Myoepithelial Carcinoma Arising in a Benign Myoepithelioma: Immunohistochemical, Ultrastructural, and Flow-Cytometrical Study

A case of myoepithelial carcinoma arising in a benign myoepithelioma of the minor salivary gland in a 71-year-old patient is reported. The tumor presented initially on the palate and had been diagnosed as “benign lesion” 40 years before. It recurred 22, 36, and 40 years after initial presentation, and a similar histopathological diagnosis was rendered. One year after the last recurrence, the tumor recurred showing typical changes of malignant transformation, and the diagnosis was malignant myoepithelioma. The light microscopy and ultra-structural features of the initial tumor were typical of plasmocytoid myoepithelioma. There were abundant round cells and rare spindle cells with uniform dispersed filaments, sometimes arranged in parallel streams without evidence of dense bodies. These cells showed micropinocytotic vesicles along the cell membrane with poorly developed intercellular junctions and were surrounded by a basal membrane. The malignant counterpart showed fewer plasmocytoid cells and a rather epithelial pattern with marked nuclear pleomorphism and formation of small, or rarely large, glandular lumina. The immunohistochemical features were similar for the benign and malignant tumors, with positivity for S-100 protein, vi-mentin, cytokeratins, and CAM 5.2, and were negative for GFAP, muscle-specific actin, CEA, and desmin. Flow cytometry showed a change in the DNA content profile. The benign myoepithelioma had a diploid DNA content with a low S-phase fraction of 3.9% and proliferative index of 9.1%, while the myoepithelial carcinoma had an evident aneuploid DNA stem line and an increased S-phase fraction of 8.3% with a proliferative index of 18.1%.     

Coexistence of Intracytoplasmic Lumens and Membrane-bound Vesicles in an Invasive Carcinoma Arising in a Cystosarcoma Phyllodes

An unusual invasive breast carcinoma, arising in a cystosarcoma phyllodes and characterized by a variable cytoplasmic appearance and mucin content, was evaluated to determine the nature of the secretory material within the cells as well as the type of secretory organelle at the ultrastructural level. Histochemical studies revealed both acidic (sialic acid) and neutral mucin within the tumor cells. Ultrastructural analysis revealed secretory material within membrane-bound vesicles in some cells and within intracytoplasmic lumens in others; some cells contained both membrane-bound vesicles and intracytoplasmic lumens simultaneously. The Golgi derivation of the intracytoplasmic lumens was supported by their presence within or near hyperplastic Golgi complexes. The histochemical characteristics of the secretory material is correlated with their ultrastructural site of accumulation.     

Coexistence of Intracytoplasmic Lumens and Membrane-bound Vesicles in an Invasive Carcinoma Arising in a Cystosarcoma Phyllodes

An unusual invasive breast carcinoma, arising in a cystosarcoma phyllodes and characterized by a variable cytoplasmic appearance and mucin content, was evaluated to determine the nature of the secretory material within the cells as well as the type of secretory organelle at the ultrastructural level. Histochemical studies revealed both acidic (sialic acid) and neutral mucin within the tumor cells. Ultrastructural analysis revealed secretory material within membrane-bound vesicles in some cells and within intracytoplasmic lumens in others; some cells contained both membrane-bound vesicles and intracytoplasmic lumens simultaneously. The Golgi derivation of the intracytoplasmic lumens was supported by their presence within or near hyperplastic Golgi complexes. The histochemical characteristics of the secretory material is correlated with their ultrastructural site of accumulation.     

Immunohistochemical and Ultrastructural Analysis of Bronchopulmonary Neuroendocrine Neoplasms. I. Carcinoids

Twenty-five strictly defined bronchopulmonary carcinoids were studied by light microscopic immunohistochemistry by the peroxidase technique for NSE (neuronspecific enolase), serotonin, and a broad spectrum of neuropeptides. Eighteen cases were also studied by electron microscopy.

Twenty-three of the twenty-five cases showed immunostaining for NSE; 24 cases displayed immuno-staining for at least two of the hormones tested for; the single case that failed to show hormonal immuno-reactivity was however positive for NSE and had granules by electron microscopy. Serotonin was the most frequently demonstrated hormone followed by bombesin, vasoactive intestinal peptide, gastrin, leuenkephalin, alphamelanocyte stimulating hormone, somatostatin, substance P, and calcitonin. In several cases, adjacent-step sections stained for different hormones strongly indicated immunoreactivity for more than one hormone in single neoplastic cells.

By electron microscopy, all 18 cases studied showed generally abundant neurosecretory granules, which, however, displayed considerable heterogeneity in their size, shape, and density. Twelve of these eighteen cases displayed evidence of squamous differentiation and 10 showed characteristic exocrine lumina.

The capability of single neuroendocrine tumors and single neuroendocrine tumor cells to produce more than one immunoreactive hormone is hereby amply confirmed; these broad capabilities are certainly reflected in the heterogeneous granule populations seen by electron microscopy. The synchronous presence of squamous and exocrine features in bronchopulmonary carcinoids indicates that they too are capable of multidirectional differentiation, which should not detract from their being regarded basically as well-differentiated neuroendocrine neoplasms. The clinical significance of strictly defining bronchial carcinoids is underscored by the fact that of 25 cases followed for 2-13 years, only one developed metastases 9 years postoperatively.     

Frequent Loss of KAI1 Expression in Squamous and Lymphoid Neoplasms : An Immunohistochemical Study of Archival Tissues

The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.     

Basement Membranes in Bronchogenic Squamous Cell Carcinoma: An Immunohistochemical and Ultrastructural Study

Basement membrane (BM) deposition at the interface of tumor cells and stroma was studied in 27 bronchogenic squamous cell carcinomas. Specimens from peripheral and central parts of each tumor were collected. These were frozen, formalin fixed and paraffin embedded or fixed in Karnovsky's fixative, and processed for electron microscopy. With the use of antibodies to type IV collagen and laminin, the BM was visualized by light microscopy with an indirect immunoperox-idase technique. Light microscopic findings were compared to ultrastructural observations. The peripheral parts of the tumors showed continuous BM in a recognizable preexisting alveolar pattern without evidence of invasive growth into the alveolar septa. In contrast, central parts showed highly variable BM deposition ranging from continuous to almost completely absent. Alveolar patterns were not observed in the tumor centers. The stromal compartment of the tumor centers contained many spindle cells with irregular pericellular BM-like material that could be identified ultrastructurally as myofibroblasts. Electron microscopy and immuno-histochemistry yielded virtually identical results. It is concluded that invasive growth in bronchogenic squamous cell carcinomas occurs in central parts of the tumor when the tumor periphery shows expansive growth without invasion of alveolar septa. The situation is different in invasive squamous cell carcinomas originating from other organs because of anatomical differences between the lung and solid organs.     

Expression of Sarcosine Metabolism-Related Proteins in Invasive Lobular Carcinoma: Comparison to Invasive Ductal Carcinoma

Purpose

The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results.

Materials and Methods

Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)].

Results

The sarcosine metabolic phenotype differed between ILC and IDC (p<0.001). In IDC, sarcosine metabolic phenotype was distributed as null type (61.7%)>low sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC.

Conclusion

Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.     

The First Case of HER2+ Invasive Ductal Carcinoma Arising From a Breast Hamartoma and Literature Review

Carcinomas arising from breast hamartomas are exceedingly rare. We present the first reported case of an African-American female presenting with a right breast lump and a subsequent mammogram suggestive of a hamartoma. She later underwent lumpectomy and was found to have HER2+ invasive ductal carcinoma (IDC) arising from a hamartoma. She was amenable to HER2-targeted trastuzumab, hormone therapy and adjuvant radiation but declined chemotherapy. In a review of the literature, IDC is the predominant neoplastic type found in hamartomas. The average hamartoma size at time of neoplasm diagnosis is 6.0 cm. Patients with hamartomas greater than 6.0 cm, with changes in calcification pattern; new nodules or asymmetry should be considered for additional evaluation with ultrasound, MRI and/or biopsy. HER2 status is under-reported among cases and should be evaluated in any malignancy found within hamartomas as HER-2 therapy has improved overall survival and recurrence free survival in HER2+breast cancer patients.     

20例胃平滑肌肿瘤的病理-X线分析

为了提高对胃平滑肌肿瘤的认识,作者回顾性分析了20例经手术、病理证实的胃平滑肌肿瘤的钡餐造影所见。结果表明,胃底与胃体上部是胃平滑肌肿瘤的病变高发区。本病具有典型胃粘膜下肿瘤的X线特征,腔内型者可见胃内边缘光滑的充盈缺损或软组织肿块,粘膜展平或推移;腔外型者可见突出胃外肿块或/和胃与邻近脏器受压;腔内外型者具有上述双重特征,肿瘤较大者多有溃疡形成,甚至囊变,根据肿瘤的大小、形态、生长类型及溃疡表现可作良恶性鉴别。本病的术前诊断主要依靠X线钡餐检查,但无胃肠压迫的腔外型肿瘤,钡餐则难以发现,CT或选择性血管造影可助诊断。     

Immunohistochemical and Ultrastructural Analysis of Bronchopulmonary Neuroendocrine Neoplasms. II. Well-Differentiated Neuroendocrine Carcinomas

We have attempted to characterize a group of bronchopulmonary neoplasms that share certain structural features with true carcinoids but appear distinctly more pleomorphic and behave far more aggressively. In reviewing our files from 1973 to 1982, 11 such neoplasms were identified; the original diagnoses were “atypical bronchial carcinoid” (3 cases), “malignant carcinoid” (1 case), “bronchial carcinoid” (3 cases), “peripheral carcinoid” (2 cases), and “peripheral oat cell carcinoma” (2 cases).

Of the 11 neoplasms, 5 were central and 6 were peripherally located. At presentation, 7 patients had lymph node rnetastases and 1 had a distant metastasis. No patient had a conventionally defined hormonal syndrome; however, 2 patients had a history of episodic flushing, one of which was associated with diarrhea.

All cases were studied by light microscopy and light microscopic immunohistochemistry for NSE (neuron-specific enolase), serotonin, and broad-spectrum neuropeptides. Five cases were studied by electron microscopy. By light microscopy, the tumors were composed of solid clusters of polygonal to fusiform cells in an evident organoid arrangement. Foci of glandular and/or squamous differentiation were seen in 7 cases. Pleomorphism was moderate and mitoses were readily found. Focal necrosis was seen. By immunohistochemistry, 10 cases expressed NSE immu-noreactivity. All cases demonstrated hormonal immu-noreactivity; in 9 cases, immunoreactivity for more than one hormone was observed. The hormones most frequently expressed were serotonin, bombesin, gastrin, leu-enkephalin, and ACTH.

By electron microscopy, all cases studied contained heterogeneous populations of neurosecretory granules; the latter, however, were not abundant and tended to aggregate either in the basal pole of the cells or, more frequently, in interlacing “dendritelike” cytoplasmic processes. Aggregates of intermediate filaments were frequently seen. Basal lamina deposition was seen but gaps and larger areas of discontinuity were frequent.

We believe that these neoplasms constitute a distinct pathologic entity for which the term “well-differentiated neuroendocrine carcinomay” has been proposed. Clinically, these tumors merit special attention since they are demonstrably more aggressive than true carcinoids but are distinctly less malignant than the intermediate or small cell variants of neuroendocrine carcinoma.     

Immunohistochemical Biomarkers of Mesenchymal Neoplasms in Endocrine Organs: Diagnostic Pitfalls and Recent Discoveries

Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this context, the recognition of these rare tumor types can be challenging, with significant potential for misdiagnosis as sarcomatoid carcinomas (i.e., anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or neuroendocrine carcinomas, depending upon the dominant histologic patterns. In this review, we address potential pitfalls in diagnosing selected mesenchymal neoplasms arising within or near endocrine organs, including dedifferentiated liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid sarcoma, Ewing sarcoma, and neuroblastoma. For each of these tumor types, we review clinical and pathologic features, histologic clues to distinguish them from endocrine neoplasms, and recently developed immunohistochemical markers that can be particularly useful for establishing the correct diagnosis.     

Reduplicated Basal Lamina in Clear-Cell Carcinoma of the Ovary: An Immunohistochemical and Electron Microscopic Study

Clear-cell carcinomas of the female genital tract are uncommon tumors that usually arise in the ovary, cervix, or vagina. The objectives of the present study were to examine the immunohistochemical and ultrastructural characteristics of 18 of these tumors and to determine whether any distinctive features were present at the different locations. The fine structure of the neoplastic cells was similar at the several sites but there was a striking difference in the appearance of the basal lamina. Prominent reduplication of the basal lamina was seen in all 7 ovarian carcinomas, whereas it was mild in 3 and absent in 7 of the cervico-vaginal tumors. The distribution of eosinophilic hyaline material in hematoxylin/eosin sections and of immunohistochemical staining for type IV collagen and laminin correlated with the ultrastructural observations. Reduplication of the basal lamina has been observed in a number of epithelial neoplasms and viewed as a criterion of differentiation, but there is currently no evidence that its presence influences the prognosis of clear-cell carcinomas of the ovary.     

Alveolar Variant of Invasive Lobular Carcinoma of the Breast: An Electron Microscopic Study

Four cases of alveolar variant of invasive lobular carcinoma of the breast were examined by electron microscopy, and their appearance compared with those of in situ and classical invasive lobular carcinoma. The individual tumor cells in the alveolar variant were basically similar to those described in the other two lobular tumors. The neoplastic alveoli consisted mostly of light cells, although a few dark cells were sometimes seen at the periphery. The nuclei were large, rounded and rich in euchromatin. The cytoplasm contained a variable amount of mitochondria and endoplasmic reticulum, and a few cells had intracytoplasmic filaments. Numerous tumor cells with membrane-bound electron-dense granules were occasionally seen. A few cells also had intracytoplasmic lumina. Tumor cells were usually seen in close contact with each other. Interdigitating processes and desmosomes were present. In general the tumor cells were not surrounded by basal lamina, but most alveoli were surrounded by elongated fibroblasts or myofibroblasts. These findings confirm both the lobular and the invasive nature of this distinct variant of breast carcinoma.     

Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only 5 of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extrathyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.     

Electron Microscopic and Immunohistochemical Analysis of Glomerular Deposits in Patients with Bronchogenic Carcinoma

Kidneys of 27 consecutive autopsied patients with bronchogenic carcinoma without clinical renal disease were studied by electron microscopy and immuno-histochemistry for the presence of glomerular deposits. Two patients had subepithelial electron-dense deposits compatible with immune complexes but failed to stain histochemically for immunoglobu-lin; most cases (19 of 27). including the two with complexes, demonstrated subendothelial deposition of fibrin. No tissue samples had histochemically detectable immunoglobulin. From this study it is suggested that renal immune complexes in lung cancer are rare.     

Warty Carcinoma Arising in Condyloma Acuminatum of Urinary Bladder: A Case Report

We describe the case of a 62-year-old man with chronic irritation of the urinary bladder resulting in dysuria and hypogastric pain. Three neoplasms measuring 0.5, 1, and 1.5 cm, respectively, were observed by cystoscopy and removed by transurethral resection (TUR). Histologic examination showed a complex folding of squamous hyperplastic epithelium around a connective tissue core. The superficial epithelium contained numerous koilocytes. The double polymerase chain reaction (PCR) detected DNA of type 11 human papillomavirus (HPV). The diagnosis was condyloma acuminatum of bladder. Three months later the patient presented with fever, and a new cytoscopy demonstrated an ulcerated, exophytic 4.5 cm mass. Histopathology showed a squamous carcinoma with papillomatous structure, pronounced viral koilocytosis, and irregular invasive deep margin. HPV type 11 was found with double PCR. The diagnosis was warty carcinoma arising in condyloma acuminatum. To the best of our knowledge, this is the first case of warty carcinoma of the urinary bladder described in the literature. We discuss the relationship between the infection by HPV and the development of condyloma acuminatum, its evolution toward a well-differentiated squamous carcinoma, and its distinction from verrucous carcinoma. Int J Surg Pathol 8(3):253-259, 2000     

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。