aberrant nuclear β-catenin immunoreactivity, which is not seen in
fibrosarcoma.

In summary, what is the key factor in differentiating fibrosarcoma from other tumors?

Fibrosarcoma diagnosis often relies on careful exclusion and differentiation from other spindle cell
tumors through multiple examinations and ancillary studies.

How does spindle cell rhabdomyosarcoma differ from fibrosarcoma?

Spindle cell rhabdomyosarcoma contains cells with rhabdomyoblastic differentiation, while

fibrosarcoma lacks these features.

What distinguishes malignant melanoma with spindle cell features from fibrosarcoma?

Spindle cell melanomas typically express melanocytic markers such as S-100 protein and Melan-A,
which are absent in fibrosarcoma.

How can spindle cell carcinoma be differentiated from fibrosarcoma?

Spindle cell carcinoma usually exhibits cytokeratin positivity, which is not seen in fibrosarcoma.

What histologic features help distinguish desmoplastic leiomyosarcoma from fibrosarcoma?

Desmoplastic leiomyosarcoma often displays smooth muscle differentiation with fascicles of spindle
cells and may exhibit desmin or smooth muscle actin (SMA) immunoreactivity.

What markers may help differentiate sarcomatoid mesothelioma from fibrosarcoma?

Sarcomatoid mesothelioma may express markers such as calretinin, WT-1, and D2-40 (podoplanin),
which are not typically seen in fibrosarcoma.

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How does clear cell sarcoma of tendons and aponeuroses differ from fibrosarcoma?

Clear cell sarcoma contains clear cytoplasm, melanocytic differentiation, and often displays
translocation involving EWSR1-ATF1, distinguishing it from fibrosarcoma.

What is the role of genetic markers such as t(X;18) in the diagnosis of fibrosarcoma?

The presence of t(X;18) detected by FISH or RT-PCR is specific for synovial sarcoma and not
observed in fibrosarcoma.

How does malignant mesenchymoma differ from fibrosarcoma?

Malignant mesenchymoma is a biphasic tumor composed of both mesenchymal and other tissue
types, whereas fibrosarcoma is typically monophasic with spindle cell morphology.

What differentiates malignant peripheral nerve sheath tumor (MPNST) from fibrosarcoma?

MPNST must show evidence of nerve sheath differentiation, with characteristic features such as wavy
cells, perivascular cuffing, and whorls, which are not typical of fibrosarcoma.

What role does H3K27me3 loss play in the diagnosis of MPNST?

Loss of H3K27me3 is often observed in MPNST, which may help support the diagnosis when
combined with other features, but it is not specific to MPNST.

What is Low-Grade Fibromyxoid Sarcoma (LGFMS), and when was it first recognized?

LGFMS is a distinct variant of fibrosarcoma first recognized in 1987.

How does LGFMS typically present clinically?

LGFMS often presents as a slowly growing, painless deep soft tissue mass, most commonly in young
to middle-aged adults.

In which anatomical locations does LGFMS most frequently occur?

LGFMS most commonly arises in the deep soft tissues of the lower extremities, especially the thigh,
but it can occur in various anatomical sites.

What distinctive histological feature characterizes hyalinizing spindle cell tumor with giant rosettes?

Hyalinizing spindle cell tumor with giant rosettes is an LGFMS variant characterized by collagen
rosettes within the tumor.

What are the demographics of LGFMS patients in terms of age and gender?

LGFMS can affect individuals ranging from 3 years to 78 years of age, with a male predominance.

What is the usual size range of LGFMS tumors?

LGFMS tumors typically range from 1 to 18 cm in diameter, with most falling in the 8 to 10 cm range.

What anatomical regions are commonly affected by LGFMS?

LGFMS often arises in the lower extremities, chest wall/axilla, shoulder region, inguinal region,
buttock, neck, and various other anatomical sites.

What is the typical growth pattern of LGFMS?

LGFMS exhibits a slow, infiltrative growth pattern within the deep soft tissues.

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Which cytogenetic and molecular findings are associated with LGFMS?

LGFMS is characterized by a specific chromosomal translocation involving t(7;16)(q32-34;p11),

resulting in the fusion of FUS and CREB3L2 genes.

What is the metastatic potential of LGFMS?

LGFMS has a significant metastatic potential, often presenting with late-stage metastases despite its
initially deceptive histological appearance.

Which site is the principal metastatic location for fibrosarcoma, and when are most metastases
observed?

The lung is the primary metastatic site, with most metastases appearing within the first 2 years after
diagnosis.

How often does lymph node metastasis occur in fibrosarcoma?

Lymph node metastasis is rare in fibrosarcoma, and regional lymph node excision is typically not
required in the initial treatment.

What role has trauma been suggested to play in the development of fibrosarcoma?

Trauma has been proposed as a potential causative factor in fibrosarcoma development, with cases
arising at sites of prior injury or scar tissue.

Besides trauma, what other factors have been associated with fibrosarcoma development?

Fibrosarcoma has been reported to develop following radiation therapy, placement of prosthetic
vascular grafts, and at sites of burn scars.

How has the diagnosis and classification of fibrosarcoma evolved over the years?

Fibrosarcoma diagnosis has become more specific, with stricter diagnostic criteria and the use of
immunohistochemistry and molecular techniques, resulting in a decrease in its diagnosed cases.

What percentage of cases initially diagnosed as fibrosarcoma met modern diagnostic criteria in a
recent Mayo Clinic study?

In a recent study, only 16% of cases initially diagnosed as fibrosarcoma met modern diagnostic
criteria.

What are some specific variants or entities that were often misclassified as fibrosarcoma in earlier
studies?

Misclassified entities included undifferentiated pleomorphic sarcoma, monophasic fibrous synovial

sarcoma, and various benign or malignant fibrous or myxoid neoplasms.

How do LGFMS and myxofibrosarcoma differ histologically?

LGFMS is characterized by a fascicular herringbone growth pattern and collagen rosettes, while
myxofibrosarcoma features a myxoid stroma and a more scattered spindle cell arrangement.

What immunohistochemical markers are typically expressed by LGFMS?

LGFMS cells often express vimentin or focal SMA (smooth muscle actin) on immunohistochemistry.

What genetic abnormality is associated with LGFMS?

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LGFMS is characterized by the specific chromosomal translocation t(7;16)(q32-34;p11), resulting in
the FUS-CREB3L2 fusion gene.