Ovarian involvement by the intra-abdominal desmoplastic small round cell tumor with divergent differentiation: a report of three cases.

Three girls, one 14 and two 15 years of age, with the recently described neoplasm that has been designated "intra-abdominal desmoplastic small round cell tumor with divergent differentiation," and ovarian involvement at presentation are described. In two cases the ovarian tumor was initially thought to be the primary neoplasm. In all cases there was extensive extraovarian tumor at the time of presentation. The ovarian involvement was bilateral in two cases and unilateral in the third. Microscopic examination showed prominent nodular growth within the ovaries. The tumors were characterized predominantly by nests of small cells with hyperchromatic nuclei and scant cytoplasm separated by a prominent desmoplastic stroma. A few tubules containing mucinous secretion were present in one case. On immunohistochemical staining many of the tumor cells stained positively for cytokeratin, epithelial membrane antigen, desmin, and vimentin. Staining for neuron-specific enolase was present in two cases but was conspicuous in only one of them. Leu-7 was expressed by the tumor cells in two cases, and S-100 protein by one, giving further support to the possibility of neuroectodermal differentiation within some of these neoplasms. The two cases studied by electron microscopy both showed frequent intercellular junctions, basal lamina, cytoplasmic filaments, and sparse, small dense granules of either neuroendocrine or lysosomal type. Paranuclear aggregates of filaments were found in one case and cellular processes were prominent in the other case. The differential diagnosis in these cases was extensive and included a number of small cell tumors that may involve the ovary, either primarily or secondarily, in young females. The desmoplastic small round cell tumor should be considered in such cases when the appearances on routine examination are consistent with the diagnosis, and appropriate immunohistochemical stains should be performed to confirm the diagnosis.     

Desmoplastic small cell tumors of the peritoneum coexpressing mesenchymal and epithelial markers.

Desmoplastic small cell tumors arising diffusely within the abdomen and lacking an apparent organ of origin are rare. Most previously reported cases occurred in children, but young adult patients also have been described. Light microscopic examination shows the tumors to be composed of nests of small cells surrounded by an abundant desmoplastic stroma. Immunohistochemical findings reveal multidirectional differentiation with coexpression of cytokeratin, milk fat globule, neuron-specific enolase, Leu-7, desmin, and vimentin. Electron microscopic examination demonstrates paranuclear condensations of intermediate filaments. The authors describe two patients who died of their disease, despite aggressive chemotherapy and surgical intervention.     

Intra-abdominal Desmoplastic Small Round Cell Tumor of the Peritoneum in a Young Man

The desmoplastic small round cell tumor (DSRCT) has a predilection for involvement of the peritoneal surfaces of young adult men. The tumor has an extremely poor prognosis: despite aggressive therapy the patients usually die of disease within the first 2 years following diagnosis. The present report details the pathologic features of a pelvic tumor, which proved to be a DSRCT, arising in a previously healthy 24-year-old man. The light microscopic features were typical of a DSRCT—the tumor cells were small and round, had inconspicuous cytoplasm, and were grouped into distinctive islands and cords that were dispersed in a fibrous stroma. The immunohistochemical features were likewise characteristic of DSRCT in that the tumor cells were positive for cytokeratin, vimentin, epithelial membrane antigen, and desmin. Ultrastructurally, the tumor cells were distinguished by an abundance of intercellular junctions, cytoplasmic lipid droplets, cytoplasmic intermediate filaments, and an absence of surface microvilli. Recognition of this tumor type is important in view of both its clinical features (extremely poor prognosis despite therapy) and its potential to shed some light on the nature of the family of lesions that has traditionally been classified by light microscopists as small round cell tumors.     

Intra-abdominal Desmoplastic Small Round Cell Tumor of the Peritoneum in a Young Man

The desmoplastic small round cell tumor (DSRCT) has a predilection for involvement of the peritoneal surfaces of young adult men. The tumor has an extremely poor prognosis: despite aggressive therapy the patients usually die of disease within the first 2 years following diagnosis. The present report details the pathologic features of a pelvic tumor, which proved to be a DSRCT, arising in a previously healthy 24-year-old man. The light microscopic features were typical of a DSRCT—the tumor cells were small and round, had inconspicuous cytoplasm, and were grouped into distinctive islands and cords that were dispersed in a fibrous stroma. The immunohistochemical features were likewise characteristic of DSRCT in that the tumor cells were positive for cytokeratin, vimentin, epithelial membrane antigen, and desmin. Ultrastructurally, the tumor cells were distinguished by an abundance of intercellular junctions, cytoplasmic lipid droplets, cytoplasmic intermediate filaments, and an absence of surface microvilli. Recognition of this tumor type is important in view of both its clinical features (extremely poor prognosis despite therapy) and its potential to shed some light on the nature of the family of lesions that has traditionally been classified by light microscopists as small round cell tumors.     

Miscellaneous rare paratesticular tumors

A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed.     

Small cell carcinoma of the kidney: a case report and review of the literature

Small cell carcinoma is a malignant tumor composed of small cells with a diffuse growth pattern. It has immunohistochemical and ultrastructural features of both neuroendocrine and epithelial neoplasms. These tumors constitute 10% to 20% of malignant tumors in the lung, which is their most frequent site. They have been described in other extrapulmonary sites, where they are defined using the same criteria as used in the lung. These tumors are rarely found in the genitourinary tract. Fewer than 30 cases have been reported in the kidney. The differential diagnosis mainly includes other small round cell tumors and metastatic small cell lung carcinoma. We present and discuss a primary small cell carcinoma of the kidney (to our knowledge the 9th to be reported in the literature), which we studied with light microscopy, immunohistochemistry, electron microscopy, and, for the first time, flow cytometry.     

Nodule formation and desmoplasia in medulloblastomas-defining the nodular/desmoplastic variant and its biological behavior

Among the variants of medulloblastoma in the current WHO classification of nervous system tumors, the desmoplastic variant, which has been reported to constitute 5%-25% of pediatric medulloblastomas, is defined by its nodular collections of neurocytic cells bounded by desmoplastic internodular zones. We have studied the frequency, morphological features and biological behavior of medulloblastomas in two contemporaneous SIOP/UKCCSG trial cohorts of children with medulloblastomas, CNS9102 (n = 315) and CNS9204 (n = 35), focusing on tumors with nodular and desmoplastic phenotypes. In children aged 3-16 years (CNS9102), the nodular/desmoplastic medulloblastoma represented 5% of all tumors, while in infants aged <3 years (CNS9204) this variant represented 57% of medulloblastomas. Using iFISH to detect molecular cytogenetic abnormalities in medulloblastomas with a nodular architecture, we demonstrated distinct genetic profiles in desmoplastic and non-desmoplastic (classic and anaplastic) tumors; in particular, abnormalities of chromosome 17 occurred in the latter, but not the former. Significantly different outcomes were demonstrated for classic, nodular/desmoplastic and large cell/anaplastic medulloblastomas in both cohorts. In conclusion, the nodular/desmoplastic medulloblastoma appears to have clinical, genetic and biological characteristics that set it apart from other variants of this tumor.     

Biphasic intra-abdominal desmoplastic small cell tumor in a patient with proximal spinal muscular atrophy

A case is reported of intra-abdominal desmoplastic small cell tumor (IDSCT) with biphasic histologic features in a patient with proximal spinal muscular atrophy. The tumor was composed of small epithelial cell nests with spindle cell sarcomatous areas. Both areas were surrounded by a desmoplastic stroma. Immunohistochemical studies revealed reactivity for low molecular weight cytokeratin, epithelial membrane antigen, vimentin, desmin and Leu-7 in both areas. Electron microscopic examination demonstrated paranuclear aggregates of intermediate filaments, zonula adherens and basement membrane-like material in the epithelial cells, while spindle cells in the tumor had fewer intracytoplasmic organelles. However, intermediate or transitional forms of both types of tumor cells were frequently observed. Although IDSCT are known to express multi-phenotypes immunohistochemically, attention should be paid to the broad spectrum of cell morphology in these tumors.     

Hyalinizing clear-cell carcinoma of salivary glands in fine-needle aspiration

Hyalinizing clear-cell carcinoma (HCCC) is a recently described distinctive salivary gland neoplasm. Because of its cytoplasmic clearing and the bland nuclear features, HCCC resembles other tumors. The authors describe the cytomorphologic features of four cases of HCCC in fine-needle aspirates (FNA) and discuss the differential diagnosis. Fine-needle aspirates from 4 patients with primary HCCC of minor salivary glands were reviewed. Smears were stained with Diff-Quik and Papanicolaou stains. The cytologic features of the epithelial and the stromal components were analyzed. Cell blocks were prepared, and findings were correlated with prior or subsequent surgical specimens in each case. The smears contained numerous cohesive small and large epithelial cell groups and sheets which had sharp outlines and showed focal nuclear overlapping. The cells had uniform round to ovoid nuclei, granular chromatin, and small nucleoli. The abundant, well-defined cytoplasm was clear in many cells but denser in others. No myoepithelial cells or hyaline globules were identified. HCCC seems to have characteristic cytomorphologic findings on FNA smears. Because these cytologic features are not specific, and overlap with those of a number of salivary gland neoplasms that contain clear cells, a high level of suspicion, clinico-pathologic correlation, and examination of cell blocks are necessary to suggest the diagnosis. A diagnosis of HCCC by FNA was suspected in 3 of the 4 cases reported here.     

Carcinoma of the breast with choriocarcinomatous features

Choriocarcinomatous differentiation has been described in tumors arising from many organs including lung, rectum, colon, stomach, bladder, and rarely breast. Mammary carcinoma with choriocarcinomatous features is a rare variant of breast metaplastic carcinoma characterized by malignant cells morphologically resembling choriocarcinoma cells in which reactivity with human placental lactogen and human chorionic gonadotropin can be demonstrated by immunohistochemistry. The characteristic syncytiotrophoblast-like giant cells seen in these neoplasms are more commonly associated with moderately to poorly differentiated carcinomas with or without a clear-cut mesenchymal component. Most of the reported cases have behaved very aggressively. The reason for this poor prognosis remains unclear. Because of the small number of cases, special treatment protocols have not been developed and these patients are treated surgically and with the standard chemotherapeutic agents available for other types of carcinoma of the breast. Pathologically, these tumors must be distinguished from metastatic choriocarcinoma to the breast.     

Solid-pseudopapillary tumor of the pancreas: a neoplasm with distinct and highly characteristic cytological features

The solid-pseudopapillary tumor of the pancreas (SPTP) is an unusual low-grade malignant epithelial tumor affecting predominantly adolescent girls and young women. Although approximately 500 cases of SPTP have been described in the last 40 yr, its pathogenesis remains uncertain. However, the clinical features of this neoplasm are very characteristic and SPTP must be suspected in any young woman with a cystic or partially cystic pancreatic mass. In this report, we describe the cytologic features of seven cases of SPTP investigated by preoperative fine-needle aspirates. The analysis of the cytologic features in these cases and in 43 cases collected from the literature reveals that they are highly characteristic and quite distinct from those of other cystic or solid tumors of the pancreas. On this basis, a cytologic diagnosis of SPTP may be rendered with great confidence, not only in clinically typical examples, but also in unusual presentations, such as in older patients, in males, in ectopic locations, and in metastatic sites.     

Correlation of loss of heterozygosity at chromosome 9q with histological subtype in medulloblastomas.

Patients with the nevoid basal cell carcinoma syndrome (NBCCS) are at increased risk for medulloblastomas as well as for basal cell carcinomas. The gene for NBCCS has been mapped to chromosome 9q22.3-q31 by linkage analysis, and loss of heterozygosity (LOH) in this region has been demonstrated in approximately one-half of sporadic basal cell carcinomas. In the present study, LOH for chromosome 9q22.3-q31 microsatellite markers was investigated in medulloblastomas occurring among children with NBCCS and in sporadic medulloblastomas. Histologically, all 3 NBCCS medulloblastomas were noted to have a desmoplastic phenotype, and LOH was detected in both of the 2 cases for which microsatellite markers were heterozygous in normal tissues. LOH was also detected in a subset of sporadic medulloblastomas, each of which were found to display the desmoplastic phenotype. In all, 3 of the 6 sporadic desmoplastic tumors showed LOH, whereas LOH was not seen in any of the 11 sporadic, non-desmoplastic medulloblastomas studied. Additionally, desmoplastic tumors lacking detectable LOH each showed histological features of so-called cerebellar neuroblastoma, a subgroup of desmoplastic medulloblastoma with extensive neuroblastomatous differentiation. The data are consistent with a role for inactivation of a tumor suppressor gene at chromosome 9q in the development of medulloblastomas in patients with NBCCS and of sporadic medulloblastomas characterized by a desmoplastic phenotype similar to that found in patients with NBCCS. Restriction of chromosome 9q loss to non-neuroblastomatous desmoplastic tumors suggests that this variant of medulloblastoma maybe pathogenetically distinct from tumors having other histological phenotypes.     

Carcinosarcoma of the urinary bladder--an aggressive tumor with diverse histogenesis. A clinicopathologic study of 4 cases and review of the literature

OBJECTIVE: Carcinosarcomas of urinary bladder are rare malignant neoplasms. Seventy-eight cases have been previously described. The histologic composition of these tumors is variable, but diagnosis requires the presence of both epithelial and mesenchymal malignant components. We report 4 additional cases, with an emphasis on unusual histologic features. METHODS: Histologic and immunohistochemical examinations were performed on bladder tumors from 4 patients. Clinicopathologic features of previously reported and current cases were reviewed and summarized. RESULTS: Four patients (3 men, 1 woman) age 54 to 77 years were found to have polypoid masses in the urinary bladder. In all cases, histologic examination showed biphasic neoplasms with distinct mesenchymal and epithelial components. The morphologic and immunohistochemical characteristics of the tumors varied. One of the cases was remarkable for the presence of liposarcoma, malignant peripheral nerve sheath tumor, and micropapillary urothelial carcinoma. Two of the patients died 2 years after diagnosis, which is consistent with the previously reported aggressive nature of urinary bladder carcinosarcomas. CONCLUSIONS: Carcinosarcomas of the urinary bladder are rare, aggressive malignant neoplasms. To our knowledge, a liposarcomatous component has been reported in only 1 case previously, and components of micropapillary urothelial carcinoma and malignant peripheral nerve sheath tumor have not been reported previously in carcinosarcomas of the urinary bladder. Because of the aggressive biologic behavior of these tumors, they should be identified promptly and treated appropriately.     

Ovarian tumors of borderline malignancy (tumors of low malignant potential): a critical appraisal.

Before the designations borderline malignancy and low malignant potential were used, the surface epithelial-stromal tumors of the ovary were simply classified into benign and malignant categories. The introduction of the borderline category of tumors has been a great advancement in classification, because it has set apart from the general group of surface epithelial cancers a subgroup with a much better prognosis, stage-for-stage, than that of conventional ovarian carcinomas. Over the last 20 years, pathologists have learned to recognize the distinctive clinicopathologic features of serous borderline tumors as well as the adverse prognostic significance of the associated invasive peritoneal lesions, whether they may represent true implants or independent primary tumors. We have urged our surgical colleagues to search for the peritoneal lesions, and sample them meticulously, and advised our fellow oncologists not to administer adjuvant therapy to patients with noninvasive implants lacking malignant epithelial cells. There is now convincing evidence in the literature that the only fatal cases of serous borderline tumors are those associated with invasive implants, and chemotherapy is indicated only for these rare tumors. It has also been demonstrated that Stage I intestinal mucinous borderline tumors and noninvasive well-differentiated mucinous carcinomas both have an almost equally good prognosis. The current treatment for pseudomyxoma peritonei is still unsatisfactory, but we have recently learned that most of the mucinous ovarian tumors associated with pseudomyxoma peritonei are secondary to similar tumors of the appendix. In the remaining cases, however, the ovarian tumor appears to be responsible for the pseudomyxoma peritonei. Borderline tumors also exist in the endometrioid, clear cell, and Brenner surface epithelial categories, but these tumors have been too rare for clear delineation of their clinical and pathologic features. Recently, some investigators have proposed to abandon the borderline category and to return to the old benign-malignant classification system by dividing unevenly the borderline tumors into a larger group of atypical proliferative epithelial cystadenomas and a smaller category of recently described but still not well-characterized noninvasive carcinomas. In the author's opinion, such a recommendation is misleading because it ignores the possibility of rare but significant behavioral exceptions on each of these two groups of tumors. Furthermore, careful tumor staging is mandatory in both instances regardless of the type of terminology used. It is hoped that by keeping the borderline designation, knowledge on this group of ovarian tumors will continue to expand as it has been until now.     

23-year-old man with a superficial cortical brain tumor

A 23-year-old male presented with a tonic-clonic generalized seizure. Neuroradiological examination revealed a superficial cystic mass with a mural nodule in the right fronto-parietal lobe. Histological and immunohistochemical examination were consistent with a pigmented (melanin producing) desmoplastic ganglioglioma.These tumors have been first described in childhood, one of them displaying melanin deposits. Only twenty cases of non-infantile desmoplastic gangliogliomas have been reported in the literature, none of them pigmented. According to the clinical and histomorphology (including the desmoplastic component) features, the differential diagnosis should include the ganglioglioma, the xanthoastrocytoma pleomorphic (both tumors also with pigmented forms) and the superficial desmoplastic infantile astrocytoma.     

Stromal osteoclast-like giant cells in an adenosquamous carcinoma of the gallbladder.

We report a case an adenosquamous carcinoma of the gallbladder that extended to the proximal transverse colon. Metastatic tumor was present in regional lymph nodes and the liver. Microscopically, the tumor was composed of malignant epithelial cells that were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-positive. The adjacent desmoplastic stroma of the primary tumor, as well as the metastasis, contained giant cells that morphologically resembled osteoclasts. Immunohistochemical studies showed that the giant cells were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-negative but weakly alpha 1-antichymotrypsin-positive. While tumors containing osteoclast-like giant cells have been described in the breast, lung, liver, and thyroid, this is the first report of a tumor with this morphology originating in the gallbladder. The presence of the giant cells adjacent to both the primary and metastatic tumor and not at any other location suggests that the tumor cells are producing a substance that induces the formation of the nontumoral giant cells.