Malignant soft tissue tumours

L.D.R. Thompson J.C. Fanburg-Smith

Fibrosarcoma

Definition

A malignant tumour of fibroblastic/myofi-broblastic phenotype.

ICD-O code 8810/3

Synonyms

Fibromyxosarcoma; chondromyxofibro-sarcoma.

Epidemiology

The incidence of sinonasal tract fibrosar-comas is difficult to determine because the diagnosis is often one of exclusion. These tumours are rare, accounting for <3% of all non-epithelial tumours. However, they are considered the second most common soft tissue sarcoma after rhabdomyosarcoma in the head and neck {168,345,349,826,1041,1317, 2511}. They occur in all ages, with a peak in the 5th decade. There is a 3:2 female:male gender predilection {168, 345,826,1041,1317,2438,2511}.

Etiology

A few patients have developed fibrosar-coma within the field of prior irradiation.

Localization

Most fibrosarcomas originate in one or more paranasal sinuses, while origination confined to the nasal cavity alone is less common {168,345,826,1041,1317, 2438}. The "infantile-type" fibrosarcoma in the sinonasal tract is exceedingly uncommon in the sinonasal tract and occurs near the choana {349,1041, 1317}.

Clinical features

Nearly all patients have nasal obstruction, often associated with epistaxis, while pain, sinusitis, nasal discharge, swelling, anosmia, and proptosis are less common. The median duration of symptoms is quite short.

Macroscopy

The tumours are smooth, nodular, pedun-culated, fungating or ulcerating. The lesions range in size between 2 and 8 cm, with the cut surface revealing a circumscribed but not encapsulated, fleshy, homogeneous white-tan to yellow-pink mass, variably firm dependent upon the collagen content. Necrosis and haemorrhage may be present in highergrade tumours.

Histopathology

The tumours are unencapsulated, sometimes sharply circumscribed, although often infiltrative and occasionally ulcerating. Bone invasion is common. Surface epithelial Invagination Into the tumour can be prominent, simulating an inverted papilloma. Spindle cells are arranged in compact fascicles, intersected by various amounts of delicate thin to dense keloid-like collagen. The cell bundles are arranged at acute angles to one another, occasionally giving rise to a "herringbone" or "chevron" pattern, while in most areas there is a more subtle fasciculation. A prominent storiform pattern is not seen. There is a marked variability in the cellu-larity within and between tumours. The cells are fusiform with a centrally placed hyperchromatic, needle-like nucleus surrounded by tapering cytoplasm which is often indistinct, creating a syncytial appearance to the fascicles. Most sinonasal tract fibrosarcomas are low grade. Nuclear pleomorphism is usually slight to moderate, but occasionally prominent. Mitotic figures are found in variable numbers. Haemorrhage and necrosis can be found in the poorly differentiated forms, with areas of myxoid degeneration. Focal osteo-cartilaginous differentiation has been described {168, 345,826,1041,1317,2438}. Fibrosarcomas are immunoreactive with vimentin, and sometimes focally with actin {1041}.

Fig. 1.37 Fibrosarcoma. A Short, angular intersections (herringbone or chevron) are most characteristic of a low grade fibrosarcoma. B Sweeping fascicles of minimally pleomorphic spindled cells can occasionally be seen. The overlying surface epithelium is unremarkable, including the presence of cilia.

Malignant Cells
Fig. 1.38 Malignant fibrous histiocytoma. Remarkably pleomorphic cells with atypical mitotic figures.

Differential diagnosis

The differential diagnoses include malignant fibrous histiocytoma, spindle cell carcinoma, spindle malignant melanoma, malignant peripheral nerve sheath tumour, monophasic synovial sarcoma, rhabdomyosarcoma, glomangiopericy-toma, desmoid fibromatosis, and nodular fasciitis {168,826,1041, 2332}.

Histogenesis

The (myo)fibroblast is considered the progenitor cell for these tumours.

Prognosis and predictive factors

Surgery is the treatment of choice, often followed by radiation therapy, yielding an overall long-term survival of 75% in low grade and localized tumours. The high incidence of recurrence (about 60%) is perhaps related to the complexity of the anatomy of the sinonasal tract and consequent difficulties of complete excision. Recurrence usually precedes metastasis, which occurs in about 15% of cases, most commonly to the lungs and bones and only rarely to lymph nodes. Poor prognostic factors include male gender, large tumour size, involvement of more than one contiguous site (nasal cavity and sinus, multiple sinuses), high histo-logic grade, and positive surgical margins {168,345,826,1041,1317,2438}.

Malignant fibrous histiocytoma

Definition

Malignant fibrous histiocytoma (MFH) is currently used as a diagnosis of exclusion for sarcomas composed largely of myofibroblasts or undifferentiated mes-enchymal cells.

ICD-O code 8830/3

Synonyms

Fibroxanthosarcoma, malignant fibrous xanthoma, myxofibrosarcoma, myxoid malignant fibrous histiocytoma

Epidemiology

Although once considered the most common sarcoma of adults, the frequency of its diagnosis has diminished since the introduction of immunohistochemistry has allowed assignment of some pleo-morphic sarcomas to specific sarcoma entities. Only 3% of MFH occur in the head and neck, with 30% of these arising in the sinonasal area {2187}. MFH rarely occurs in the nasopharynx {1032,1923}. Sinonasal MFH most commonly occurs in adults with a male predominance {2433}.

Etiology

Many sinonasal and nasopharyngeal MFH are a result of previous radiation, after a long latency period {1180,1345}.

Localization

The maxillary sinus is most commonly affected, followed by the ethmoid sinuses and nasal cavity, whereas the frontal and sphenoid sinuses and nasopharynx are affected far less commonly {279,536, 581,1032,1923,1936,2256,2426,2433}.

Clinical features

Symptoms include mass, swelling, facial pain, loose teeth, epistaxis, and nasal obstruction {279,1707,2015,2187,2426, 2433}.

Macroscopy

Tumours are generally smooth, nodular or pedunculated (polypoid), with a number being fungating or ulcerating. The cut surface reveals a fleshy, homogeneous white-tan to yellow-pink mass with necrosis and haemorrhage, measuring up to 8 cm in maximum dimension {714}.

Tumour spread and staging

Sinonasal MFH can directly extend into nasopharynx, orbit, and pituitary fossa {1032,1707} and commonly metastasizes to lungs, bones, liver, {1707,2426} and only rarely to lymph nodes {279,1032, 1707}.

Histopathology

Sinonasal MFH are generally infiltrative and ulcerative, but can occasionally be circumscribed. Pleomorphic MFH, the most frequent morphologic subtype of MFH in the sinonasal tract, is characterized by spindled to pleomorphic cells in a storiform growth pattern, with easily identified mitotic figures, including atypical forms, and necrosis. The cells are fusiform with tapering indistinct cytoplasm. Tumour giant cells with multiple nuclei may be found.

Immunohistochemistry

MFH are usually positive for vimentin and focally for actins. Importantly, MFH is a diagnosis of exclusion and is generally negative for desmin, skeletal muscle specific markers, S100 protein, HMB-45, epithelial markers and lymphoid markers.

Differential diagnosis

The differential diagnoses include fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, monophasic synovial sarcoma, malignant peripheral nerve sheath tumour, spindle cell carcinoma, spindle cell malignant melanoma and anaplastic large cell lymphoma.

Prognosis and predictive factors

Compared with other anatomical sites, MFHs of the head and neck generally have a slightly lower rate of recurrence and metastasis {133}.

Leiomyosarcoma

Definition

A malignant tumour of smooth muscle phenotype.

ICD-O code

8890/3

Epidemiology

Only a small number of sinonasal leiomyosarcomas have been reported {151,824,840,1144,1395,1416,1529, 2147,2240,2553}, accounting for <1% of all non-epithelial tumours. They occur in all ages, with a peak in the 6th decade (mean, 53 years) without a gender difference.

Etiology

There are a few reported cases with a prior history of radiation {824,1416,2147} or chemotherapy (cyclophosphamide specifically) {1416,2147}.

Localization

Involvement of both the nasal cavity and paranasal sinuses is more common than involvement of the nasal cavity alone {824,840,1144,1395,1416,1529,1745}.

Clinical features

Nearly all patients have nasal obstruction, frequently associated with epistaxis and pain, while nasal discharge, swelling, and blurred vision are less common. The duration of symptoms is usually long {824,840,1144,1395,1416, 1529,2147,2240,2553}. There is usually no lymphadenopathy. Plain radiographs show opacification of the nasal cavity or sinus(es), often suggesting sinusitis {1144,1395,1529,2553}.

Macroscopy

These tumours range in size up to 7 cm, with an average of about 4 cm. They are more likely infiltrative than circumscribed, and occasionally polypoid. The surface is typically ulcerated and crusted. These bulky tumours have a cut surface which reveals a soft to firm, grey-white and fleshy appearance. Haemorrhage, necrosis and cystic change are common.

Histopathology

Leiomyosarcomas are infiltrative neoplasms accompanied by surface ulceration. Bone or cartilage invasion is more frequent than surface or seromucinous gland invasion. Leiomyosarcomas are

Leiomyosarcoma

Definition

A malignant tumour of smooth muscle phenotype.

Malignant Neoplasm Definition
Fig. 1.39 Leiomyosarcoma. A spindle cell neoplasm with "cleared" cytoplasm, immediately adjacent to the nucleus, is seen below an intact surface mucosa. Mitotic figures are seen.
Haemangiopericytoma

iY" i

Fig. 1.40 Leiomyosarcoma. A A high power shows short, "cigar-like" nuclei with small cytoplasmic clearing adjacent to the nucleus. There are atypical mitotic figures. B Desmin reactivity in the remarkably pleomor-phic tumour cells can help to confirm the smooth muscle differentiation.

composed of right-angle intersecting bundles of spindle cells. Palisading, storiform and "haemangiopericytoma-like" patterns can occur. The tumours are hypercellular, but coagulative tumour necrosis and haemorrhage can create a hypocellular appearance. The tumour cells have elongated, vesicular to hyperchromatic, lobulated or indented nuclei with blunt ends ("cigar-shaped"). The cytoplasm is fibrillary and eosinophilic, with frequent perinuclear vacuolation. Mitoses, both typical and atypical, are present to a variable degree {824,840, 1144,1395,1416,1529, 2147,2240,2553}.

Histochemistry and immunoprofile

Intracytoplasmic glycogen can be demonstrated with a PAS stain. Masson trichrome stain demonstrates red, longi-

tudinally oriented parallel fibrils within the cytoplasm. Tumour cells are diffusely and strongly immunoreactive for vimentin, actin (smooth muscle or muscle-specific), desmin and h-caldesmon. There is generally no reactivity with keratin, CD34, CD117, S-100 protein or HMB-45 {1144,1395,2702}. The Ki-67 index is usually >15% {1144}.

Electron microscopy

Electron microscopy reveals variable features of smooth muscle cells, including myofilaments arranged in parallel arrays, dense bodies within the filaments, cell junctions, pinocytotic vesicles and basal lamina {1395,1529,1933}.

Differential diagnosis

The differential diagnoses include sinonasal glomangiopericytoma, periph-

Alveolar Nasal
Fig. 1.41 Rhabdomyosarcoma A Nasal alveolar rhabdomyosarcoma, with typical alveolar pattern. B The tumour cells are ovoid and have hyperchromatic nuclei and scant eosinophilic cytoplasm.

eral nerve sheath tumour, fibrosarcoma, spindle cell carcinoma and melanoma {824,840,1144,1395,1416,1529,2147,22 40,2553,2603}.

Genetic susceptibility

There are isolated cases of children with leiomyosarcomas who have preexisting hereditary retinoblastomas {627}.

Prognosis and predictive factors

About half of the reported cases develop local recurrence, often within one year, and nearly 1/3 of these patients will subsequently develop metastasis (mostly to the lungs and liver). Complete surgical excision is difficult to achieve, and radiation and chemotherapy are used with variable results. {824,1416,2501}. Poor prognostic factors include involvement of more than one contiguous site, large tumour size (>5 cm), high mitotic count (>20/10 high power field), tumour necrosis, and tumour stage {824,840, 1144,1395,1416,1529,2147,2240,2553}.

Rhabdomyosarcoma

Definition

A malignant tumour of skeletal muscle phenotype.

ICD-O code 8900/3

(Also see subtypes: 8910/3, 8912/3, 8920/3, 8901/3 in WHO Tumours of Soft Tissue)

Synonyms

Myosarcoma, malignant rhabdomyoma, rhabdosarcoma, embryonal sarcoma, rhabdomyoblastoma

Epidemiology

Approximately 40% of rhabdomyosarco-mas occur in the head and neck {1978}, with about 20% in the nasal cavity, nasopharynx, and nasal sinuses {2745}. Rhabdomyosarcoma is the most common sarcoma in childhood. The embryonal subtype predominates in children, while the alveolar subtype predominates in adults {825,1273}. The pleomorphic subtype is rare {836,837}. There is an overall slight male predominance {825}.

Localization

The nasopharynx is more commonly involved than the sinonasal tract {326,724}. In adults, rhabdomyosarcoma is more common in the ethmoid sinuses, followed by the maxillary sinuses and nasopharynx {1856}.

Clinical features

Signs and symptoms include difficulty in breathing, epistaxis, facial swelling, visual disturbances, and sinusitis often of short duration. Tumours may appear as a large, polypoid sinonasal mass or may occasionally protrude as a gelatinous mass from the nares {825}. CT and MRI imaging delineate the size and extent of the tumour {1453,2846}. The botryoid type shows grape-like rings and heterogeneous enhancement {980}.

Macroscopy

The embryonal subtype is generally poorly circumscribed, fleshy, pale and tan; the spindle cell variant is firm, fibrous, and tan-yellow with a whorled cut surface. The botryoid variant has a grape-like or polypoid appearance

{825}. The alveolar subtype is fleshy to firm tan-grey.

Tumour spread and staging

These tumours often spread to contiguous sites including base of the skull, temporal bones, and orbit {724,825}. About 40% metastasize to lymph nodes, bones, and lungs, and less commonly bone marrow, soft tissue, liver and brain {1441,1856}. The tumours are staged according to the Intergroup Rhabdomyosarcoma Study. Group I includes local disease, Group II residual disease or local spread, Group III incomplete resection or biopsy with gross residual disease, and Group IV metasta-tic disease at onset {613}. Most adult sinonasal and nasopharyngeal rhab-domyosarcomas are staged as Group III or IV at presentation {1856}.

Histopathology

Embryonal rhabdomyosarcoma has round to spindled cells with hyperchromatic nuclei. Larger rhabdomyoblasts with eosinophilic cytoplasm are usually identified, but cross striations are difficult to recognize. Myxoid stroma is common. The spindle cell variant, characterized by spindled cells in fascicular to storiform growth patterns, can be deceptively bland. The botryoid variant is polypoid with a submucosal hypercellular cambium layer, a myxoid hypocellular zone, and a deep cellular component. Alveolar rhabdomyosarcoma typically has fibrous septa separating clusters of loosely cohesive groups of small to medium round tumour cells with hyperchromatic nuclei and scant eosinophilic cyto

Fig. 1.42 Sinonasal rhabdomyosarcoma. A This macroscopic image demonstrates the similarity between a sinonasal polyp and a rhabdomyosarcoma. B Irregular islands of tumour in stroma may mimic carcinoma. Desmin and skeletal muscle markers can aid in the diagnosis of rhabdomyosarcoma.

Hlal

Fig. 1.42 Sinonasal rhabdomyosarcoma. A This macroscopic image demonstrates the similarity between a sinonasal polyp and a rhabdomyosarcoma. B Irregular islands of tumour in stroma may mimic carcinoma. Desmin and skeletal muscle markers can aid in the diagnosis of rhabdomyosarcoma.

plasm. Multinucleated giant cells with overlapping peripheral nuclei are often present. The solid variant grows in sheets and lacks septa. Rarely, the tumour can be composed exclusively or predominantly of clear cells. A mixed alveolar and embryonal pattern may occur.

Mitotic figures are usually easy to identify. Pleomorphism is occasionally observed focally. After treatment, there is often increased cytodifferentiation, with the cells exhibiting abundant eosinophilic fibrillary cytoplasm {2644}. Pleomorphic rhabdomyosarcoma is rare and uncommon in this location.

Immunohistochemistry

There is immunoreactivity for desmin, muscle specific actin, myoglobin, fast myosin, nuclear MyoD1 and nuclear myogenin (skeletal muscle myogenin, myf4) {2619}. CD99 can be positive in 16% of cases {1084}.

Electron microscopy

Electron microscopy shows some degree of skeletal muscle differentiation ranging from well-formed Z-bands to incomplete sarcomeres with thick and thin filaments and ribosome-myosin complexes {724,837}.

Differential diagnosis

The differential diagnoses of embryonal rhabdomyosarcoma include sinonasal polyp with stromal atypia {1840} and various sarcomas. The differential diagnoses of alveolar rhabdomyosarcoma include various round blue cell tumours, including lymphoma, sinonasal undiffer-entiated carcinoma, small cell carcinoma of neuroendocrine type, mesenchymal chondrosarcoma, PNET/Ewing sarcoma, olfactory neuroblastoma, and mucosal malignant melanoma.

Somatic genetics

Embryonal rhabdomyosarcoma shows allelic loss at 11p15 {271,925}. Alveolar rhabdomyosarcoma has a consistent translocation, usually t(2:13) (PAX3-FKHR), or less commonly t(1;13) (PAX7-FKHR) which can be performed on paraffin-embedded sections {141}.

Genetic susceptibility

Germline mutations of TP53 in Li-Fraumeni syndrome are found in some children with rhabdomyosarcoma.

Prognosis and predictive factors

Prognosis is determined by patient age, histologic subtype, and tumour clinical group {2123}. Younger patients have a more favourable prognosis than older r. *

Pax7 Paraffin
* M * f * Î C

Fig. 1.43 A Alveolar rhabdomyosarcoma of nasal cavity. After chemotherapy, domyosarcoma demonstrates remarkably atypical spindle cells with small amounts there is increased cytodifferentiation to rhabdomyoblasts. B An embryonal rhab-of eosinophilic cytoplasm.

Lymph node and distant metastasis is not common at presentation.

Macroscopy

The tumours range up to 8 cm, with a mean of about 4 cm. They are nodular, polypoid and morulated, soft and friable, purple to red, often ulcerated with associated haemorrhage or clot and necrosis {823,1848,2633,2795,2812}.

Histopathology

Most sinonasal angiosarcomas are histologically low-grade. They infiltrate the adjacent tissues and bone, accompanied by necrosis and haemorrhage. They comprise tortuous anastomosing vascular channels that dissect the stroma, capillary-sized vessels and cavernous vascular spaces. The lining endothelial cells range from flat to plump spindly to epithelioid, and often form papillary tufts. Intracytoplasmic vacuoles (neolumen), often containing erythrocytes, are characteristic of the epithelioid variant. The degree of nuclear pleomorphism is variable. Mitotic figures, including atypical forms, are variably present {823,1848, 2633,2795,2812}.

Immunohistochemistry

Angiosarcomas are immunoreactive for CD34, CD31, Factor VIII R-Ag and vimentin, and focally keratin (especially the epithelioid variant) and actin {2812}.

Differential diagnosis

The differential diagnoses include granulation tissue, intravascular papillary

Squamous Cell Tissue
Fig. 1.45 Angiosarcoma. A A richly vascularized tumour abuts the cartilage. Many ramifying vascular channels are filled with erythrocytes. B A benign duct (right lower) is surrounded by a vascular neoplasm with "neolumen" formation and intraluminal erythrocytes. Note the mitotic figure.
Alveolar Rhabdomyosarcoma Left Hand
Fig. 1.44 Alveolar rhabdomyosarcoma showing scant cytoplasm surrounding atypical nuclei. There are small areas of eccentric eosinophilic cytoplasm (left). The tumour cells are strongly immunoreactive to desmin (right).

patients In all rhabdomyosarcoma subtypes. Currently, the 5-year survival Is 4469%, and 90% for clinical Group I disease {322,1084}. Adults have a poor prognosis, with 5-year survival of <10% {1841,1856}. Embryonal rhabdomyosar-coma has a better prognosis than alveolar rhabdomyosarcoma {2123}. Botryoid and spindle cell variants {346} have a better prognosis than embryonal rhab-domyosarcoma. Furthermore, alveolar rhabdomyosarcomas with PAX7/FKHR are thought to have better prognosis than PAX3/FKHR tumours {1298}.

Angiosarcoma

Definition

A malignant neoplasm of vascular phe-notype whose constituent tumour cells have endothelial features.

ICD-O code 9120/3

Synonyms

Malignant haemangioendothelioma; malignant angioendothelioma; lymphan-giosarcoma, haemangiosarcoma.

Epidemiology

Angiosarcoma is uncommon, accounting for less than 1% of all sinonasal tract malignancies {89,1603,1640,1848}. They occur in all ages, with a peak in the 5th decade, and a male predilection (male:female = 2:1). Females tend to be younger at presentation by up to a decade {823,1848,2633,2795,2812}.

Etiology

Radiation exposure {1556,1603,1848}, Thorotrast, arsenic and vinyl chloride are reported risk factors {2795}.

Localization

The maxillary sinus is most frequently affected. Other sites that may be involved primarily or secondarily include the nasal cavity and other paranasal sinuses {823,1848,2633,2795,2812}.

Clinical features

Patients present with recurrent epistaxis, profound pallor, a mass lesion, pain (including headache, otalgia, toothache), nasal obstruction, sinusitis, nasal discharge (often described as foul-smelling and blood tinged), paraesthesia and/or loose teeth. The duration of symptoms ranges from weeks to months, but is generally short (median, 4 months).

endothelial hyperplasia, haemangioma, nasopharyngeal angiofibroma, angiolym-phoid hyperplasia with eosinophilia, glo-mangiopericytoma, Kaposi sarcoma, malignant melanoma, carcinoma and large cell lymphoma {30,1388,1976, 2469,2764}.

Prognosis and predictive factors

Patients are usually treated by surgical resection with radiation and/or chemotherapy. Recurrences are common (50%), likely due to incomplete excision or possible multifocality. Metastasis is uncommon, and the predilection sites are the lung, liver, spleen, and bone marrow {1976}. The outcome is more favourable compared with the almost uniformly fatal outcome for cutaneous and soft tissue angiosarcomas {823, 1848,2633,2795,2812}

Malignant peripheral nerve sheath tumour

Definition

A malignant tumour of nerve sheath phe-notype.

ICD-O code

9540/3

Synonyms

Neurogenic sarcoma, malignant schwannoma, neurofibrosarcoma.

Epidemiology

Malignant peripheral nerve sheath tumours (MPNSTs) comprise 2-14% of all r •

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