附睾腺瘤样瘤5例组织学和免疫组化观察

本文对5例附睾腺瘤样瘤的组织学和免疫组化特征进行了观察。结果表明，肿瘤对细胞角蛋白（cytokeratin）、上皮膜抗原（EMA）和波形蛋白（vementin）均呈阳性反应，对第八因子相关抗原（FvlllRAg）均呈阴性表达。这些结果明确揭示了肿瘤细胞的双向分化特征，进一步支持该瘤间皮起源的观点。在病理诊断中，该瘤须与上皮样血管瘤和腺癌进行鉴别。     

应用组化及免疫组化方法诊断子宫腺瘤样瘤

目的：子宫腺瘤样瘤发生率低，在临床与病理上均易误诊和漏诊，病理上误诊漏诊的主要原因是其病理形态多样性以及与形态相似的其他肿瘤难鉴别。应用特殊染色和免疫组织化学染色对子宫腺瘤样瘤的诊断与鉴别诊断有重要意义。方法：从本院１０年档案材料１５６０例子宫良性肿瘤中共收集子宫腺瘤样瘤９例，观察其临床病理特征，选用细胞角蛋白（ＣＫ），波纹蛋白（ＶＩＭ），表皮膜抗原（ＥＭＡ），癌胚抗原（ＣＥＡ），血管相关因子（Ｆ８）和ＨＨＦ３５作为第一抗体，应用免疫组化方法（ＳＬＡＢ法），以及特殊染色如糖原染色（ＰＡＳ染色），嗜银染色（Ａｇ染色）和ＡｌｉｃｉａｎＢｌｕｅ染色（ＡＢ染色）。对每例进行染色，观察结果。结果：９例子宫腺瘤样瘤占１５６０例子宫良性肿瘤，其中６例误诊为其他肿瘤。免疫组化结果显示９例子宫腺瘤样瘤瘤细胞ＣＫ及ＶＩＭ均呈强阳性，而对ＣＥＡ，ＥＭＡ，Ｆ８及ＨＨＦ３５均无表达。ＡｌｃｉａｎＢｌｕｅ染色９例均有阳性反应，ＰＡＳ染色阴性，Ａｇ染色见瘤细胞周围银纤维少。结论：本文收集子宫腺瘤样瘤比以前文献报道发生率低，ＣＫ，ＶＩＭ及ＡｌｃｉａｎＢｌｕｅ染色是子宫腺瘤样瘤的阳性标记物，而ＣＥＡ，ＥＭＡ，ＨＨＦ３５，Ｆ８及ＰＡＳ染色瘤细     

Epithelial profile of epithelioid sarcoma. An immunohistochemical analysis of eight cases

Eight cases of epithelioid sarcoma were examined immunohistochemically, in order to clarify the adjunct epithelial profile of the tumor and to ascertain the intermediate filaments contained in the tumor cells. All tissues showed a strongly positive immunoreactivity for epithelial membrane antigen (EMA) and tissue polypeptide antigen (TPA). In the case of carcinoembryonic antigen (CEA), one showed a strong reaction, whereas the others were variably less stained. Cytokeratins (45 kd and 54 kd) specific for simple epithelia, including coelomic epithelium, were regularly found in all cases; a small number of cells were positive for high molecular weight cytokeratin (57 kd) and none for 66 kd cytokeratin. Coexpression of both cytokeratin and vimentin was confirmed using fresh-frozen materials. Therefore, both microscopic and immunohistochemical evidence supports the hypothesis that epithelioid sarcoma masquerades as a carcinoma.     

A malignant mixed mesodermal tumor of the ovary

We report a primary malignant mixed mesodermal tumor in the right ovary of 75-year-old woman. She was admitted to Kobe West Municipal Hospital because of an abdominal fullness and an upper abdominal pain. A laparotomy yielded yellowish-clear ascites (2,000 ml) a tumor located in the right ovary, an upper abdominal mass the size of a child's head between the stomach and the transverse colon, and disseminating small tumors of the peritoneum. The left ovary and uterus showed no particular change. Four months after the onset of her symptoms, the patient died of carcinomatous cachexia and dyspnea. On microscope examination, the tumor of right ovary showed combined features of an adenocarcinoma, an adenosquamous carcinoma and a serous cystadenocarcinoma with foci of a heterologous stromal differentiation, that is an area of immature, striated muscle cells, bone, and cartilage and undifferentiated spindle cells. Immunohistochemical stains were useful for determining elements of the tumor cells. Epithelial tumor cells were positive for cytokeratin, epithelial membrane antigen, and CEA, while mesenchymal tumor cells were generally positive for vimentin and the immature muscle cells were especially positive for desmin, actin, and myosin. Additionally, myoglobin was identified in the rhabdomyoblast. Finally, S-100 protein was present in cartilage area and partially present in the adenocarcinomatous element.     

Immunoperoxidase study on adenomatoid tumor of the epididymis using anti-mesothelial cell serum

The mesothelial origin of epididymal adenomatoid tumor is supported by the current study for the presence of mesothelial antigen in the tumor cells. By an indirect immunoperoxidase technique, anti-mesothelial cell serum showed positive cytoplasmic staining in five of the six adenomatoid tumors studied. Previous findings of the presence of strong cytoplasmic keratin and the absence of carcinoembryonic antigen and Factor VIII-related antigen in these tumor cells are also confirmed by this study.     

Case of a 23-year-old woman with serous surface papilloma of borderline malignancy of the left ovary and mucinous cystadenoma of the right ovary

A rare case is reported of a 23-year-old woman with serous surface papilloma of borderline malignancy (SSPBM) of the left ovary associated with a foci of peritoneal “implant,” as well as the coexistence of mucinous cystadenoma of the right ovary. The histologic diagnosis of these tumors was classified according to the criteria of the World Health Organization. To confirm the histologic diagnosis, special staining was performed both with AIcian blue, periodic acid-Schiff (PAS), and PAS with diastase digestion, and with immunohistochemical staining for vimentin, cytokeratin, epithelial membrane antigen (EMA), neuron-specific enolase, and carbohydrate antigen 19-9 (CA 19-9). After hematoxylin and eosin staining of the tissue samples, the right ovarian tumor was diagnosed as benign mucinous cystadenoma, and the left ovarian tumor was identified as serous surface papilloma with no apparent stromal invasion, but showing proliferating activity and nuclear abnormality (SSPBM). The histologic features of the peritoneal lesion resembled those of the SSPBM of the left ovary, and showed no invasion of underlying normal tissue. Moreover, both the SSPBM and the peritoneal lesion showed similar patterns on special staining. The summary diagnosis was SSPBM of the left ovary associated with a foci of peritoneal noninvasive “implant” and coexistent mucinous cystadenoma of the right ovary. Regardless of whether or not the peritoneal loci represented an autochthonous multicentric tumor of the peritoneum or a secondary implant from the left SSPBM, the less aggressive histologic character of her tumors has allowed this patient to survive for 8 years after fertility-retaining surgery with no sign of recurrence.     

Alpha-fetoprotein (AFP)-producing ovarian tumor in an elderly woman

Apart from typical yolk sac tumors, ovarian tumors with elevated alfa-fetoprotein (AFP) are uncommon and the differential diagnosis needs to consider the hepatoid pattern of a yolk sac tumor, hepatocellular carcinoma metastatic to the ovary, hepatoid carcinoma, and other epithelial ovarian tumors. We report here an AFP-producing ovarian tumor with uncertain pathological diagnosis, which was extremely responsive to chemotherapy. A 59-year-old Japanese woman presented with lower abdominal distension and was found to have a left ovarian mass on pelvic examination and magnetic resonance imaging (MRI) scan. Laboratory tests showed serum AFP, 73 687 ng/ml; carbohydrate antigen 125 (CA125), 1599 U/ml; and carcinoembryonic antigen (CEA), 13.9 ng/ml. Total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and low anterior resection of the rectum was performed, without any residual macroscopic tumor. Microscopically, the tumor was characterized by a hepatoid carcinomatous component composed of solid sheets of large eosinophilic cells with pleomorphic nuclei. The pathological stage was pT2N0M0. Tumor cells were diffusely immunoreactive for AFP and cytokeratin (CAM5.2), but monoclonal CEA and CA19-9 were focally positive in the cytoplasm, while CA125 was negative. The patient was treated postoperatively with three cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin; with this regimen, serum AFP decreased to 16 ng/ml from 12 600 ng/ml just before the initiation of chemotherapy. The patient received secondary cytoreductive surgery of systemic lymphadenectomy, which revealed no evidence of residual tumor.     

Papillary cystadenocarcinoma of salivary-glands - an immunohistochemical study

The immunohistochemical features of 16 cases of papillary cystadenocarcinoma of salivary glands using a panel of monoclonal and polyclonal antibodies were evaluated. The specimens were from patients postoperatively diagnosed as papillary cystadenocarcinoma of salivary glands where the age of the patients ranged from 20-70 years, males were more commonly affected than the females and parotid gland was the most commonly affected site. The cytokeratins detected by MoAb KL1 and K8.12 were positive in all cases showing a heterogeneity in intensity of reaction. A coexpression of vimentin with cytokeratin was found in 10 cases. The tumor cells had a coexpression of S-100 protein and neuron specific enolase (NSE). Glial fibrillary acidic protein (GFAP) was positive in one case with multiple expression of cytokeratins, vimentin NSE, S-100 protein. The polymorphic mucin MAM-6 was positive in all cases and MAM-3 in 8 cases showing different intensity of reaction. The tumor cells were positive for lysozyme (8 cases), lactoferrin (10 cases) and alpha-1-antichymotrypsin (10 cases). The immunoreactive c-erbB-2 oncoprotein on the cell surface membrane was detected in 2 cases. The labeling index of proliferating cell nuclear antigen in the tumor cells ranged from 3.8 to 43.2% (mean 14.2 +/- standard deviation 9.8). Histopathological feature and a heterogeneity of multiple expression of tissue markers may suggest that a population of cells in papillary cystadenocarcinoma may be counterparts of modified myoepithelial cells of pleomorphic adenoma that express epithelial, mesenchymal and neuronal differentiation although the role of myoepithelial cells in the genesis of this tumor is not clear. However, disorganized stratification and malignant transformation of ductal cells may be the most likely possibility in the histogenesis of this tumor.     

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.     

乳腺恶性纤维组织细胞瘤免疫组化研究（附8例报告）

应用ＡＢＣ法，对８例乳腺恶性纤维组织细胞瘤进行ＡＡＴ、ＡＡＣＴ、Ｖｉｍ、Ｄｅｓ、Ｋｅｒ、ＣＥＡ和ＥＭＡ免疫组化染色。结果ＡＡＴ、ＡＡＣＴ和Ｖｉｍ阳性率１００％，２例Ｄｅｓ阳性。作者同意恶纤组来源于原始间叶细胞，在不同情况下可向组织细胞、纤维母细胞和肌纤维母细胞等不同方向分化，构成了恶纤组复杂多样的细胞成分。     

非卵黄囊瘤的AFP阳性卵巢恶性肿瘤4例临床病理观察

目的 探讨非卵黄囊瘤的ＡＦＰ阳性卵巢恶性肿瘤的病理组织形态和临床生物学行为。方法 报道４例非卵黄囊瘤的ＡＦＰ阳性卵巢恶性肿瘤,１例为单纯肝样癌,３例为有梭形细胞成分的内膜样癌（其中１例伴有肝样癌）。结果 肝样癌癌细胞的胞质内含有ＡＦＰ、ＡＡＴ和ＡＣＴ成分,而在内膜样癌癌细胞的胞质内以ｃｙｔｏｋｅｒａｔｉｎ和ＣＥＡ成分为主。由于ＡＦＰ具有免疫抑制作用,病人的预后不好。４例中３例已死亡,平均生存２５个     

Diagnostic features of primary malignant lymphomas of the thyroid with monoclonal antibodies

Primary malignant lymphomas (ML) of the thyroid are rare and their conclusive morphologic diagnosis is not always possible. The authors report diagnostic features of 11 cases of ML and one case of plasmacytoma of thyroid compared with chronic lymphocytic thyroiditis and undifferentiated carcinomas of thyroid in an immunohistochemical study using monoclonal antibodies (MoAb). The lymphoid nature of tumors could be identified in all cases with three MoAb on paraffin sections. In ML, tumor cells expressed leucocyte common antigen (Dako-LC+) with negativity for epithelial membrane antigen (Dako-EMA-) and cytokeratin (KL1-). Newer MoAb identifying B-cell (LN-1, LN-2, MB2) and T-cell-associated antigens (MT1, UCHL1) not denatured by fixation, revealed B-cell nature of tumor cells in all cases of ML. Among anti-B MoAb, LN-1 and MB2 were most consistent in their reactivity. In cryostat sections of three ML cases, the tumor cells expressed one or more B-cell-associated antigens. Plasmacytoma was negative for Dako-LC and KL1 but positive for Dako-EMA and monotypic cytoplasmic Ig.     

Immunocytochemical monitoring of micrometastatic disease: Reduction of prostate cancer cells in bone marrow by androgen deprivation

Occult dissemination of tumor cells mainly determines the prognosis of patients with primary prostate cancer. The effect of androgen deprivation on micrometastatic tumor cells in these patients is currently unknown. We therefore used an immunocytochemical assay with monoclonal antibodies (MAbs) directed against epithelial cytoskeleton proteins (i.e., cytokeratins) to monitor the concentration of isolated tumor cells in the bone marrow of 36 prostate cancer patients (stage C), who underwent hormonal androgen deprivation with Flutamide and Leuproreline acetate. Tumor cells in cytologic bone marrow preparations were detected using an assay that employed the MAb CK2 directed against cytokeratin (CK) 18 and the alkaline anti-alkaline phosphatase staining method. Prior to therapy, we detected between 1 and 38 CK-positive cells per sample of 2 × 10⁴ nucleated cells in 21 patients, while the remaining 15 patients displayed tumor-free marrow samples. There was no significant correlation between the concentration of CK-positive cells and the volume of hypo-echogenic lesions as an indicator of the primary tumor volume or the serum level of prostate-specific antigen (PSA). After androgen deprivation, 20 of the 21 initially positive patients either became negative (n = 16) or showed at least a reduction in the concentration of CK-positive cells (n = 4). Moreover, only 2 of the 15 patients with negative pre-treatment findings became positive. All of the 7 patients with remaining tumor cells in the bone marrow after therapy showed no detectable amounts of PSA in their serum. Our findings suggest that serum PSA concentration is no indicator of micrometastatic disease in bone marrow. Neoadjuvant androgen deprivation appears to eliminate disseminated CK-positive tumor cells present in bone marrow, a preferred site of overt metastasis in prostate cancer patients. Int. J. Cancer 71:521-525, 1997. © 1997 Wiley-Liss, Inc.     

Expression of human regenerating gene mRNA and its product in normal and neoplastic human pancreas.

BACKGROUND. Localization of human regenerating gene (reg) mRNA and its product was investigated in normal and neoplastic human pancreas with the in situ hybridization method and immunohistochemical studies. METHODS. Both reg mRNA and reg protein were observed in acinar cells of the pancreas, but neither was found in ductal or islet cells. Immunoreactive reg was observed in an acinar cell carcinoma, a pancreatoblastoma, a solid and cystic tumor, and 5 of 20 duct cell carcinomas, but it was not found in 15 endocrine tumors and 2 microcystic adenomas. RESULTS. For comparison with reg, alpha-1-antitrypsin (AAT), lysozyme, chromogranin A (CMG), CA 19-9, carcinoembryonic antigen (CEA), cytokeratin, vimentin, and alpha-fetoprotein (AFP) were assessed in those tumors. An acinar cell carcinoma and a pancreatoblastoma had positive results for AAT, lysozyme, cytokeratin, and AFP but negative results for vimentin. An acinar cell carcinoma showed cells focally immunoreactive for CMG and CEA. A solid and cystic tumor had strongly positive results for AAT and vimentin and focally positive results for CMG and pancreatic hormones. Microcystic adenomas had abundant glycogen and strong immunoreactivity for cytokeratin. Ductal cell carcinomas showed cells focally positive for AAT, lysozyme, CMG, CA 19-9, and CEA. CONCLUSIONS. The localization of reg protein was not consist with that of any other proteins examined in the current study. Thus, reg protein was considered a useful marker for acinar cell differentiation; however, ectopic expression of reg also was observed in ductal cell carcinomas. In ductal cell carcinomas, expression of reg immunoreactivity was considered as one of phenotypic heterogeneity, as seen in AAT, lysozyme, and CMG immunoreactivity.     

Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance.

A monoclonal antibody (mAb) directed against the cytokeratin (CK) polypeptide no. 18 specifically expressed in cells derived from simple epithelia was used to detect epithelial tumor cells in bone marrow aspirates. Of 156 patients with colorectal carcinoma, 42 presented with cells at the time of primary surgery. The incidence of positive findings varied considerably with the size and the localization of the primary tumor, the involvement of regional lymph nodes, and the presence of clinically manifest metastases. Applying a sensitive double-staining procedure, we could demonstrate that epithelial cells in bone marrow showed a heterogeneic expression of receptors for epidermal growth factor (EGF-R) and transferrin (Tf-R) as well as of the proliferation-associated Ki67 antigen. Also human leukocyte antigen (HLA) class I antigens differed widely in their expression on the CK-positive cells. Clinical follow-up studies on 85 patients showed a significantly higher relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Twenty-three patients were monitored for the presence or absence of CK-positive cells in bone marrow over time. The majority of monitored patients (18 of 23) exhibited a constant pattern of immunocytochemical findings during the time of observation. Thus, the technique may be useful in identifying high-risk patients as well as in monitoring adjuvant therapeutic trials.     

Two new human cholangiocarcinoma cell lines and their cytogenetics and responses to growth factors, hormones, cytokines or immunologic effector cells.

Two new human cholangiocarcinoma (CC) cell lines (CC-SW-I and CC-LP-I) were established and maintained in culture for 2 years. Histologically, both original liver tumors were adenocarcinomas, and the cell lines exhibited morphologic features of moderately differentiated adenocarcinoma. Immunohistochemistry showed that both cell lines were strongly positive for cytokeratin AEI but negative for carbohydrate tumor-associated antigen, CA19-9. Ultrastructural analysis of both cell lines showed the presence of tight junctional complexes and focally formed microvilli. Both CC cell lines were tumorigenic in nude mice. Cytogenetic analysis showed that both cell lines expressed highly aneuploid karyotypes with numerous structural and numerical deviations. CC-SW-I was hypodiploid with numerous chromosome losses and structural rearrangements, while CC-LP-I was hyperdiploid and displayed multiple additional chromosomes. Doubling times for the CC-SW-I and CC-LP-I cell lines in the presence of 15% fetal bovine serum were 72 hr and 180 hr, respectively. Growth of the CC-SW-I cell line was significantly stimulated in the presence of insulin, while that of the CC-LP-I cell line was significantly augmented by epidermal growth factor (EGF). In contrast, dexamethasone strongly inhibited proliferation of both cell lines in a dose-dependent manner. Among various recombinant cytokines examined for effects on growth or surface antigen expression on CC cell lines, only interleukin I-beta (ILI-beta) strongly inhibited growth of the CC-LP-I cell line, while interferons (IFNs) or tumor necrosis factor-alpha (TNF-alpha) were mildly inhibitory. Both tumor cell lines were resistant to natural killer (NK) cells but sensitive to lymphokine-activated killer (LAK) cells. Preincubation of tumor cells with IFN-gamma, IFN-alpha or TNF-alpha significantly decreased the susceptibility of each tumor cell line to lysis by LAK cells, and the change in sensitivity did not correlate with the expression of HLA antigens or intercellular adhesion molecule-I (ICAM-I) on the surface of tumor cells. These 2 CC cell lines are expected to provide valuable information about cell biology of human CC.     

Oncocytic carcinoma arising in submandibular gland with immunohistochemical observations and review of the literature

We report a case of oncocytic carcinoma arising in submandibular gland. The tumour occurred in the left submandibular gland of an 82-year-old Japanese man. Histologically, the tumour was mostly composed of large cells with eosinophilic granules in the cytoplasm and they were arranged in the solid sheets, islands with duct-like structure and cords. The tumour cells had aggressively invaded muscles and perineural tissues, and cervical lymphatic metastasis was frequently observed. Histochemically, the tumour cells were strongly positive for phosphotungstic acid-hematoxylin (PTAH) stain, and we diagnosed this malignant tumour as oncocytic carcinoma. Immunohistochemically, the tumour cells reacted positively for cytokeratin 7, 8, 19, epithelial membrane antigen (EMA), alpha-1-antichymotrypsin and carcinoembryonic antigen (CEA), but negative for cytokeratin 13, 14, smooth muscle actin (HHF35) and S-100 protein (S-100). Tumour was diagnosed as oncocytic carcinoma in submandibular gland. Its characteristics are discussed in term of its histopathological and immunohistochemical features.