Soft tissue sarcoma Flashcards
Myxoinflammatory fibroblastic sarcoma
Solitary painless masses, typically of the distal extremities. Usually affects the acral dorsal extremities, particularly the hands. The hand, finger, and wrist account for about 60% of cases, and the foot and ankle for about 20%.
Histologically, infiltrative and multinodular, often centred in the subcutaneous tissue. Dense inflammation merging with stroma varying from myxoid to hyalinized and containing sheets and small foci of epithelioid and spindled cells. Some lesions contain foamy histiocytes, giant cells, and haemosiderin. The cellularity is quite variable between lesions. Amid the inflammatory background, scattered bizarre cells with large vesicular nuclei and macronucleoli reminiscent of Reed–Sternberg cells or virocytes are present.
There is some histologic overlap with hemosiderotic fibrolipomatous tumour, and hybrid tumors with der(10)t(1;10) have been reported. These tumors likely exist on a spectrum.
Molecularly, characterized by t(1;10). The breakpoints in chromosomes 1 and 10 cluster in TGFBR3 and in or near OGA (MGEA5), respectively, but do not result in an expressed fusion gene. Additionally, one third of MIFSs demonstrate BRAF-related fusions. Another common genetic event in both MIFS and HFLT is the presence of a 3p11.1-p12.1 amplicon, including the VGLL3 gene.
Immunohistochemistry is not helpful.
Local recurrences are common and often repeated. Metastases are rare, occurring in < 1% of cases after multiple recurrences. Initial complete excision is the best predictor of a favourable outcome
So basically, histologic features and t(1;10) make the diagnosis.
Dermatofibrosarcoma protuberans
Superficial, locally aggressive fibroblastic neoplasm, having a cellular storiform appearance and carrying a COL1A1-PDGFB or related fusion.
Scalloping of fat is common.
Diffusely CD34+
Ordinary DFSP never metastasizes. High grade metastasises in 5% of cases. Fibrosarcomatous DFSP metastasizes in 10–15% of cases.
“Fibrosarcomatous DFSP”
Fibrosarcomatous DFSP / Fibrosarcomatous transformation of DFSP
Often arises within a conventional DFSP with a sharp demarkation.
Dense cellularity, herringbone pattern fascicles. Plumper cells with more mitoses. Still usually NOT pleomorphic.
CD34 expression may be lost in fibrosarcomatous DFSP, and KI67 will be elevated.
Infantile fibrosarcoma
ETV6::NTRK3 driven sarcoma usually arising in infants.
Rarely other rearrangements involving NTRK1, BRAF, and MET
As the use of “fibrosarcoma” suggests, this is a densely cellular spindle cell tumor with herringbone pattern.
IFS can display a broad morphological spectrum. Most commonly, it is a cellular neoplasm composed of monomorphic spindled to ovoid cells with scant cytoplasm and slightly angulated nuclei. The cells may be arranged in randomly oriented compact sheets or in herringbone fascicles. The background stroma can range from collagenous to myxoid. A prominent haemangiopericytoma-like vascular pattern is often present (shown). Tumours with decreased cellularity and prominent collagen resembling fibromatosis or myofibromatosis can also be seen.
The most common sites of involvement are the superficial and deep soft tissues of the extremities, followed by the trunk and the head and neck. Analogous tumours in the kidney are designated cellular congenital mesoblastic nephroma.
The immunohistochemical profile is nonspecific, with variable expression of SMA, CD34, S100, and desmin
Sclerosing epithelioid sarcoma
An EWSR-family rearranged tumor, most commonly EWSR1-CREB3L1.
Rare malignant fibroblastic neoplasm characterized by epithelioid fibroblasts arranged in cords and nests and embedded in a dense sclerotic hyalinized stroma. A subset of sclerosing epithelioid fibrosarcomas are related morphologically and molecularly to low-grade fibromyxoid sarcoma.
The margins of sclerosing epithelioid fibrosarcoma are typically infiltrative into muscle, fascia, or periosteum. A characteristic feature is a prominent hyalinized sclerotic collagenous stroma, within which relatively bland and monomorphic epithelioid cells are arranged in cords, nests, or occasionally sheets. Some tumours contain more cellular fascicular areas. Pseudoalveolar or acinar growth patterns are occasionally seen. Hypocellular areas with myxoid or fibrous stroma are common. The tumour cells usually have clear cytoplasm and inconspicuous nucleoli.
Low-grade fibromyxoid sarcoma
An EWSR-family rearranged tumor, most commonly EWSR1-CREB3L1.
The most common sites of involvement are the proximal extremities and trunk, usually subfascial in depth. Notoriously infiltrative and horrible disease, despite its strikingly low-grade cytology.
Malignant fibroblastic neoplasm characterized by alternating collagenous and myxoid areas, deceptively bland spindle cells with a whorling growth pattern, and arcades of small blood vessels. An abrupt transition between these two areas is typical. The tumour cells are bland, spindled, and sometimes plump, and they grow in short fascicles or in a whorling pattern. Mitotic activity is generally inconspicuous. Arcades of small vessels and arteriole-sized vessels with perivascular sclerosis are seen. Occasionally, the vessels have a haemangiopericytoma-like pattern. Approximately 30% of cases contain collagen rosettes – a central core of hyalinized collagen surrounded by a cuff of epithelioid tumour cells.
Presentation is typically with a painless mass. In many cases, the mass has reportedly been present for > 5 years.
Molecular: The cytogenetic hallmark of low-grade fibromyxoid sarcoma is the t(7;16)(q33;p11), which is present, often as the sole change, in two thirds of cases.
IHC: MUC4 is an extremely helpful IHC for this tumor. If negative, this does not rule it out though - negative cases have been reported. Proceed to cytogenetics/FISH.
This tumor is probably on a spectrum with sclerosing epithelioid sarcoma.
Low-grade myofibroblastic sarcoma
Rarely metastasizing mesenchymal neoplasm, often having fibromatosis-like features, which tends to arise in the head and neck region.
Histologically, characterized by a diffusely infiltrative growth pattern, and (in deeply located neoplasms) tumour cells often grow between individual skeletal muscle fibres. Most cases are composed of spindle-shaped tumour cells arranged in cellular fascicles or show a storiform growth pattern. Neoplastic cells have ill-defined palely eosinophilic cytoplasm and fusiform nuclei that are either elongated and wavy with evenly distributed chromatin or plumper, more rounded, and vesicular with small nucleoli.
Rarely, hypocellular neoplasms with a more prominent collagenous (sometimes hyalinized) stroma have been described. Importantly, neoplastic cells show, at least focally, moderate nuclear atypia with enlarged, hyperchromatic, and irregular nuclei and slightly increased proliferative activity. These neoplasms may contain numerous thin-walled capillaries. The tumours may progress to morphologically higher-grade myofibroblastic sarcomas.
This is what is on the ddx for myofibroblastoma! So inspect carefully and make sure your myofibroblastomas have nice well-rounded borders and are not cytologically atypical.
IHC: Variable SMA and desmin. Some have nuclear beta catenin.
Molecular: Unknown
Ectomesenchymoma
A malignant, multiphenotypic sarcoma consisting of both mesenchymal and neuroectodermal lines of differentiation. Biphasic neoplasm composed of areas resembling rhabdomyosarcoma intermixed with variable neuronal/neuroblastic components.
Pseudoendocrine sarcoma
Soft tissue sarcoma of uncertain lineage with sheets, nests, and trabeculae of epithelioid mesenchymal cells with rounded nuclei and speckled chromatin. Very reminiscent of a neuroendocrine tumor. . . but it’s not. Hence, “pseudoendocrine” sarcoma.
Have a propensity for the paraspinal regions of older adults. Have potential for local recurrence and distant metastasis.
Molecular: CTNNB1 exon 3 mutations.
Epithelioid sarcoma, proximal-type
aka, large cell-type
Very bad diagnosis. This is a highly malignant sarcoma that, unlike most sarcomas, regularly metastasizes to lymph nodes. The proximal-type subtype tends to arise in deep soft tissue, and it most often affects truncal (pelviperineal, genital, and inguinal) tissue, buttock, or hip.
Characterized by multinodular and sheet-like growth of large and sometimes pleomorphic epithelioid (carcinoma-like) cells with enlarged vesicular nuclei and prominent nucleoli. Spotty foci of tumour necrosis are frequently encountered, but this feature does not generally result in a pseudogranulomatous pattern typical of classic ES. Cells with rhabdoid features occur in both forms, but they are more frequently observed in the proximal-type subtype, in which differentiation from extrarenal rhabdoid tumour becomes challenging when the rhabdoid cell is the predominant cell type.
IHC/Molecular: Loss of SMARCB1/INI1. Keratin positive, EMA positive. CD34 positive in 50% of cases. ERG expression in 50% of cases.
Proximal-type with rhabdoid cells has a wrose prognosis than distal-type.
Epithelioid sarcoma, distal type
aka classical (non-large cell) type
Very bad diagnosis. This is a highly malignant sarcoma that, unlike most sarcomas, regularly metastasizes to lymph nodes. The distal type consists of cellular nodules of epithelioid and spindled tumour cells with central degeneration and/or necrosis – a growth pattern that imparts a vaguely granulomatous appearance to the process. Fusion of necrotizing nodules results in a serpiginous mass with central geographical necrosis. Deep-situated lesions spread along the fascia as undulating bands of cells punctuated by foci of necrosis.
Tumour nodules are composed of large ovoid or polygonal epithelioid cells and plump spindle-shaped cells with deeply eosinophilic cytoplasm and mildly atypical nuclei possessing vesicular chromatin and small nucleoli. The epithelioid cells, which are generally concentrated towards the centre of the nodule, gradually transition with the spindled element. Epithelioid cells may exhibit cytoplasmic vacuoles, mimicking a vascular tumour. Some cases have predominantly spindled morphology. Mitotic activity is usually low. Dystrophic calcification and metaplastic bone formation are detected in 20% of cases.
IHC/Molecular: Loss of SMARCB1/INI1. Keratin positive, EMA positive. CD34 positive in 50% of cases. ERG expression in 50% of cases.
Extrarenal rhabdoid tumor
This rare tumour seems to arise most often in deep, axial locations such as the neck, paraspinal region, perineal region, abdominal cavity or retroperitoneum, and pelvic cavity. Largely confined to infants and children, demographically. The liver appears to be the single most common visceral location (70% of cases).
Consists of characteristic rounded or polygonal neoplastic cells with glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies, eccentric nuclei, and macronucleoli. Morphologically and genetically identical tumours also arise in the kidney and brain.
The tumour is characterized by rhabdoid cells with large vesicular rounded to bean-shaped nuclei, prominent nucleoli, and abundant cytoplasm, arranged in sheets or in a solid trabecular pattern. Many tumour cells have juxtanuclear eosinophilic, PAS-positive, diastase-resistant hyaline inclusions or globules. At the periphery, tumour cells infiltrate surrounding tissue. Nuclear pleomorphism is not evident, whereas mitotic figures are frequently observed. The tumour often shows loss of cellular cohesion. Some cases demonstrate predominant proliferation of undifferentiated small round cells, with only a small number of typical rhabdoid cells.
Familial cases are typically associated with germline mutations in SMARCB1/INI1.
IHC: Loss of SMARCB1/INI1. Expression of keratins.
Alveolar soft part sarcoma
Commonly involves deep soft tissues of the extremities (61%; predominantly the lower extremity [51%]), trunk (20%), internal organs (8%), and head and neck (9%). Primaries in the head and neck region, particularly in the orbit and tongue, are seen in children.
The ASPSCR1-TFE3 fusion protein localizes to the nucleus, where it functions as an aberrant transcription factor, causing c-Met overexpression and activation of c-Met signalling, rendering ASPS cells sensitive to clinical c-Met inhibition (crizotinib).
Molecular: t(X;17), which results in ASPSCR1-TFE3 gene fusion.
