Ovarian neoplasms composed of small round cells: a review

Ovarian neoplasms composed predominantly or exclusively of small round cells with scant cytoplasm are relatively rare. However, there is a wide differential, and pathologists often struggle to make a correct diagnosis because of overlapping histologic features. Perhaps the best known of these neoplasms is ovarian small cell carcinoma of hypercalcemic type (OSCCHT), a tumor of unknown histogenesis. This may be confused with a wide range of neoplasms ranging from sex cord-stromal tumors (some of which may exhibit a small cell phenotype) to neoplasms in the family of small round blue cell tumors to various undifferentiated malignancies. A neuroendocrine small cell carcinoma, so-called small cell carcinoma of pulmonary type, may also arise within the ovary, and this may be a component of a typical ovarian surface epithelial-stromal tumor. In addition to the well-known family of small round blue cell tumors of childhood, other small cell neoplasms that may arise within the ovary or involve the ovary include intra-abdominal desmoplastic small round cell tumor, metastatic small cell carcinoma, peripheral and central primitive neuroectodermal tumor, and endometrial stromal sarcoma. Malignant melanoma, undifferentiated carcinoma, and various germ cell tumors, especially dysgerminoma and immature teratoma, also on occasion enter into the differential diagnosis of an ovarian small cell neoplasm. In this review, the morphologic features of some of these neoplasms are described, as is the value of immunohistochemistry and other ancillary techniques in establishing a diagnosis.     

Primary desmoplastic small round cell tumor of bone: report of a case with cytogenetic confirmation

We report a case of desmoplastic small round cell tumor occurring in the right ilium of a 13-year-old boy. Morphologically, the neoplasm consisted of small round cells of primitive appearance with a diffuse growth pattern replacing marrow space and eroding bone. Immunohistochemical staining was positive for vimentin, synapsin, CD99 (MIC2 protein), and FLI-1, prompting an initial diagnosis of Ewing sarcoma/primitive neuroectodermal tumor. However, a diagnosis of desmoplastic small round cell tumor was rendered after the detection by cytogenetic analysis of the reciprocal chromosomal translocation, t(11;22)(p13;q12), which is uniquely associated with this tumor. This is the first documented instance of desmoplastic small round cell tumor arising in bone.     

Desmoplastic small round cell tumors: cytologic, histologic, and immunohistochemical features

Desmoplastic small round cell tumor (DSRCT) is a recently recognized clinicopathologic entity that has a predilection for adolescent males and usually affects the abdominal cavity. Due to its uncommon nature, many pathologists lack experience with this tumor. The literature regarding DSRCT is reviewed with special attention to its histologic and cytologic diagnosis. Morphologic features of DSRCT and its immunohistochemical and cytogenetic profile are summarized and differential diagnosis with other small round cell tumors is discussed. As observed by both histologic and cytologic examinations, small round blue cells and fibrosclerotic stroma are the striking morphologic features of DSRCT. The typical immunohistochemical profile is characterized by coexpression of epithelial, mesenchymal, myogenic, and neural markers. Cytogenetically, this tumor harbors a specific karyotypic abnormality, namely t(11;22)(p13;q12). These features distinguish DSRCT from other members of the family of small round cell tumors.     

Electron microscopy and other ancillary techniques in the diagnosis of small round cell tumors

The current study disusses a new approach to the group of small round cell tumors (SRCTs) independently of their primary anatomical location. We perform this analysis supported mainly by morphological means and particularly with the help of immunohistochemistry and electron microscopy; the last of which continues to play a decisive role in their differential diagnosis. The microscopical similarity of many of these tumors often makes the diagnosis in routine histology extremely difficult, due to the varying degree of heterogeneity present, and may have important therapeutic and prognostic implications. Thus a correct final diagnosis is mandatory for the clinic. Within the group of tumors that express a dominant or occasional small round cell pattern "SRCT" (neoplasms of the Central Nervous System excluded) are included: Ewing's sarcoma and peripheral neuroectodermal tumor (Es/pPNET) comprising its varieties, neuroblastoma, desmoplastic small round cell tumor, rhabdomyosarcoma, alveolar, solid and embryonal, small cell osteosarcoma, chondrosarcoma, myxoid and mesenchymal, round cell and myxoid liposarcoma, synovial sarcoma (monophasic undiffentiated), primitive malignant peripheral nerve sheath tumor (malignant small cell schwannoma), malignant non-Hogdkin lymphoma, Merkel cell tumor of the skin (small cell carcinoma including neuroendocrine carcinoma). This study discusses in each case not only the histology, supported by immunohistochemistry, but also the main ultrastructural characteristics. We are conscious that in some cases further cytogenetic or molecular biology support may be necessary, when considering the limits of morphology today. Thus, short references on molecular genetics, complementing the structural findings, are given.     

NKX3.1 a useful marker for mesenchymal chondrosarcoma: An immunohistochemical study

IntroductionMesenchymal chondrosarcoma is a rare subtype of chondrosarcoma. The tumor has a characteristic bimorphic pattern with areas of poorly differentiated small round cell component and interspersed islands of well differentiated hyaline cartilage. Histological diagnosis of mesenchymal chondrosarcoma is very challenging especially in small biopsies when tumor presents with little cartilaginous component. In such cases, it is very difficult to distinguish mesenchymal chondrosarcoma from other round blue cell tumors like Ewing's sarcoma, rhabdomyosarcoma, small cell osteosarcoma and desmoplastic round blue cell tumor. Immunohistochemically, mesenchymal chondrosarcoma stains positive for NKX2.2, CD99, S100 and SOX9. This immunoprofile is non-specific and overlaps with other round blue cell tumors. Till recently, there was no reliable immunohistochemical marker to differentiate mesenchymal chondrosarcoma from other round blue cell tumors.NKX3.1, though widely used as a diagnostic biomarker for prostatic adenocarcinoma, has been recently proposed by Yoshida et al. (2020) as a unique marker of mesenchymal chondrosarcoma and EWSR1-NFATC2 sarcoma.ObjectiveThe aim of our study was to further explore utility of NKX3.1 as a diagnostic marker of mesenchymal chondrosarcoma.Material & methodsWe applied NKX3.1 immunohistochemistry to 21 cases of mesenchymal chondrosarcoma and 32 cases of other round blue cell tumors.Results14 out of 21 cases (66.7%) of mesenchymal chondrosarcoma stained positive for NKX3.1 with nuclear expression in small round component. Cartilaginous component was predominantly negative. All other round blue cell tumors showed negative results.ConclusionBased on our study results we suggest that NKX3.1 is a useful immunohistochemical marker in differentiating mesenchymal chondrosarcoma from its histological mimics.     

卵巢幼年型粒层细胞瘤8例临床病理分析

目的 探讨卵巢幼年型粒层细胞瘤(juvenile granulosa cell tumor, JGCT)的临床病理特点、诊断及鉴别诊断.方法 回顾本院诊治的8例JGCT的临床、病理特征及免疫表型特点,并进行随访获知其预后情况.结果 8例JGCT患者发病年龄6～21岁,平均15.1岁.临床主要表现为腹部包块、腹水及女性假性性早熟.巨检表现为囊实性肿块.光镜下肿瘤细胞呈实性巢状,片状弥漫性排列,部分可排列成多个圆形或椭圆形大小不等的滤泡,少数可形成巨滤泡结构,有的滤泡腔内还可见均质红染物质.瘤细胞呈圆形、多边形,中等大小或较大,胞质丰富,空淡或微嗜酸性,核圆形,染色质均质状,无明显核沟,有一定异型性,可见核分裂象.免疫表型:瘤细胞均表达inhibin-α、CD99、vimentin,部分病例Melan-A、calretinin、S-100阳性,瘤细胞不表达CKpan、EMA、PLAP、Syn和CgA.结论 JGCT非常少见,属于低度恶性肿瘤,预后较好.确诊依赖于临床特点、组织形态学及免疫组化标记.病理诊断时要与卵巢的成人型粒层细胞瘤、高钙血症型小细胞癌、类癌、无性细胞瘤等肿瘤相鉴别.     

Metastatic retinoblastoma presenting as a left shoulder soft tissue mass: FNA findings and review of the literature

Retinoblastoma is a relatively rare malignant pediatric tumor accounting for ～3% of childhood cancers and 1% of all cancer deaths in children under 15 years of age. During the clinical course of the disease, a metastasis usually occurs within the first year of diagnosis and is seen in 2% of retinoblastoma patients. Metastases to the intracranial region are common and account for ～50% of the metastatic cases. Metastasis to the soft tissue is very rare. Herein, we report a case of metastatic retinoblastoma presenting as a left shoulder soft tissue mass in a 14‐year‐old female with a 14‐year history of familial bilateral retinoblastoma status post radiation therapy. In our case, the FNA cytology shows some features of the small round blue cell tumor group with inconspicuous Flexner‐Wintersteiner or Homer‐Right rosette formation. The unusual clinical presentation and morphology give rise to a diagnostic dilemma, with the differential diagnosis centering on the small round blue cell tumors such as lymphoma, rhabdomyosarcoma, nephroblastoma (Wilms' tumor), Ewing's sarcoma/PNET, and desmoplastic small round cell tumor. It also prompts concern for the development of a second primary tumor. The purpose of our study is to discuss the FNA cytology of metastatic retinoblastoma, its differential diagnoses, and the utility of immunohistochemistry. An accurate diagnosis is imperative due to the differences in prognosis and treatment implications for the various diseases. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Alveolar rhabdomyosarcoma of the paranasal sinuses in a 57-year-old woman with 1:16 translocation

Alveolar rhabdomyosarcoma is an uncommon tumor. It is a rare malignancy in adults and rarely occurs in paranasal sinuses in those aged older than 50 years. This report describes a locally invasive and destructive alveolar rhabdomyosarcoma arising in the ethmoid sinus of a 57-year-old woman. The small round blue cell tumors are positive for myogenin by immunohistochemistry and have a karyotype of 45, XX, -5, -13, der(16)t(1;1) (q21;q13) by cytogenetic analysis. Fluorescence in situ hybridization demonstrated a complex translocation with break apart of the FKHR region, which supports a diagnosis of alveolar rhabdomyosarcoma. This report characterizes this tumor through microscopic and cyto-genetic analysis and emphasizes the importance of considering rhabdomyosarcoma in the differential diagnosis of small round cell tumors of the head and neck region in the middle-aged adults.     

From conventional fluid cytology to unusual histological diagnosis: Report of four cases

Malignant small round cell tumors represent a diagnostic challenge for cytologists and pathologists. This case series describes four cases of unusual metastasis of small round cell tumors subtypes into body cavities generating effusions in which fluid cytological examination suggested the neuroendocrine origin of the tumors. Tumor diagnosis (Ewing sarcoma/primitive neuroectodermal tumor and desmoplastic small round cell tumors) were unknown at the cytological evaluation. We can highlight the importance of the accurate analyses of body fluids, both for early diagnosis of metastatic disease, and for the diagnosis of primary tumor when serous effusion is the first manifestation of the neoplasia. Diagn. Cytopathol. 2013;41:348–353. © 2011 Wiley Periodicals, Inc.     

Imprint cytology of high-grade immature ovarian teratoma: a case report, literature review, and distinction from other ovarian small round cell tumors

Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm characterized by immature neural tissue. The cytomorphologic features have only rarely been described. We herein describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with imprint cytology. A 35-year-old woman presented with a pelvic mass which was resected and sent for frozen section evaluation. Imprint smears and frozen section of the mass were diagnostic of IOT. IOT has diagnostic cytologic features which show complete concordance with histology. Differential diagnoses include other small round cell neoplasms such as ovarian neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and Non-Hodgkin lymphoma. Distinguishing IOT from these tumors can be challenging however if diligent morphologic study and/or ancillary studies are performed accurate diagnosis is possible.     

骨外Ewing肉瘤/外周原始神经外胚叶肿瘤的临床病理分析

目的探讨骨外Ewing肉瘤／外周原始神经外胚叶肿瘤的临床病理特征及诊断、鉴别诊断依据。方法18例骨外Ewing肉瘤／外周原始神经外胚叶肿瘤行常规病理检查及免疫组化染色,其中2例进行电镜检查。结果光镜显示肿瘤组织主要由小圆形或卵圆形细胞组成,免疫组化染色显示肿瘤细胞膜CD99强阳性,电镜显示肿瘤细胞质内有神经内分泌颗粒。结论骨外Ewing肉瘤/外周原始神经外胚叶肿瘤的诊断依赖病理特征,并需要与其他小细胞恶性肿瘤进行鉴别。     

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.     

Epithelial marker-negative desmoplastic small round cell tumor with atypical morphology: definitive classification by fluorescence in situ hybridization

Desmoplastic small round cell tumor typically presents with abundant desmoplastic stroma containing nested primitive round cells bearing a polyphenotypic immunohistochemical profile. Lesions with minimal classic morphology pose a formidable diagnostic challenge. The current case represents one such example, arising as a large abdominal-pelvic mass in a 17-year-old female patient. The tumor was composed of a monomorphous population of small round cells lining microcystic structures and forming pseudoacini and fine anastomosing trabeculae and cords. The stroma was abundantly myxoid with only occasional thick desmoplastic septa. The tumor cells were variably immunopositive for vimentin, desmin, smooth muscle actin, synaptophysin, neuron-specific enolase, Bcl-2 and WT1 (nuclear); epithelial markers were negative. The definitive diagnosis of desmoplastic small round cell tumor was rendered with the demonstration of the characteristic EWS-WT1 gene fusion by fluorescence in situ hybridization. The current case emphasizes the utility of fluorescence in situ hybridization to demonstrate EWS-WT1 gene fusion in desmoplastic small round cell tumor with nonclassic morphologic and immunohistochemical features to avoid potential misdiagnosis.     

Intraabdominal desmoplastic small round cell tumor: Cytopathologic findings in two cases

Intraabdominal desmoplastic small round cell tumor (DSRCT) is an extremely rare entity. This study describes fine-needle aspiration, ascitic fluid, and touch imprint cytomorphology of DSRCT in 2 patients with extensive abdomino-pelvic disease. Cytopathologic features were unique and showed good morphologic correlation with subsequent histology of the resected tumor. Immunocytochemical profile and differential diagnosis with other small round cell tumors in this age group are also discussed. Diagn. Cytopathol. 1998;18:449–452. © 1998 Wiley-Liss, Inc.     

Malignant small round cell tumor of the heart: a diagnostic dilemma.

We report a rare malignant small round cell tumor of the heart in a 26-year-old woman. She had been symptomatic 15 days after vaginal delivery. Immunohistochemistry revealed divergent differentiation; hence, the tumor was designated as desmoplastic small round cell tumor. This is the first report of such a tumor in the heart.     

Desmoplastic small round cell tumor with sphere‐like clusters mimicking adenocarcinoma

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere‐like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients. Diagn. Cytopathol. 2015;43:214–217. © 2014 Wiley Periodicals, Inc.