General benign soft tissue tumors Flashcards
Fetal rhabdomyoma
Most arise in the head and neck (e.g. in the parapharyngeal space, salivary glands, larynx, mouth, and soft tissue)
May be associated with basal cell naevus syndrome, caused by loss-of-function mutations in the tumour suppressor gene PTCH1 , or Birt–Hogg–Dubé syndrome, caused by FLCN mutation.
Fetal rhabdomyomas may form sessile or pedunculated polyps on mucosal surfaces. Tumour sizes range from 1.0 to 12.5 cm (median: 3.0 cm). Classic fetal rhabdomyomas contain irregular bundles of immature skeletal muscle fibres within a myxoid background. Cells have features of fetal myotubes, i.e. spindly contours, central oblong nuclei, and eosinophilic cytoplasm. An intermediate (juvenile) subset of cases show greater cellularity, less myxoid stroma, cells with a smooth muscle phenotype, and differentiated rhabdomyoblasts
Adult rhabdomyoma
Most arise in the head and neck (e.g. in the parapharyngeal space, salivary glands, larynx, mouth, and soft tissue)
Adult rhabdomyomas form well-circumscribed, soft, nodular or lobular, deep-tan to reddish-brown masses. Tumour sizes range from 1.5 to 7.5 cm. They consist of large polygonal cells with abundant granular eosinophilic cytoplasm, small round vesicular nuclei, and well-defined cellular borders. The cytoplasm may be vacuolated (spider cells) or may contain rod-like inclusions or cross-striations. Mitoses are rare.
Benign triton tumor (aka neuromuscular choristoma)
An expansile intraneural mass characterized by the intimate interposition of mature skeletal muscle and nerve fibres within the endoneurium.
Classic cases involve large nerves or plexuses, most commonly the sciatic nerve and the brachial plexus. Patients present most often with progressive pain or features of peripheral neuropathy/plexopathy. Superimposed desmoid fibromatosis is seen in as many as 80% of cases in some studies.
To date, most cases of NMC and NMC-fibromatosis show CTNNB1 exon 3 (p.Thr41Ala and p.Ser45Phe) mutations, similar to those of sporadic desmoids.
Phosphaturic mesenchymal tumor
Morphologically distinctive neoplasms that cause tumour-induced osteomalacia in patients due to autonomous production of FGF23. May involve essentially any somatic soft tissue location.
PMTs are usually composed of bland, spindle to stellate cells, which produce an unusual hyalinized to smudgy-appearing matrix. A very well developed capillary network is typically present, with some cases also showing larger vessels arranged in a staghorn pericytoma-like pattern, or in a pattern resembling cavernous haemangioma. The matrix of PMT typically calcifies in an unusual grungy or flocculent fashion, sometimes forming flower-like slate-grey crystals, and in some instances it may contain foci closely resembling primitive cartilage or osteoid { 19609206 ; 14707860 ; 3545439 ; 16447065 }. Osteoclasts, fibrohistiocytic spindled cells, mature adipose tissue, microcystic change, and a peripheral shell of woven bone may be present. Mitotic activity and necrosis are usually absent.
In the jaws, PMTs with admixed epithelial (odontogenic) elements have been described. It is unclear whether these epithelial elements are neoplastic or entrapped/induced by the adjacent PMT.
IHC: Most PMTs express CD56, ERG, FGFR1, SATB2, and/or SSTR2A
Molecular: FN1-FGFR1 or FN1-FGF1 fusion
Apical fibroxanthoma
A dermal-based mesenchymal neoplasm of uncertain lineage. In a disease spectrum with pleomorphic dermal sarcoma in sun-damaged skin. Rarely, AFX is seen in the field of prior radiation therapy and in patients with immunosuppression.
Presents as a solitary, fast-growing, exophytic, dome-shaped nodule that is usually < 2 cm and often ulcerated. The neoplasms are red, flesh-coloured, or bluish-brown.
The histopathological criteria for the diagnosis of AFX must be used strictly, and the diagnosis of AFX should never be made on a biopsy only, or without the use of a panel of immunohistochemical antibodies. AFX represents an intradermal, usually symmetrical and well-circumscribed cellular neoplasm without involvement of the subcutis. Ulceration and collarette formation of the lateral hyperplastic epidermis are frequent. These cellular neoplasms are composed of sheets and fascicles of most often highly pleomorphic polygonal or histiocytoid cells, enlarged and atypical spindled and epithelioid cells, and variable numbers of atypical multinucleated tumour giant cells. Neoplastic cells contain enlarged atypical, vesicular, or hyperchromatic nuclei, and numerous mitoses (including atypical mitoses) are present.
By definition, tumour necrosis, lymphovascular and/or perineural invasion, and subcutaneous invasion are absent. Scattered inflammatory cells, numerous vessels, and areas of haemorrhage may be present.
Molecular: UV radiation signature mutations in TP53 have been found.
IHC: immunonegativity for keratins, S100, and SOX10, which should ALWAYS be performed to rule out alternatives.
Hemosiderotic fibrolipomatous tumor
HFLT is a slow-growing, sometimes painful subcutaneous (or, less often, deeper) soft tissue mass.
HFLT consists of lobules of mature fat admixed in variable proportions with fascicles of fibroblastic spindle cells containing haemosiderin, haemosiderin-laden macrophages, and osteoclast-like giant cells. In areas, the spindle cells are distributed more loosely in smaller numbers and often extend between individual adipocytes and around vessels. Occasional larger cells with atypical nuclei are sometimes present. Mitotic activity is low and necrosis is absent. Nuclear pseudoinclusions and large, ectatic, partially thrombosed vessels with perivascular hyalinization are sometimes present, leading to morphological overlap with pleomorphic hyalinizing angiectatic tumour.
May be on a spectrum with myxoinflammatory fibroblastic sarcoma, and hybrid lesions have been reported.
IHC: The spindled cells of HFLT are usually positive for CD34 and calponin.
Molecular: t(1;10), which does not result in a fusion transcript but always targets TGFBR3 in 1p22, demonstrates breakpoints in or near OGA (formerly MGEA5) in 10q24, and leads to transcriptional upregulation of neighbouring FGF8 and NPM3.
Juxta-articular myxoma
Benign myxoid soft tissue tumour morphologically similar to intramuscular/cellular myxoma (but lacking GNAS mutation), typically arising in the vicinity of large joints.
The tumour usually ranges in size between 2 and 6 cm, but tumours as large as 13 cm have been described. Affects soft tissue around large joints, most commonly the knee (~85% of cases).
The tumour is generally hypocellular and composed of bland spindle-shaped cells with uniform ovoid nuclei, inconspicuous nuclei, and palely eosinophilic cytoplasm embedded in a hypovascular myxoid stroma. Increased cellularity can be seen (similar to in cellular myxoma); however, mitoses are scarce. In the majority of cases, cyst-like spaces lined by a delicate fibrin layer or a thicker layer composed of collagen may be seen. The tumour is poorly circumscribed, demonstrating infiltration into the surrounding adipose or tendinous tissue. In a subset of cases, haemorrhage, chronic inflammation, and haemosiderin/fibrin deposition may be seen, probably due to trauma.
May express CD34 and/or SMA. S100 is negative. CD163-positive muciphages may be present.
Molecular: Lacks GNAS mutations.
Intramuscular myxoma
Intramuscular myxoma is a benign hypocellular soft tissue tumour composed of bland spindle-shaped cells embedded in a usually abundant myxoid and hypovascular stroma.
The most common locations are the large muscles of the thigh, shoulder, buttock, and upper arm. Intramuscular myxoma is a slow-growing painless mass.
Classic intramuscular myxoma is a cytologically bland, hypocellular lesion composed of uniform spindle to stellate-shaped cells with uniform small oval nuclei and indistinct palely eosinophilic cytoplasm embedded in an abundant extracellular myxoid stroma. Only sparse capillary-sized blood vessels are seen. Cystic change and vacuolation may be seen in the stroma. Necrosis and mitotic figures are not seen. At the edge of the lesion, infiltration of the tumour between and around individual skeletal muscle cells is often observed.
IHC: CD34+, associated CD163+ muciphages.
Molecular: Activating point mutation in GNAS (exons 8 and 9) is detected in > 90% of sporadic intramuscular and cellular myxomas
