Exocytosis of neurosecretory granules in small cell undifferentiated carcinoma

The tumor cells in the pleural effusions of a case of small cell undifferentiated carcinoma have been studied by light microscopy and by thin section and freeze-fracture electron microscopy. Evidence of exocytosis of neurosecretory granules from the tumor cells is presented. The tumor cells form clumps, with the cells joined by focal tight junctions and small desmosomes. These findings are discussed with reference to the neuroendocrine origin of these tumors and the role of the junctional complexes in the formation of tumor cell aggregates.     

Sarcomatoid carcinoma with components of small cell carcinoma and undifferentiated carcinoma of the gallbladder

We report a case of sarcomatoid carcinoma with components of small cell carcinoma and undifferentiated carcinoma of the gallbladder. An 84-year-old woman was admitted to our university hospital with right upper abdominal pain and back pain. Clinical diagnosis of a gallbladder tumor was made based on the findings of abdominal ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography, and a cholecystectomy was carried out. On gross examination a pedunculated polypoid tumor protruded into the lumen of the gallbladder. Histologically the tumor was composed of carcinomatous and sarcomatous components; the carcinomatous component consisted mainly of small cell carcinoma and undifferentiated carcinoma. In general, the carcinomatous component of sarcomatoid carcinoma of the gallbladder consists of adenocarcinoma, and there have only been two previously reported cases in which the carcinomatous component consisted of small cell carcinoma or undifferentiated carcinoma. Because the patient's prognosis may be influenced by the peculiar carcinomatous component in such cases, it is important to accumulate case reports that clarify their clinicopathological features.     

Primary small cell carcinoma of the cecum

Cecal extrapulmonary small cell carcinoma (cESC) is extremely rare, with only single previous report of occurrence in a child. We report a 76-year-old man admitted for evaluation of a cecal mass seen in colonoscopy. Histology revealed small cell carcinoma with classic immunohistochemical profile similar to those seen in the colon. Further clinical survey documented absence of any other masses or abnormality. To the best of our knowledge, this is the first case of primary cESC occurring in an adult. Awareness of the pathologist and clinician of the cecum as a potential site of cESC may help to prevent misdiagnosis as poorly differentiated adenocarcinoma. This is crucial because extrapulmonary small cell carcinomas usually have worse prognosis.     

Primary neuroendocrine small cell carcinoma of the breast

A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.     

原发性浅表食管小细胞神经内分泌癌15例的临床病理学特征

目的 分析原发性浅表食管小细胞神经内分泌癌的临床病理学及免疫组织化学特征,以寻找浅表食管小细胞神经内分泌癌合适的诊断标志物及治疗方法.方法 回顾性分析15例原发性浅表食管小细胞神经内分泌癌的临床病理学特征,并采用免疫组织化学MaxVision方法检测嗜铬粒素A(CgA)、神经元特异性烯醇化酶(NSE)、突触素、CD56、甲状腺转录因子-1(TTF-1)、细胞角蛋白AE1/AE3、CK34βE12及CK10/13在食管小细胞神经内分泌癌中的表达.结果 原发性浅表食管小细胞神经内分泌癌的发病率占同期浅表食管癌的4.8％(15/312).患者中位生存时间19个月,平均生存时间23.7个月.1、2和5年生存的分别有10、5和1例.免疫组织化学标志物NSE、突触素、AE1/AE3均为阳性,CD56阳性14例,TTF-1阳性9例,CgA阳性8例,CK34βE12阳性1例,CK10/13均为阴性.结论 原发性浅表食管小细胞神经内分泌癌恶性度高,进展快速,预后很差.建立在放化疗联合外科切除基础上的系统性治疗或许有助于延长患者的生存期.NSE、突触素、AE1/AE3、CD56、TTF-1、CgA在食管小细胞神经内分泌癌中的高表达对其诊断及鉴别诊断具有一定应用价值.     

Primary undifferentiated carcinoma of the small intestine: an immunohistochemical study and review of the literature

Primary undifferentiated carcinoma of the small intestine is an extremely rare neoplasm. Here, we report a case of primary undifferentiated carcinoma that arose from the ileum in a 65-year-old woman. Laboratory data revealed anemia and slightly elevated inflammatory parameters. Computed tomography showed a heterogeneous mass in the pelvic cavity, and magnetic resonance imaging revealed that the margin of the tumor mass was clear. Positron emission tomography using ¹⁸F-fluoro-2-deoxy-d-glucose (FDG) showed accumulation of FDG on the tumor mass with a standardized uptake value of 8.3. Partial resection of the ileum to remove the tumor was performed under a clinical diagnosis of small intestinal carcinoma. The tumor was nodulated and had a circumscribed margin 6.5 × 5.5 × 4 cm in diameter. Microscopically, the tumor was composed of giant polygonal cells with cellular atypia. Immunohistochemical examination revealed that the tumor cells expressed epithelial markers including AE1/AE3, CAM5.2, and EMA; however, lymphocytic, mesenchymal, and gastrointestinal stromal tumor markers were not expressed. We made a final diagnosis of primary undifferentiated carcinoma of the small intestine. The prognosis of patients with undifferentiated carcinoma of the small intestine is very poor. To improve the outcome of treatment, early and accurate diagnosis is essential, and additional therapy, including multimodality adjuvant therapy or the administration of novel molecular targeted drugs, should be considered.     

Morphometric and flow cytometric analysis of small cell undifferentiated carcinoma of the bladder.

Eighteen cases of primary small cell carcinoma of the bladder were studied. Three patients survived for two years and one survived for five years, which was significantly worse when compared with poorly differentiated transitional cell carcinoma (WHO grade 3). Aggressive tumour behaviour was independent of the presence of neuroendocrine characteristics. Morphometric analysis showed that the nuclear size, which was comparable with that reported in pulmonary small cell carcinoma, was significantly smaller than in poorly differentiated transitional cell carcinoma. Nuclear morphometry may therefore help identify small cell bladder carcinoma, especially in the absence of neuroendocrine differentiation characteristics. DNA flow cytometry of paraffin wax embedded specimens showed aneuploidy in 14 tumours--five were peritetraploid and two multiple aneuploid--and only three were diploid. Aggressiveness of small cell bladder carcinoma usually coincides with aneuploidy in most cases, but diploid tumours may also follow a rapid, lethal clinical course.     

Primary adenoid cystic carcinoma of the esophagus

Immunohistochemical and electron microscopic findings of a primary adenoid cystic carcinoma of the esophagus from a 71-year-old male patient are described. An oval tumor in the middle intrathoracic esophagus was resected. The tumor appeared similar to a submucosal tumor and was histologically diagnosed as primary adenoid cystic carcinoma (ACC) of the esophagus. The patient has survived for 10 years postoperatively with no evidence of recurrence. Histologically, the tumor showed a cribriform, tubular or solid pattern. A small focus of squamous cell carcinoma (SCC) was found independently. Immunohistochemical results for keratin groups, S-100 protein and smooth muscle actin (αSMA) revealed similar profiles in the ACC tumor tissues and small ducts of the normal esphageal glands. By electron microscopy, tumor cells were found markedly similar to the small duct cells of the normal esophageal gland. These findings. indicate that ACC may originate from the esophageal glands, especially from cells of the small duct including intercalated duct.     

Paranuclear blue inclusions in metastatic undifferentiated small cell carcinoma in the bone marrow.

Paranuclear blue inclusions (PBIs) are frequently identified within metastatic undifferentiated small cell carcinoma (SCC) cells on air-dried bone marrow aspirates stained with Wright's stain. To determine the sensitivity and specificity of this finding, 116 bone marrow aspirates containing metastatic neoplasms were evaluated for the presence and frequency of PBIs. Bone marrow specimens included 47 cases of metastatic SCC of the lung, 13 cases of large cell lymphoma, 19 cases of neuroblastoma, five cases of small, noncleaved cell lymphoma, seven cases of rhabdomyosarcoma, three cases of Ewing's sarcoma, three cases of other sarcomas, and 19 cases of non-small cell carcinoma (adenocarcinoma). PBIs were identified in 40 of 47 (85%) cases of SCC and their frequency varied from 0 to 24% of tumor cells among different cases. In approximately half the cases of SCC, PBIs were identified in 1 to 4% tumor cells; and in eight cases, PBIs were present in 5% or more of tumor cells. PBIs were also identified in two of seven (29%) cases of rhabdomyosarcoma and one case of malignant peripheral nerve sheath tumor, but they were not seen in Ewing's sarcoma, small non-cleaved cell lymphoma, large cell lymphoma, neuroblastoma, or non-small cell carcinoma. In addition, PBIs were not seen in alcohol-fixed, Papanicolaou-stained cytology specimens containing SCC. Ultrastructurally, PBIs may represent phagocytized nuclear/cellular material. PBIs are a feature of small cell carcinoma on air-dried, cytologic material stained with Romanowsky type stains. Their presence may provide diagnostic information with regard to the differential diagnosis of metastatic SCC in the bone marrow. Future studies evaluating non-bone marrow Wright's stained fine-needle aspiration specimens are needed to determine if PBIs are useful in distinguishing SCC from other poorly differentiated tumors in the cytology laboratory.     

食管小细胞癌的组织病理及神经内分泌分化的研究

从１４７３例食管癌癌组织切片中发现小细胞癌３０例，用２种上皮性和６种神经内分泌标志物，采用ＡＢＣ免疫酶标法进行检测。结果发现：食管小细胞癌在光镜下显示多种不同的组织形态，免疫组化染色其神经内分泌标记率较高。对食管小细胞癌的发病率、诊断和鉴别诊断及其生物学行为进行了讨论，并探讨其可能的组织来源。     

Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung

Giant cell carcinoma (GCC) is a highly aggressive variant of sarcomatoid carcinoma of the lung. To date, however, there have been no reported cases of ovarian carcinoma mainly composed of GCC. Herein is reported the case of a 54-year-old Japanese woman with an undifferentiated ovarian carcinoma producing granulocyte colony-stimulating factor (G-CSF) and an inflammatory cytokine. Histologically, the tumor was composed of cohesive nests or discohesive pleomorphic mononucleated or multinucleated tumor giant cells, accompanied by inflammatory cell infiltration and emperipolesis. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen and cytokeratin 7. Clinically, after the initial surgery, the tumor had rapid regrowth along with the production of G-CSF and an inflammatory cytokine. Adjuvant chemotherapy was administered but induced severe heart failure and severe neutropenia, probably due to the presence of hypercytokinemia and excess G-CSF. Upon the appearance of these fatal side-effects the chemotherapy was immediately discontinued and replaced with radiotherapy. The recognition of this type of ovarian tumor is important for clinical management, because adjuvant chemotherapy is the standard treatment for clinical management of epithelial ovarian cancer.     

Primary small cell carcinoma of skin. Histogenetical study

Four cases of primary small cell carcinoma of the skin (PSCCS) are presented (ages ranging from 60 to 68 years). Ultrastructurally, two cell types were identified, with both presenting electron-dense secretory granules and paranuclear intermediate filaments. Argyrophylia was positive in one case. Intense solar elastosis in two cases and actinic keratosis in one case suggest a possible role from solar damage in the pathogenesis of this tumor. According to comparative ultrastructural features, different histogenetic possibilities in Merkel cells (MC), peripheral neuroblastic tissue, and totipotential cells are discussed. Some neurosecretory-like granules were observed in basal cell carcinoma (BCC). We consider that PSCCS reproduces cells similar to MC and probably originates in stem cells with totipotential capacity.     

Primary choriocarcinoma of the urinary bladder in association with undifferentiated carcinoma

A carcinoma of the urinary bladder with a distinct choriocarcinomatous component that developed in a postmenopausal woman was associated with high titers of circulating chorionic gonadotropin. The diagnosis was supported by histochemical demonstration of human chorionic gonadotropin in syncytial tumor giant cells and electron microscopic features consistent with syncytiotrophoblastic cell differentiation.     

原发性乳腺小细胞癌一例

患者女,72岁.无意间发现右侧乳腺肿物2周入院,无不适.查体:双侧乳腺无乳头凹陷及橘皮征,右侧乳腺内上象限可触及一肿物,大小2.2 cm×1.0 cm,质硬,界限不清,形态不规则,活动度差.