Small round cell neoplasms

The Ewing family of tumors comprises small round cell neoplasms of bone and soft tissue that are, in part, defined by a particular chromosomal aberration [t(ll 22)] and variants thereof. Over the past 15 years, it has become clear that ES and peripheral PNET are part of the same spectrum of neoplastic proliferations. Besides the karyotypic marker just mentioned, both of those tumor types also show neuroectodermal features in tissue culture and similarities in proto-oncogene expression. As classically defined, ES was distinguished from PNET by an absence of pseudorosettes and the lack of ultrastructurally or immunohistochemically detectable neuroectodermal features. However, this diagnostic separation is now considered to be antiquated and has been abandoned. 

Katz RL, Quezado M, Senderowicz AM, et al. An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript. Hum Pathol. 1997 28 502-509. 

Mierau GW, Berry PJ, Orsini EN. Small round cell neoplasms can electron microscopy and immunohistochemical studies accurately classify them Vltrastruct Pathol. 1985 9 99-111. 

The small round cell tumors of soft tissue (Fig. 4.9 see Table 4.4) compose a heterogeneous group of neoplasms that predominate in childhood and adolescence and share similar morphologic features. Rhabdomyosarcoma, PNET/ES, and lymphoma/leukemia are the prototypic members of this group. Another entity that may be confused with PNET is the intra-abdominal desmoplastic small round cell tumor. 

The term polyphenotypic small round cell tumor seems most appropriate to describe the general attributes of these lesions. The desmoplastic small round cell tumor (DSRCT) is the best-recognized representative of this group. It is characterized by an EWS/WTl chimeric transcript, and is a morphologically distinctive neoplasm that is characterized by reactive fibrosis surrounding discrete nests of tumor cells (Fig. 4.15). DSRCT has a relatively complicated immunoprofile. 

Hematopoietic neoplasms only rarely present as soft tissue masses, and this phenomenon is particularly unusual in pediatric patients in whom other forms of small round cell tumors are most common. Because of the virtually ubiquitous presence of CD45 in hematopoietic cells and its extremely high degree of specificity, that marker is very valuable in this context. Not all antibodies raised against CD45 identify determinants that survive routine tissue processing, but the monoclonal antibody cocktail PD7/26 2B11 (see Table 4.3) is indeed active in paraffin sections. 

In addition to epithelial neoplasms, a number of sarcomas, CNS tumors, small round cell tumors, and a few germ cell tumors may be positive with EMA. These tumors include malignant nerve sheath tumors, synovial sarcoma, leiomyosarcoma, malignant fibrous histiocytoma, epithelioid sarcoma, and chordoma. With the exception of the last two tumors mentioned, EMA immunostaining is focal. 

Choroid plexus neoplasms and meningiomas show strong membranous EMA immunostaining. Germ cell tumors are largely negative except for variable EMA immunostaining in choriocarcinoma and teratoma, whereas the epithelial small round cell tumors... 

Many of the tumors of the nasal cavity and paranasal sinuses fall under the category of round cell neoplasms. Among these are olfactory neuroblastoma, sinonasal undifferentiated carcinoma, malignant melanoma, neuroendocrine carcinoma-small cell neuroendocrine carcinoma, malignant lymphoma, extramedullary plasmacytoma, invasive-ectopic pituitary adenoma, rhabdomyosarcoma, and Ewing s sarcoma (ES)-peripheral neuroectodermal tumor (ES/ PNET). But there is also a host of other epithelial lesions that are unique to the sinonasal tract. 

Desmoplatic small round cell tumors occur primarily in the abdominal cavity.The neoplasms characteristically show immunostaining for desmin (a dotlike pattern), WTl, keratin, neuron-specific enolase, CD99, and actin. They also show the EWS-WTl gene fusion transcript. A desmoplastic, small, round cell tumor was reported primary in the lung by Syed and coworkers.Ultrastructurally, this tumor showed intracytoplasmic whorls of intermediate filaments, presumably desmin. A desmoplastic, small, round cell tumor was also reported as a primary neoplasm in the pleura. 

Mesothelin is a 40-kD glycoprotein of unknown function that is strongly expressed in mesothelial cells, ovarian serous cells, and pancreatic-bile duct cells. Using monoclonal antibody 5B2, Ordonez found it to immu-nostain normal mesothelial cells, mesotheliomas, non-mucinous ovarian carcinomas, and occasionally other neoplasms. Ordonez concluded that mesothelin staining could be used to diagnose mesotheliomas, although it was expressed in 14 of 14 ovarian carcinomas, 12 of 14 pancreatic ductal adenocarcinomas, 7 of 12 desmoplastic small round cell tumors, and 9 of 9 synovial sarcomas. Therefore, this antibody should be interpreted carefully. 

EWS/PNET shows a morphologic spectrum from a primitive small round cell tumor to a predominantly round cell neoplasm with a lobular architecture and pseudorosette formation. 

Wilms tumor gene (WTl) is a tumor suppressor gene present on chromosome 11. It was first reported as a candidate for main gene in the development of Wilms tumor. The immunohistochemical expression of WTl was demonstrated in a variety of neoplasms. A majority of epithelioid mesotheliomas and a small percentage of sarcomatoid mesotheliomas express WTl. Strong immunoreactivity for WTl is demonstrated in desmoplastic, small round-cell tumors (DSRT). WTl represents an... 

The histopathologic appearance of MRT is a densely cellular neoplasm composed of sheets or cords of cells with large vesicular round or oval nuclei, prominent central eosinophilic nucleoli, and abundant eccentric eosinophilic cytoplasm (Fig. 17.26). Histologic variability is typical, and some cases have smaller numbers of characteristic rhabdoid cells or display a primitive small blue cell pattern, a myxoid background, a lack of cellular cohesion, increased collagen deposition between bands of tumor cells, and scattered non-neoplastic osteoclastlike giant cells. Occasionally cases have focal epithelial areas. Mitoses are frequent. Electron microscopy reveals cytoplasmic whorls of intermediate filaments, which correspond to the eosinophilic globules of cytoplasm in the classic rhabdoid cells. 

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