Dual differentiation in small cell carcinoma (oat cell carcinoma) of the lung

Two cases of small cell “undifferentiated” carcinoma (oat cell carcinoma) of the lung with dual neurosecretory and squamous differentiation are reported. One was treated with various regimens of chemotherapy and radiotherapy; the other was untreated at the time of biopsy. By electron microscopy, the same tumor cells showed membrane-bound, dense-core, neurosecretory-type granules and bundles of tonofibrils denoting squamous differentiation. This dual differentiation underlies the difficulty of ascribing an exclusively neural histogenesis to small cell carcinomas with neurosecretory-type granules. It is possible that entoderm-associated neuroectodermal tumors develop features of autochthonous entodermal tumors as a result of microenvironmental influences. An alternative hypothesis would be that small cell tumors are derived from basal reserve bronchoepithelial cells with pluripotentialities.     

Small Cell Neuroendocrine Carcinoma of the Urinary Bladder: Report of Three Cases with Ultrastructural Analysis

Three cases of small cell neuroendocrine carcinoma of the urinary bladder were studied by light and electron microscopic techniques. Dense-core, membrane-bound granules were identified in the cytoplasm of all 3 cases, substantiating the light microscopic impression of a morphologic similarity to other neuroendocrine carcinomas, such as small cell (oat cell) carcinoma of the lung. Two of the three cases showed clinical evidence of distant metastases, suggesting an aggressive biologic potential of this tumor similar to oat cell carcinoma of the lung. A partial remission was induced in these 2 cases using chemotherapy protocols similar to the drug regimens for small cell (oat cell) carcinomas of the lung. Recognition of this distinct entity has important clinical implications regarding therapeutic approach.     

Amphicrine Differentiation in Bronchioloalveolar Cell Carcinoma

We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.     

Amphicrine Differentiation in Bronchioloalveolar Cell Carcinoma

We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.     

上皮性标记物在人肺小细胞癌免疫组化研究中的应用

为证实肺小细胞癌的上皮特性,以上皮性标记物角蛋白(KT,细胞角蛋白(CKT),上皮性膜抗原(EMA),分泌成份(SC),糖脂类抗原(SLX)、糖脂类抗原(SLEA)、癌胚抗原(CEA)等用于本实验中。人肺两型小细胞癌(燕麦细胞癌和中间细胞型小细胞癌)均不同程度地表达了这些抗原,显示其上皮性分化的特性。根据抗原的阳性率和在细胞内存在形式不同,提示中间细胞型小细胞癌在生物学和组织学上更类似于腺癌和鳞癌的特征。上皮性膜抗原是小细胞癌较理想的标记物,而联合应用这些标记物能够增强诊断的准确性及评价标本的质量。     

Electron Microscopy of Small Cell Carcinoma of the Lung with Special Reference to the Crush Phenomenon

Four cases of small cell carcinoma of the lung were studied ultrastructurally. The tumor cells contained scattered neurosecretory granules. Areas of the tumor that showed the characteristic crush phenomenon were found to be surrounded by myofibroblasts. It is proposed that the crush phenomenon is caused by contraction of the encircling myofibroblasts. The myofibroblasts and collagen may also cause degeneration and necrosis of the tumor cells. Myofibroblasts have not been observed in other histologic types of carcinoma of the lung.     

Small Cell (Endocrine Cell) Carcinoma of the Gallbladder with Squamous and Adenocarcinomatous Components

Small cell (endocrine cell) carcinoma of the gallbladder in a 62-year-old woman is reported. The palliative cholecystectomy specimen revealed a submucosally invading tumor with extensive hemorrhagic necrosis. At autopsy, performed five months after surgery, a huge tumor measuring 14×12×8cm was located at the liver hilus. No signs or symptoms related to overproduction of hormones were recorded throughout her illness. Neither lung lesions nor gall stones were identified. Histologically, diffuse proliferation of small, spindle shaped atypical tumor cells with numerous mitoses was evident. Intraepithelial tumor cell proliferation in the gallbladder mucosa was seen focally. The neuroendocrine nature of the tumor cells was confirmed by the histologic pattern of growth with pseudo-rosette formation, positive reaction for Grimelius' argyro-philia, neuron-specific enolase and Leu 7, and ultra-structural demonstration of neuroendocrine-type granules. Immunostaining for a variety of hormones was all negative. Characteristically, foci with squamous and adenocarcinomatous differentiation were identified in the tumor tissue. The glandular components were immuno-reactive for carcinoembryonic antigen, secretory component, epithelial membrane antigen and CA19–9. The histogenesis and totipotentiality of the neoplasm were discussed.     

Electron Microscopy of Small Cell Carcinoma of the Lung with Special Reference to the Crush Phenomenon

Four cases of small cell carcinoma of the lung were studied ultrastructurally. The tumor cells contained scattered neurosecretory granules. Areas of the tumor that showed the characteristic crush phenomenon were found to be surrounded by myofibroblasts. It is proposed that the crush phenomenon is caused by contraction of the encircling myofibroblasts. The myofibroblasts and collagen may also cause degeneration and necrosis of the tumor cells. Myofibroblasts have not been observed in other histologic types of carcinoma of the lung.     

Small Cell Neuroendocrine Carcinoma of the Urinary Bladder: Report of Three Cases with Ultrastructural Analysis

Three cases of small cell neuroendocrine carcinoma of the urinary bladder were studied by light and electron microscopic techniques. Dense-core, membrane-bound granules were identified in the cytoplasm of all 3 cases, substantiating the light microscopic impression of a morphologic similarity to other neuroendocrine carcinomas, such as small cell (oat cell) carcinoma of the lung. Two of the three cases showed clinical evidence of distant metastases, suggesting an aggressive biologic potential of this tumor similar to oat cell carcinoma of the lung. A partial remission was induced in these 2 cases using chemotherapy protocols similar to the drug regimens for small cell (oat cell) carcinomas of the lung. Recognition of this distinct entity has important clinical implications regarding therapeutic approach.     

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.     

ZMYM3 May Promote Cell Proliferation in Small Cell Lung Carcinoma

Zinc finger, myeloproliferative, and mental retardation-type containing 3 (ZMYM3) is a highly conserved protein among vertebrates. Although it promotes DNA repair and moderate histone acetylation, the other functions of ZMYM3 remain unclear. We herein examined the physiological functions of ZMYM3 in human lung cancer using a ZMYM3-knockdown small cell lung cancer (SCLC) cell line. ZMYM3-knockdown SCLC cells grew slowly and the Ki-67 labeling index was lower in ZMYM3-knockdown cells than in mock cells. The subcutaneous tumors that formed after xenotransplantation into immunodeficient mice were slightly smaller in the ZMYM3-knockdown group than in the mock group. Furthermore, public RNA-sequencing data analyses showed similar RNA profiles between ZMYM3 and some cell proliferation markers. These results indicate that ZMYM3 promotes cell proliferation in human lung carcinomas, particularly SCLC.     

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.     

Small cell (oat cell) carcinoma of the breast

A case of small cell (oat cell) carcinoma, which represents both the most dlstlnctlve and the least common type of mast carcinoma wtth neuroendocrine dlfterentiation and usually shows the most aggressive behavior, is described. Radlcal mastectomy was performed on a Wyearold female for a 10 cm tumor located in the outer part of the right breast with cutaneous ulceration Microscoplcally, the tumor predominantly consisted of a diffuse proliteration of small, round to ovoid cells with hyperchromatlc nuclei and ill-defined, scant cytoplasm that was reminiscent of oat cell carclnoma of the lung. There were foci of invasive ductal carcinoma and ductal carcinoma in situ . Small cell carcinoma areas constituted approximately 90% of the neoplasm. The patlent had axlllary lymph node metastasis. The small tumor cells were argyrophlllc and positive for CAM5.2, carclnoembryonic antigen, neuron-specific enolase, Leu-7, chromogranln A and synaptophysin. Flow cytometric analysis showed an aneuplold DNA content. The patient was alive and well without disease 4 years after surgery. Small cell carcinomas of the breast may exhibkt a spectrum of malignancy that is comparable to similar tumors at better known primary sites.     

多层螺旋CT用于小细胞肺癌与肺鳞癌的鉴别诊断价值分析

目的 分析多层螺旋CT用于小细胞肺癌与肺鳞癌的鉴别诊断价值。方法 选取2015年1月~2017年12月本院接收的肺癌患者106例,由病理类型分组,小细胞肺癌53例作为A组,另53例为肺鳞癌作为B组,两组患者均需进行多层螺旋CT鉴别诊断,回顾分析两组影像学特征以及A组相关危险因素。结果 A组和B组在密度、性状、强化形式、支气管形态、阻塞性改变、淋巴结融合、淋巴结肿大、大血管侵袭等影像特征对比上,差异具有统计学意义（P＜0.05）,但在远处转移、胸膜转移和心包积液等特征比较上,差异无统计学意义（P＞0.05）。经多因素分析得知,小细胞肺癌的危险因素主要为支气管狭窄通畅、肿瘤均匀强化和淋巴结融合。结论 多层螺旋CT用于小细胞肺癌与肺鳞癌具有较高的鉴别诊断价值,能清晰显示出小细胞肺癌与肺鳞癌的影像特征差异,为临床鉴别诊断提供科学的参考依据。     

Squamous Differentiation in Thyroid Carcinoma With Special Reference to Histogenesis of Squamous Cell Carcinoma of the Thyroid

Squamous differentiation of thyroid carcinoma was studied clinicopathologically and immunohistochemically in 29 autopsy cases. Tumor cell nests with squamous differentiation (CNSD), which histologically resembled squamous cell carcinoma, were found in 6 cases (20.7%). All of these 6 cases with CNSD had areas of undifferentiated carcinoma, representing 31.6% of 19 cases with undifferentiated carcinoma, and all but one case also showed coexisting papillary carcinoma. The CNSD were histologically associated with undifferentiated carcinoma in 5 cases, and with papillary carcinoma in one case; the CNSD were occasionally intermingled with these types of carcinoma, and there were findings suggesting a histological transition between the CNSD and undifferentiated carcinoma or papillary carcinoma. Immunohistochemistry revealed that all the CNSD were reactive with antibodies for keratin and vimentin, whereas thyroglobulin and desmin were not expressed. It was concluded that the CNSD examined here were most probably due to extensive squamous differentiation (squamous metaplasia) in undifferentiated carcinoma and papillary carcinoma. In addition, the present results may explain the fact that cases diagnosed solely as squamous cell carcinoma sometimes show a prognosis similar to that of undifferentiated carcinoma, and may well represent extensive squamous differentiation in such tumors rather than true squamous cell carcinoma of the thyroid. Acta Pathol Jpn 39: 306 312, 1989.     

Immunohistochemical and Ultra structural Study of Mixed Small cell/Large cell Carcinoma of the Lung

The authors examined the immunohistochemical and ultra-structural characteristics of mixed small cell/large cell carcinoma (mixed subtype) of the lung which has been newly categorized as anaplastic small cell lung carcinoma. The 34 cases of small cell lung carcinoma examined consisted of 18 cases of pure small cell carcinoma (pure subtype), 12 cases of the mixed subtype and 4 cases of combined small cell carcinoma. Immunohistochemically, the number of immunoreactive tumor cells for chromo-granin A was smaller (P<0.05) and that for creatine kinase BB was relatively larger in the mixed subtype. Sialyl Les i antigen (SLX), one of the SSEA 1 related carbohydrate antigens, was expressed specifically in the mixed subtype. Ultrastructurally, tumor cells in the mixed subtype had smaller amounts of neurosecretory granules and larger amounts of desmosomes than those in the pure subtype (P<0.05, P<0.005, respectively). These results suggest that the mixed subtype may show more epithelial than neuroendocrine differentiation and that SLX may be a specific marker for the mixed subtype to be used in pretherapeutic diagnosis. Acta Pathol Jpn 41: 540 551, 1991.     

Acinar Cell Carcinoma of the Pancreas

A case of acinar cell carcinoma of the pancreas is presented. The differential diagnosis is discussed and includes endocrine neoplasm of the pancreas (islet cell and carcinoid tumor) and a poorly differentiated adenocarcinoma. The separation of the various entities by light microscopic, histochemical, immunocytochemical, and ultrastructural methods is described. The acinar cell carcinoma characteristically is positive for pancreatic digestive enzymes by immunocytochemistry, and at the ultrastructural level zymogen-type granules can be demonstrated; these have a tendency to aggregate in the apical region of acinar structures. Clinically the acinar cell carcinoma is an aggressive malignant neoplasm that may present with a characteristic syndrome of disseminated fat necrosis. Survival is generally less than 1 year.     

Small Cell Undifferentiated Carcinoma of the Pancreas

Small cell undifferentiated carcinoma of the pancreas is a rare neoplasm: Only 12 cases have previously been documented. This paper describes the clinical evolution, immunohistochemical profile, and ultrastructural features of a case occurring in a 37-year-old woman.