Mixed ovarian large cell neuroendocrine carcinoma, mucinous adenocarcinoma, and teratoma: A report of two cases and review of the literature

Large cell neuroendocrine carcinoma of the ovary is a rare recently established entity. Few cases have been reported in the literature, and they are usually associated with another type of surface epithelial tumor. The association of a large cell neuroendocrine carcinoma with a surface epithelial tumor and a teratoma is even rarer, with only two cases previously described. We report the cases of two patients in their fifties who presented with a growing abdominal mass and died of metastatic disease within less than a year. Histological assessment revealed large cell neuroendocrine carcinoma admixed with mucinous adenocarcinoma and teratoma. Different hypotheses regarding the origin of large cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the composite epithelial tumors originated from the pre-existing teratoma.     

Synchronous chromophobe and papillary renal cell carcinoma. First report and review of the pathogenesis theories

The coexistence of different subtypes of renal cell carcinoma (RCC) within a single kidney is an extremely unusual entity. Presented herein is the case of a 57-year-old man with two RCC of chromophobe and papillary histology. Very few reports in the literature describe double or triple synchronous renal neoplasms. To our knowledge this is the first report of this RCC subtype combination, which might trigger further investigation on the RCC pathogenesis theories.     

Anaplastic spindle cell carcinoma, arising in a background of an ovarian mucinous cystic tumor: a case report with clinical follow up, review of the literature

Anaplastic carcinoma (AC) of spindle cell type is an exceedingly rare ovarian malignant neoplasm. The histo-genesis of these tumors is still controversial. Although it was first thought to carry an invariably unfavorable prognosis, recent data indicates that this does not apply to stage Ia tumors. To date, there have been less than ten cases of anaplastic spindle cell carcinoma reported in the medical literature. Furthermore, our case is the first time this tumor has been described in a 40-year-old female with malignant spindle cells merging with conventional high grade adeno-carcinoma. The differential diagnosis of spindle cell proliferation in the ovary will be discussed and their distinction using a panel of immunohistochemical stains. This report demonstrated that the findings of malignant spindle cell proliferation does not imply this entity to be carcinosarcoma. The distinction of AC from true sarcomas is important because of the poorer prognosis of the later compared with the quite favorable behavior of AC. However, such existence necessitates a careful tissue sampling for the logical distinction between AC and carcinosarcoma, which is critical for planning further management and ultimately the predictor of prognosis.     

Small cell carcinoma of the ovary: An immunohistochemical and ultrastructural study with a review of the literature

Summary This is an immunohistochemical and ultrastructural study of two small cell carcinomas of the ovary with a review of the literature. These cases showed a dimorphic population of small and large cells sharply demarcated from each other. Cytokeratin 18 and vimentin were mainly expressed in the large tumour cells, some of which also stained for alpha-smooth muscle actin. Periodic-acid-Schiff-positive, alpha-1-antitrypsin-positive hyaline globules were present in one case. Ultrastructural findings included filamentous nucleolonema as well as evidence of smooth muscle differentiation. Some of these observations have not been previously reported. Certain of the above features seem to support a germ cell origin of small cell carcinoma, but they cannot be considered specific for germ cell neoplasms. Thus, small cell carcinoma of the ovary cannot be classified into one of the known categories of ovarian tumours at the present time.     

Morphological and molecular basis of ovarian serous carcinoma

Serous carcinoma is the most common type of epithelial ovarian cancer. In this review, we provide a comprehensive picture of ovarian serous cancers from multiple aspects: the first part of this review summarizes the morphological, histological, and immunological signatures of ovarian serous carcinoma; subsequently, we review the history of the evolvement of different grading systems used in ovarian serous cancer; in the end, we focus on characterizing the genetics that underlie the 2-tiered pathways through which ovarian serous cancers are believed to arise: the low-grade and the high-grade pathways.     

Pathological staging of renal cell carcinoma: a review of 300 consecutive cases with emphasis on retrograde venous invasion

Aims

Pathological staging of renal cell carcinoma (RCC) can be challenging compared to other cancer types, as invasion often manifests as finger‐like protrusions into vascular spaces or renal sinus tissue. Although prior studies have shown larger tumour size to be correlated highly with renal sinus invasion, prospective data on evaluating pathological stage are limited. We evaluated a large series reported by one urological pathologist.

Methods and results

Three hundred consecutive specimens were reviewed. Tumours larger than 5 cm were routinely sampled extensively or grossly re‐reviewed when no extrarenal extension was identified on initial examination. Apparent multifocal disease was assessed critically for intravascular spread. Retrograde venous invasion was reported in 15 of 300 (5%) cases, 13 of 15 of which were clear cell RCC. Of a total of 163 specimens with clear cell histology, only five of 34 (15%) tumours 7 cm or larger were reported as pT2, all of which had an explanatory comment indicating the absence of definitive extrarenal spread. In contrast, 15 of 20 (75%) pT2 tumours were non‐clear cell histology (papillary, chromophobe and translocation‐associated). Comparing pT3a or higher tumours, the median tumour size in cases with retrograde venous invasion was 8.0 cm, compared to 6.2 cm in cases without retrograde venous invasion (P = 0.005).

Conclusions

Our findings support that retrograde venous invasion should be considered carefully before diagnosing multifocal clear cell RCC, which is rare in the sporadic setting. In the absence of vascular invasion, multifocal clear cell papillary RCC can be a mimic. pT2 occurs more frequently with non‐clear cell histology (particularly papillary or chromophobe RCC).

     

Immunohistochemical biomarkers of value in distinguishing primary ovarian carcinoma from gastric carcinoma: a systematic review with statistical meta-analysis

Aims:  To compare the relative risk of antigen expression being detected immunohistochemically in ovarian and gastric carcinoma aggregated from studies performed for diagnostic purposes, with the relative risks of their expression in all patients in the English literature.
Methods and results:  Both types of series indicated that cytokeratin (CK) 7 expression was greater and that of CK20 and carcinoembryonic antigen less in ovarian than in gastric carcinoma ( P  < 0.05). Synthesis of all data available for MUC-2 suggested it was more commonly expressed in ovarian carcinoma, whereas the relative risk in papers that directly compared its expression suggested that it was more common in the gastric carcinoma ( P  = 0.2, NS). Aggregating all possible data suggested villin was more likely to be expressed in ovarian cancers, whereas studies in which its expression was compared directly in both tumours suggested the opposite. Although statistically significant, patient numbers were small.
Conclusion:  Provided sufficient numbers of cases are studied, analysis of studies comparing antigen expression for diagnostic purposes in tumours from two body sites is likely to be supported in the wider literature. The design of such comparative studies is informed by aggregating data from single tumour studies.     

Ovarian spindle cell lesions: a review with emphasis on recent developments and differential diagnosis

Ovarian lesions composed of spindle cells comprise a heterogeneous group; most are neoplastic but several non-neoplastic conditions are also composed of spindle cells. This review discusses the main differential diagnoses of an ovarian spindle cell lesion, especially concentrating on the recent literature. The majority of ovarian spindle cell lesions fall into the broad category of fibromatous neoplasms whereas others in the sex cord-stromal group may also be composed of spindle cells, including thecomas, granulosa, and Sertoli-Leydig cell tumors and rarer neoplasms, such as sclerosing stromal tumor and signet-ring stromal tumor. In the recent past there have been several major contributions on various aspects of ovarian spindle cell lesions, including cellular and mitotically active cellular fibromatous lesions, smooth muscle neoplasms, and metastatic gastrointestinal stromal tumors. Other mesenchymal or epithelial tumors and mixed epithelial and mesenchymal neoplasms may also enter into the differential diagnosis of an ovarian spindle cell lesion. Several non-neoplastic lesions may be composed of spindle cells, including massive edema, ovarian fibromatosis, stromal hyperplasia, and stromal hyperthecosis. Morphology remains the mainstay in diagnosis but immunohistochemistry may be invaluable in certain circumstances, one example being the identification of a metastatic gastrointestinal stromal tumor within the ovary.     

Mature ovarian cystic teratoma with combined squamous cell carcinoma and malignant melanoma

 In a mature ovarian cystic teratoma (MOCT) in a 67-year-old woman we found associated invasive squamous cell carcinoma and nodular amelanotic malignant melanoma. The finding of foci of typical and atypical melanocytic proliferation at the junctional level of the dermal component together with the absence of other possible sources supports an ovarian origin of the melanoma. A comparative analysis of the reported MOCT-associated malignant melanomas emphasizes the singularity of our case in the amelanotic character of the melanoma, its lymphotropism and the coexistence of invasive squamous cell carcinoma. Received: 23 October 1997 / Accepted: 30 December 1997     

Synchronous double cancers of colonic large cell neuroendocrine carcinoma and gastric squamous-cell carcinoma: a case report and review of literature

Either colonic large cell neuroendocrine carcinoma (LCNEC) or gastric squamous-cell carcinoma (SCC) is extremely rare, with a very poor prognosis due to the high rate of distant metastases. Here, we report the first case of synchronous double malignancies in form of colonic LCNEC and gastric SCC. A 66-year male underwent a right hemicolectomy for a mass obstructing the ascending colon and an emergent gastroscopic hemostasis for another hemorrhagic stomach mass. Histopathological examination confirmed colonic LCNEC displaying the characteristic of large, vesicular nuclei with variable amounts of cytoplasm and gastroscopic biopsy revealed poorly-differentiated gastric SCC. Immunohistochemical staining of LCNEC demonstrated positive activities for chromogranin A, synaptophysin, CD56, NSE, ki-67 (>95%), but negative for CD99, CK20 and TTF-1. The patient had suffered from an accelerated growth of multiple liver metastases after surgery, suggestive of concomitant tumor resistance (CR), and survived 2 months after discharge.     

Endometrioid carcinoma with a low-grade spindle cell component: a tumor resembling an adnexal tumor of probable Wolffian origin

Endometrioid carcinoma is known to have many histopathologic variants, which may cause diagnostic difficulty. One rare variant resembles Wolffian adnexal tumor (female adnexal tumor of probable Wolffian origin). This pattern can produce a significant solid component within the tumor. Once the true endometrioid nature of the tumor is recognized, the tumor can appear deceptively high grade by International Federation of Gynecology and Obstetrics grading criteria, which take into account the percentage of the tumor showing solid growth. The English-language literature on this variant is scant, and its behavior is not well documented. We present a case of ovarian endometrioid carcinoma with a Wolffian adnexal tumor pattern that recurred 19 years after the original surgery; and the patient continues to remain well without evidence of disease 1 year following her second surgery, that is, 20 years of indolent behavior. This long clinical course shows evidence for low-grade behavior for this tumor.     

Fine-needle aspiration cytology of medullary breast carcinoma: report of two cases and review of the literature with emphasis on differential diagnosis

Medullary carcinoma is a rare variant of breast carcinoma with a relatively good clinical prognosis as strictly defined. Characteristic features on fine-needle aspiration cytology (FNAC) allow medullary carcinoma to be considered in the cytologic differential diagnosis. We present two FNAC cases with such features, including high cellularity with clusters and single intact malignant cells, bizarre stripped nuclei with prominent nucleoli in a lymphoplasmacytic background, and illustrate one case in liquid-based preparation. Surgical excision revealed that one patient had medullary carcinoma, while the second patient had high-grade infiltrating ductal carcinoma. Breast FNAC samples with syncytial fragments, bizarre nuclei with prominent nucleoli, and a chronic inflammatory infiltrate should raise the possibility of medullary carcinoma. However, the differential diagnosis also includes high-grade ductal carcinoma, lymphoma, or metastasis to breast or intramammary lymph nodes; thus, histopathologic analysis is required for definitive diagnosis.     

Dishevelled family proteins in serous ovarian carcinomas: a clinicopathologic and molecular study

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non-canonical Wnt signaling that are important for embryonic development. Since Wnt signaling promotes cell proliferation and invasion, its increased activation is associated with cancer development as well. To get deeper insight into the behavior of Dishevelled proteins in cancer, we studied their expression in serous ovarian carcinomas [both low- (LGSC) and high-grade (HGSC)], and HGSC cell lines OVCAR5, OVCAR8, and OVSAHO. DVL protein expression in serous ovarian carcinomas tissues was analyzed using immunohistochemistry, while DVL protein and mRNA expressions in HGSC cell lines were analyzed using Western blot and quantitative real-time PCR. DVL1 protein expression was significantly higher in LGSC compared with normal ovarian tissue, while DVL3 was overexpressed in both LGSC and HGSC. DVL2 and DVL3 protein expression was higher in HGSC cell lines when compared with normal control cell line FNE1, while DVL1, DVL2, and DVL3 mRNA expression was significantly increased only in OVSAHO cell line. Survival analysis revealed no significant impact of DVL proteins on patients’ outcome. Our data show an active involvement of Dishevelled family proteins in serous ovarian carcinomas. Further studies should confirm the clinical relevance of these observations.     

Merkel cell carcinoma: a review and update on current concepts

Merkel cell carcinoma (MCC) is a malignant, cutaneous neuroendocrine tumour of the elderly with an increasing worldwide incidence. Clinical presentation is generally characterized by a rapidly-evolving dermal tumour on sun-exposed skin of the head, neck or extremities. Histologically, there are sheets and cords of uniform, small cells with hyperchromatic nuclei and multiple small nucleoli. Mitoses and apoptotic bodies are widespread and lymphovascular involvement is commonly present. Aggressive surgical treatment of localized primary lesions followed by radiotherapy remains the mainstay of treatment. Lymph node metastases, local recurrences, and widespread dissemination are commonly seen. The 10-year survival rates for MCC are 71%, 48%, and 20% for localized, regional, and distant disease, respectively. Merkel cell polyomavirus (MCV) has been implicated as a contributing factor in the pathogenesis of MCC with approximately 80% of tumours showing positivity for the virus. This review provides an up-to-date overview of the clinicopathologic features, current knowledge of MCV, and recent advances in diagnosis, prognostication, and management of MCC.     

Undifferentiated carcinoma of the endometrium: a review

Undifferentiated carcinoma of the endometrium is a high grade carcinoma and under-recognised, frequently diagnosed as grade 3 endometrioid carcinoma. We have found that undifferentiated carcinoma represents 9% of all endometrial carcinomas; it is composed of solid sheets of epithelial cells and in most cases only 5-10% of the cells are positive for keratin. The recognition of undifferentiated carcinoma is extremely important when this neoplasm is associated with a grade 1 or grade 2 endometrioid adenocarcinoma. In this situation it is important to diagnose the solid areas of carcinoma as undifferentiated and avoid evaluating them as the solid component of endometrioid carcinoma because there is significant difference between the excellent prognosis of grade 2 endometrioid carcinoma, the intermediate prognosis of grade 3 carcinoma, and the poor prognosis of undifferentiated carcinoma, which in cases of association with differentiated areas should be diagnosed as dedifferentiated endometrioid carcinoma.     

以卵巢囊肿为首发症状的肺小细胞癌1例并文献复习

目的:探讨l例以卵巢囊肿为首发症状的肺小细胞癌患者的临床病理特征.方法:对该患者的临床表现、病理特征及免疫组织化学表型进行观察、分析,并做相关文献复习.结果:该患者首发症状为卵巢囊肿,囊壁附一灰白结节,镜下为小细胞癌形态,术后结合临床表现及免疫组化表型结果,诊断为肺小细胞癌转移至卵巢子宫内膜异位囊肿.结论:肺小细胞癌转移至卵巢子宫内膜异位囊肿是一种极罕见的现象,其确诊依赖于临床资料及组织病理学检查.