Neuroendocrine carcinomas (carcinoid tumor) of the testis. A clinicopathologic and immunohistochemical study of ten cases

We studied 10 cases of primary pure testicular neuroendocrine carcinoma. Patients were between 16 and 48 years old and had testicular swelling with pain or a painless testicular mass and no history of neuroendocrine carcinoma or other malignant neoplasm. All underwent orchiectomy. The tumors were low (n = 9) and intermediate (n = 1) grades with a variegated histologic appearance characterized by a nesting pattern, cords of neoplastic cells with rosettes, or sheets of neoplastic cells. Mitotic activity was lacking in 9 cases. In 1 case, mitotic figures ranged from 7 to 8 per 10 high-power fields, and cellular atypia and comedo-like necrosis were present. Immunohistochemical studies using a keratin cocktail, chromogranin, synaptophysin, epidermal growth factor, p53, placental-like alkaline phosphatase, and CD117 (c-kit) were performed in all cases. Keratin, chromogranin, and synaptophysin were positive in all tumors. Clinical follow-up information was obtained for 6 patients (range, 12-60 months): 5 with low-grade tumors were alive 24 to 60 months after diagnosis; 1 with an intermediate-grade tumor died of tumor 12 months after initial diagnosis. The behavior of these tumors, while in the testicular region, correlates well with the histologic grade. We propose replacing the term testicular carcinoid with neuroendocrine carcinoma, which better reflects the nature of these neoplasms.     

Spindle-cell neuroendocrine carcinomas of the thymus (spindle-cell thymic carcinoid): a clinicopathologic and immunohistochemical study of seven cases.

Seven cases of spindle-cell neuroendocrine carcinomas (carcinoid tumors) of the thymus are presented. The patients were three women and four men between the ages of 26 and 74 years (median age, 50 yr). The lesions presented as large anterior mediastinal masses on radiographic examination and were treated by surgical excision. Grossly, the tumors were tan-brown and well circumscribed but encapsulated, and they measured from 2 to 15 cm in greatest diameter. Histologically, they were characterized by a dense proliferation of spindle cells that focally adopted a vaguely organoid pattern, with discrete nests of tumor cells separated by thin fibrovascular septa. Mitotic figures were present in all of our cases and ranged from 2 to 8 per 10 high power fields. Focal areas of necrosis were also present in all of the cases. Immunohistochemical studies performed in six cases showed positive staining for chromogranin in five cases, synaptophysin and keratin in four, and Leu 7 in three. Clinical follow-up showed that two patients died of their tumors 6 and 11 years after diagnosis; one was alive 8 years after diagnosis. Spindle-cell neuroendocrine carcinomas of the thymus (spindle-cell thymic carcinoids) should be considered in the differential diagnosis of spindle-cell neoplasms of the anterior mediastinum. Because of their aggressive clinical behavior, it is important to separate them from the other benign or low-grade spindle-cell tumors that are more common at this location.     

Primary neuroendocrine carcinoma (thymic carcinoid) of the thymus with prominent oncocytic features: a clinicopathologic study of 22 cases.

Twenty-two cases of oncocytic thymic neuroendocrine carcinomas (carcinoid tumors) are presented. The patients were 17 men and 5 women between the ages of 26 and 84 years (median, 55 years). Nine were asymptomatic, and the tumor was found on routine examination; four patients presented with chest pain, two with weight loss, two with multiple endocrine neoplasia I syndrome, and one with Cushing's syndrome. Surgical resection of the mediastinal tumor was performed in all cases. The lesions were described as soft, light tan to brown, measuring from 3 to 20 cm in greatest diameter. On cut section, the tumors showed a homogeneous surface, soft consistency, and focal areas of hemorrhage. Microscopically, the lesions were characterized by nests or trabeculae of tumor cells that contained abundant granular to densely eosinophilic cytoplasm, with round to oval nuclei and in some areas prominent nucleoli. Mitotic figures ranged from 2 to 10 per 10 high-power fields; foci of comedonecrosis were seen in all cases. Immunohistochemical studies including broad spectrum keratin, CAM 5.2, chromogranin, synaptophysin, Leu-7, and p53 were performed in 12 cases. All of the tumors were strongly positive for CAM 5.2 low-molecular-weight cytokeratin, 11 showed strong positive reaction for Leu-7, 10 for broad-spectrum keratin, 8 for chromogranin, 7 for synaptophysin, and only 1 case showed focal positive staining of the tumor cells for p53. Clinical follow-up of 14 patients showed that 10 were alive between 2 and 11 years, and 4 patients had died of tumor from 4 to 11 years after diagnosis. Patients with good clinical outcome were those whose tumors showed low mitotic activity and minimal nuclear pleomorphism, whereas those who had died of their tumors were those whose tumors were characterized by marked nuclear atypia and higher mitotic rates. Oncocytic thymic carcinoids should be added to the differential diagnosis of anterior mediastinal neoplasms characterized by a monotonous population of tumor cells with prominent oncocytic features.     

Cystic well-differentiated neuroendocrine carcinoma (carcinoid tumor): a clinicopathologic and immunohistochemical study of two cases

Two cases of primary neuroendocrine carcinoma (carcinoid tumor) arising in the walls of a multilocular thymic cyst (MTC) are described. The patients were 2 men, ages 36 and 44 years. Clinically, the patients had chest pain, cough, and dyspnea. Radiographic evaluation demonstrated the presence of anterior mediastinal tumor in both patients, and complete surgical resection of the tumor mass was performed. The tumors measured approximately 6 and 8 cm in greatest dimension and were cystic with solid areas but did not show areas of necrosis or hemorrhage. Histologic examination revealed a cystic tumor with features similar to those previously described for MTCs. In addition, in the walls of the cystic structures, there was cellular proliferation arranged in a nesting growth pattern, similar to the more solid areas of the tumor. The tumor was characterized by a homogenous cellular proliferation with mild cellular atypia and no more than 2 mitotic figures per 10 high-power fields. Immunohistochemically, the tumor cells showed strong positive reactions for keratin and neuroendocrine markers, ie, chromogranin and synaptophysin. Both patients were alive after periods of 12 and 18 months.     

Thymic neuroendocrine carcinomas with combined features ranging from well-differentiated (carcinoid) to small cell carcinoma. A clinicopathologic and immunohistochemical study of 11 cases

We reviewed 11 cases of primary thymic neuroendocrine carcinomas with combined features ranging from well-differentiated to poorly differentiated neuroendocrine carcinoma. For 3 asymptomatic patients, tumors were discovered during routine examination. Presentation in the other patients was as follows: Cushing syndrome, 2 patients; chest pain, 3 patients; superior vena cava syndrome, 1 patient; and hypercalcemia and hypophosphatemia, 1 patient. No clinical data were available for the 11th patient. All tumors were located in the anterior mediastinum and treated by surgical excision. The lesions were large and well-circumscribed with areas of hemorrhage and necrosis. They were characterized by areas showing a proliferation of monotonous, round tumor cells adopting a prominent organoid pattern admixed with areas showing sheets of atypical cells with hyperchromatic nuclei, frequent mitoses, and extensive areas of hemorrhage and necrosis. Immunohistochemical studies performed in 6 cases showed strong CAM 5.2 low-molecular-weight cytokeratin positivity in all cases, chromogranin and synaptophysin positivity in 4, Leu-7 in 3, and focal positivity for p53 in 2. Follow-up information for 9 cases showed that all patients died of their tumors between 1 and 4 years after diagnosis. The present cases highlight the heterogeneity of neuroendocrine neoplasms and reinforce the notion that these tumors form part of a continuous spectrum of differentiation.     

Phyllodes tumor (cystosarcoma phyllodes) of the breast. A clinicopathologic study of 45 cases

The correlation between the histology and biologic behavior of phyllodes tumor was studied in order to establish the histologic criteria of this tumor, particularly its malignant counterpart. A preliminary analysis of five tumors with metastases revealed that a single essential indicator of malignant potential was the presence of a disproportionate overgrowth of the stromal elements at the expense of the ductal element. The presence or absence of such stromal overgrowth in the tumor showed a positive correlation with the degree of stromal atypism and the rate of mitoses. Seventeen out of 45 tumors were determined to be malignant, on the basis of our criteria. The arrangement of the stromal component in malignant phyllodes tumors was usually one of the particular sarcomatous types, with or without the focal areas of one of the specified types of sarcoma. On the other hand, 24 tumors recurred locally but never metastasized, and were preferentially interpreted to be benign phyllodes tumor. Histologically, these tumors had a general architecture resembling that of fibroadenoma but were characterized by high cellularity expressed by the distinct formation of bundles or fascicles of stromal tumor cells. The remaining four tumors seemed to form a borderline phyllodes tumor subset. A follow-up study revealed that, irrespective of the mode of therapy, the outcome of patients with phyllodes tumor was well correlated with the histologic criteria we proposed.     

Neuroendocrine (Merkel cell) carcinomas of the skin: an ultrastructural study of nine cases

Nine neuroendocrine tumors of the skin were examined by light and electron microscopy. The patients (7 males and 2 females) had an average age of 57 years. Seven tumors were located in the head and neck region. Light microscopic examination showed sheets of cells. In 4 cases, a tendency to form small groups of cells was observed. Contact with the epidermis was seen in only 2 cases. The dominant ultrastructural feature was the presence of cytoplasmic processes that contained membrane-bound granules 100-200 nm. Three tumors recurred locally, and in 7 patients, regional nodal metastases occurred. Three patients died of disseminated disease.     

Neuroendocrine carcinoma of the thymus: Aspiration biopsy,immunocytochemistry, and clinicopathologic correlates

We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. in all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear “buttons” found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy. © 1995 Wiley- Liss, Inc.     

胰腺实性-假乳头状瘤8例临床病理分析

目的 探讨胰腺实性-假乳头状瘤(SPT)的临床病理学及免疫组化特点。方法 8例SPT作HE、PAN、免疫组织化学(SP法)染色观察。结果 8例SPT中7例为女性，1例男性，年龄16～63岁，平均33．1岁。术后均无复发。肿瘤体积较大，平均直径7．9cm。有包膜，囊实性相间。镜检：肿瘤由乳头和囊实区混合组成，细胞形态一致，核圆或卵圆，异型不明显，核分裂象罕见。瘤细胞围绕纤维血管轴心形成特征性假乳头结构。2例侵犯胰腺组织。8例Vim、α1-AT、α1-ACT和NSE均阳性，4例Syn、CgA和AE1／AE3阳性，5例CD56阳性，5例PR阳性；Glu、Ins、Pol、EMA、p53、Ki-67、ER均阴性。结论 胰腺SPT好发年轻女性，具有独特的临床病理特点，手术切除治愈率高，应视为低度恶性肿瘤，免疫组化提示可能起源于胰腺多能干细胞。     

Clinicopathologic and DNA cytometric analysis of carcinoid tumors of the thymus.

Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.     

颗粒细胞瘤15例临床病理分析

目的探讨颗粒细胞瘤的组织起源及临床病理学特征。方法回顾分析15例颗粒细胞瘤的临床资料及组织学形态特征,并采用免疫组化(SP法)观察其免疫表型。结果良性颗粒细胞瘤13例,恶性颗粒细胞瘤2例。男性5例,女性10例,年龄19~69岁,平均年龄41·6岁,2例恶性颗粒细胞瘤年龄分别为67岁和69岁。良性颗粒细胞瘤直径0·4~5·3cm,平均2·3cm,2例恶性颗粒细胞瘤直径分别为6和14cm。均为单发病例,临床上主要表现为真皮、皮下或黏膜下孤立性无痛性结节,分别位于腰部3例、腋下、胸壁各2例,乳腺、上臂、子宫、肛周、声带、食管、结肠、舌部各1例。病理组织学上,良性颗粒细胞瘤的肿瘤细胞通常有比较丰富的嗜酸性颗粒状胞质和小而深染的胞核,而恶性颗粒细胞瘤的肿瘤细胞中可见带有明显核仁的空泡状核,细胞核明显异型及部分细胞呈梭形。免疫组化示神经标记物NSE、S-100蛋白强阳性,表达溶菌酶的标记物CD68也强阳性,而表达平滑肌和横纹肌的标记物SMA、MG均阴性。结论颗粒细胞瘤为来源于雪旺细胞的肿瘤,恶性者少见,大多发生在年龄大的患者,且肿瘤体积比较大。     

Juvenile granulosa cell tumor of the ovary: A comprehensive clinicopathologic analysis of 15 cases

ObjectiveJuvenile granulosa cell tumor(JGCT) is an uncommon ovarian sex-cord stromal tumor, with diverse clinical, radiological and histopathologic features. The present study describes the clinicopathological and histomorphological spectrum of JGCTs, and highlights the key differentiating features from its mimics.MethodsA retrospective analysis of all cases reported as JGCTs during 2011–19 (8 years) was performed with detailed evaluation of clinical, histopathologic data and follow-up details.ResultsOf a total 115 GCTs reported during the study period, 15(13%) were reported as JGCTs. The mean age at presentation was 17 years. Abdominal pain and distension were the most common clinical presentations. Five patients were pre-menarchal with 3 exhibiting precocious puberty. Majority of tumors were unilateral(left>right), solid-cystic, ranging in size from 4 to 20 cm. Microscopically, macrofollicular architecture was most frequent (n = 12;80%). The tumor cells depicted variable nuclear pleomorphism, small distinct nucleoli and moderate-abundant pale eosinophilic-clear/vacuolated cytoplasm. Mitotic activity ranged from 1 to 10/10HPFs. Uncommon histopathologic features included microcystic and tubulo-cystic architecture, myxoid degeneration, bizarre tumor giant cells, hob-nailing of the tumor cells, intracytoplasmic hyaline globules, multifocal calcification and thick hyalinized blood vessels. Majority(n = 12;80%) presented in stage I. Surgical treatment included unilateral salpingo-oophorectomy without any adjuvant chemotherapy, bilateral salpingo-oophorectomy (BSO) and total abdominal hysterectomy with BSO with adjuvant BEP chemotherapy (Bleomycin, etoposide, cisplatin).ConclusionsJGCT is a rare ovarian tumor affecting young women and children with diverse histopathologic features. Despite an aggressive histopathology, these tumors have a good outcome, when diagnosed at an early stage.     

Neuroendocrine neoplasms of the thymus

Neuroendocrine tumors of the thymus bear many similarities to "carcinoids" and "oat-cell carcinomas" in other organs, and are clinicopathologically distinct from thymomas, thymic seminomas, and other primary tumors of this gland. They are associated with Cushing's syndrome or multiple endocrine neoplasia in 35% of cases, and are often locally aggressive. Approximately 30-40% of patients have distant metastases of their tumors that ultimately result in fatality, since the response of thymic neuroendocrine neoplasms to irradiation and chemotherapy is poor. Ultrastructural studies and immunohistochemical stains for chromogranin, protein gene product 9.5, and synaptophysin are effective tools for the diagnosis of thymic carcinoid and oat-cell carcinoma.     

Perivascular epithelioid cell tumor (PEComa) of the uterus: an outcome-based clinicopathologic analysis of 41 reported cases

The uterus and retroperitoneum have emerged as the most frequently reported anatomic sites of origin of perivascular epithelioid cell tumors (PEComas), a poorly defined neoplasm that is characterized by varying amounts of spindle and epithelioid cells with clear to eosinophilic cytoplasm that display immunoreactivity for melanocytic markers, most frequently HMB-45. Published reports on 41 previously reported uterine PEComas are reviewed in this report. Of these 41 cases, 31 originating in the corpus and for which there was adequate follow-up information (or clinical malignancy) were categorized into 2 groups: (1) a malignant group that was comprised of cases associated with patient death of disease and/or clinical malignancy as evidenced by local and/or distant extension outside of the uterus (n=13, group 1) and (2) a "nonmalignant" group of cases in which neither of the above features were present (n=18, group 2). Groups 1 and 2 did not significantly differ regarding duration of follow-up (25 mo vs. 24.3 mo, respectively, P=0.9) or patient age (45.61 y vs. 43.46 y, respectively, P=0.7). Five of the group 1 patients experienced distant (extra-abdominal) metastases. The group 1 tumors were significantly larger than the group 2 tumors (averages 9.6 cm vs. 4.67 cm respectively, P=0.04); however, there were no size thresholds that, in of themselves, reliably classified 75% or more of the cases in both groups. Coagulative necrosis was highly associated with group 1, being present in 82% of cases as compared with only 11.8% of group 2 cases (P=0.0002). Eighty-eight percent of the group 2 cases had a mitotic rate of 1/10 HPF and/or coagulative necrosis are features that, if present, raise the definite potential for aggressive behavior.     

31例汗管瘤临床病理分析

３１例汗管瘤临床病理分析王宏雁，高佩嘉，黄应华，沈宏提要对３１例汗管瘤进行临床病理分析，结果发现其主要病理组织学表现为嗜碱性细胞团索（３１／３１，其中蝌蚪状１６例，分支状６例），囊状腺管（２１／３１），角囊肿（３／３１）。畸形发育的汗管是汗管瘤的组织...     

Atypical carcinoid tumour of the thymus: a study of eight cases

Atypical carcinoids of the thymus are rare neoplasms of uncertain prognosis. We have studied eight cases (six male, two female; age range 48–60 years, mean 55 years), none with evidence of a paraneoplastic neuroendocrine syndrome. Tumour size was large and ranged from 7.5 to 10 cm. Microscopically, all had a nesting/insular or trabecular pattern, eosinophilic cytoplasm, round nuclei with fine chromatin and small nucleoli. No small cell features were evident. Mitotic activity ranged from 2 to 21 per 1.52 mm². Focal necrosis was seen in all cases. All were positive for cytokeratin (AE1/AE3, CAM 5.2) and the neuroendocrine markers NSE, synaptophysin and chromogranin; five cases were positive for calcitonin. On electronmicroscopy all contained dense core granules, often numerous. Three cases were stage I and five stage III (infiltrating lung or chest wall). Follow-up information was available in four cases (one stage I and three stage III): the stage I tumour had local recurrence and metastasis to the lung within a year whilst the three patients with stage III tumours died of liver, bone and brain metastases within 3 years.     

Primary neuroendocrine carcinomas of the thymus.

Primary neuroendocrine carcinomas of the thymus are rare and comprise a wide spectrum of lesions ranging from well-differentiated to poorly-differentiated neoplasms. The classification of such tumors in the thymus is still controversial. By convention, the better-differentiated examples have been traditionally designated as thymic carcinoids and thought to represent the mediastinal counterpart of carcinoid tumors in other foregut locations. However, recent studies have shown that such neoplasms, when arising in the thymus, exhibit a much more aggressive behavior than those originating at other locations. We therefore consider these lesions to represent fully malignant neoplasms that fall within the spectrum of neuroendocrine carcinomas. The designation of well-, moderately-, or poorly-differentiated thymic neuroendocrine carcinoma is therefore favored for these tumors in the present review. Because such tumors may often adopt unusual morphological appearances, it is important to distinguish them from other more common conditions presenting at this location that may exhibit similar histological features. The clinicopathologic, immunohistochemical, and differential diagnostic features of these tumors in the mediastinum are discussed.     

儿童颅内肿瘤254例临床病理分析

目的分析儿童颅内肿瘤的临床特点和病理类型,提高儿童颅内肿瘤的早期诊断率和诊疗效果。方法对254例儿童颅内肿瘤的临床及病理资料进行总结分析。结果本组病例占我院同期脑肿瘤病例的11.70%,以男性患儿居多,占64.57%;发病年龄以9～12岁为高发,占27.95%;临床表现以头痛、头晕、呕吐为主,占73.23%;儿童颅内肿瘤以胶质细胞瘤为多见,占50.79%,其次为髓母细胞瘤,占24.42%;发病部位幕下多于幕上,占57.09%;CT检查阳性率为94.09%,MR检查阳性率为100%。结论儿童颅内肿瘤发病男多于女,肿瘤好发于幕下,以胶质瘤和髓母细胞瘤最为多见,其临床表现、发病部位、肿瘤性质和组织学类型均与成人有很大不同;影像学检查仍是目前儿童颅内肿瘤的常规检查方法,MR诊断阳性率高于CT。     

Primary carcinomas of the thymus gland.

Carcinomas of the thymus are now well recognized as distinctive but rare entities, and several clinicopathologic variants of such neoplasms have been described. These include keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, lymphoepithelioma-like carcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, mucoepidermoid carcinoma, clear-cell carcinoma, papillary adenocarcinoma, adenocarcinoma not otherwise specified, basaloid carcinoma, and sarcomatoid carcinoma. The application of electron microscopy, immunohistology, and other adjunctive pathological techniques is effective in refining the differential diagnosis between primary thymic carcinoma (PTC) and several other histological simulators. However, the distinction between PTC and carcinomas that involve the thymic region by metastasis from other sites is a difficult one, and ultimately must be predicated on detailed clinical and radiographic information. Well-differentiated squamous carcinoma, low-grade mucoepidermoid carcinoma, and basaloid carcinoma of the thymus usually are associated with a favorable prognosis, but other variants are aggressive and require multimodality treatment approaches.