Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas

Intracytoplasmic mucinous inclusions and lumina have been previously described in non-glandular neoplasms such as urothelial carcinoma. We describe their presence in 93% of non-mucinous ovarian carcinomas. They were found in abundance in all 25 cases (100%) of clear cell carcinoma, in 48 of 50 cases (96%) of serous carcinoma and 20 of 25 cases (80%) of endometrioid carcinoma. The degree of the differentiation of the tumour did not influence the number of inclusions or lumina observed. These results suggest that the presence of intracytoplasmic lumina and mucinous inclusions is more widespread than hitherto appreciated. Their presence in an otherwise poorly differentiated metastatic carcinoma might, at the very least, prompt one to consider the ovary as a possible primary site. In addition, an abundance of intracytoplasmic mucinous inclusions and lumina with microcyst formation, in an otherwise poorly differentiated malignant primary ovarian epithelial tumour, might suggest the possibility of a clear cell carcinoma.     

Intracytoplasmic lumina in invasive micropapillary carcinoma of the lung

Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3-20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site.     

Intracytoplasmic lumina in breast carcinoma: a helpful histopathologic feature.

Eelectron microscopy has disclosed the presence of intracytoplasmic lumina within breast cancer cells. These structures can be recognized with the light microscope by their sharp, round outlines and thick walls. Their identification in large numbers may provide additional support for the breast origin of a metastatic tumor. Three illustrative cases in which demonstration of intracytoplasmic lumina was diagnostically helpful are presented.     

Intracytoplasmic lumina of human breast cancer--a microscopic study and practical application in cytological diagnosis

Intracytoplasmic lumina (ICLs) of breast carcinoma cells are dominantly noted as rather specific structures in various organella of carcinoma cells. The present study deals with the characteristic patterns of ICLs in the ultrastructural and cytological features of breast carcinomas. Ultrastructural analysis of benign and malignant breast lesions for ICLs revealed a high occurrence of such lumina in the carcinomas. Especially the lumina were frequently noted in cells of scirrhous carcinomas (scirrhous carcinoma: 42 ICLs, medullary tubular carcinoma: 24, papillotubular carcinoma: 17 per each 300 carcinoma cells, mastopathy: 7 ICLs, fibroadenoma: 3, normal mammary gland: 1 or 2 per each epithelial cell). In 55.6% of the cytological cases of scirrhous carcinoma, the tumor cells showed ICLs, whereas such lumina were found at a rate of only 3.4% in benign lesions. These results demonstrate that the detection of ICLs by cytological examination can be useful in the establishment of a diagnosis of scirrhous carcinoma, and in the decision on a breast origin for metastatic tumors.     

Intracytoplasmic and extracytoplasmic lumina with a peripheral halo and spikes (spicular bodies) found in epithelial tumors

Intracytoplasmic lumina, each with a peripheral halo and spikes, a hitherto undescribed histological structure, were found in several human carcinomas. Similar structures found at the free surfaces of carcinoma cells, or those composed of several individual carcinoma cells, were designated extracytoplasmic lumina with a peripheral halo and spikes. Haloes were seen along the cytoplasm around the lumina, and the spikes penetrated into the cytoplasmic haloes. Transmission electron microscopy revealed that these spicular bodies were lumina equipped with microvilli containing an actin core. Spicular bodies were found in the following neoplasms; 22% of hepatocellular carcinomas (11/50), 35% of colonic adenocarcinomas (7/20), 31% of gastric adenocarcinomas (16/51). In contrast, no or only very occasional spicular bodies were found in thyroid (0/20) and mammary (1/22) adenocarcinomas. Although the diagnostic value of this structure is unknown at the present time, its identification in a carcinoma may be a histologic indicator of its endodermal nature.     

Intraepithelial lumina in urothelial bladder neoplasms. A histochemical, immunohistochemical and electron microscopy study

Intraepithelial lumina observed in 12 urothelial bladder neoplasms were studied histochemically, immunohistochemically and ultrastructurally. Both intercellular and intracytoplasmic lumina could be demonstrated showing an alcianophilic margin and containing non-sulphated acid mucins. The presence of secretory component (SC) was identified in neoplastic urothelial cells around or adjacent to intercellular lumina as well as in cells with intracytoplasmic lumina. The cells surrounding intercellular lumina revealed ultrastructurally tight junctions, microvilli and a prominent glycocalyx while cellular remnants were found quite often within the lumen. As similar histochemical, immunohistochemical and ultrastructural characteristics are also expressed in surface umbrella cells of normal urothelium it is suggested that a focal differentiation of neoplastic urothelial cells towards surface umbrella-like cells takes place and that this process is intimately related to the formation of lumina.     

HLA class I expression in bladder carcinomas

HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.     

Cytogenetic investigation on 30 bladder carcinomas

Cytogenetic study of 30 bladder carcinomas confirmed the heterogeneity and the complexity of the karyotypic picture in this type of tumor. Presence of numerical and/or structural chromosome aberrations was observed in all tumors. Clonal abnormalities were found in 19 cases. Chromosomes most frequently involved in changes were chromosome #1, #3 and #11(36.6%, 26.6%, and 20% of the cases respectively). Trisomy 7 and monosomy 9 were the sole abnormalities in one case each.     

Non‐urothelial carcinomas of the bladder

Non‐urothelial carcinomas involving the bladder are uncommon and often diagnostically challenging. These carcinomas may show squamous, adenocarcinomatous or neuroendocrine features, with immunohistochemical stains aiding the diagnosis in only a subset of cases. The clinical history in non‐urothelial bladder carcinomas is important, given that the differential diagnosis often includes secondary involvement of the bladder by direct extension or metastasis from carcinomas at other sites. This paper will review non‐urothelial carcinomas in each of these three morphological categories, emphasising recent changes in diagnostic grouping and challenges in the histopathological diagnosis. Review of bladder cancers with squamous morphology will include discussion of conventional squamous cell carcinoma and verrucous carcinoma and their distinction from urothelial carcinoma with extensive squamous differentiation. Bladder carcinomas with adenocarcinomatous change will include primary bladder adenocarcinoma, urachal adenocarcinoma and tumours of Müllerian type. Finally, neuroendocrine neoplasms of the bladder, including well‐differentiated neuroendocrine tumour and neuroendocrine carcinomas, will be discussed. Associated surface findings, risk factors and prognostic features will be described.     

Karyotypic characterization of urinary bladder transitional cell carcinomas

Samples from 34 primary transitional cell carcinomas (TCCs) of the bladder were short-term-cultured and processed for cytogenetic analysis after G-banding of the chromosomes. Clonal chromosome abnormalities were detected in 27 tumors and normal karyotypes in 3, and the cultures from 4 tumors failed to grow. Losses of genetic material were more common than gains, indicating that loss of tumor suppressor genes may be of major importance in TCC pathogenesis. There was no clonal heterogeneity within individual tumors, consonant with the view that TCCs are monoclonal in origin. The most striking finding was the involvement of chromosome 9 in 92% of the informative cases, as numerical loss of one chromosome copy in 15 cases, but as structural rearrangement in 8. The changes in chromosome 9 always led to loss of material; from 9p, from 9q, or of the entire chromosome. A total of 16 recurrent, unbalanced structural rearrangements were seen, of which del(1)(p11), add(3)(q21), add(5)(q11), del(6)(q13), add(7)(q11), add(11)(p11), i(13)(q10), del(14)(q24), and i(17)(q10) are described here for the first time. The karyotypic imbalances were dominated by losses of the entire or parts of chromosome arms 1p, 9p, 9q, 11p, 13p, and 17p, loss of an entire copy of chromosomes 9, 14, 16, 18, and the Y chromosome, and gains of chromosome arms 1q and 13q and of chromosomes 7 and 20. The chromosome bands and centomeric breakpoints preferentially involved in structural rearrangements were 1q12, 2q11, 5q11, 8q24, 9p13, 9q13, 9q22, 11p11, and 13p10. Rearrangements of 17p and the formation of an i(5)(p10) were associated with more aggressive tumor phenotypes. There was also a general correlation between the tumors' grade/stage and karyotypic complexity, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis.     

Cytogenetic analysis of 62 transitional cell bladder carcinomas

Chromosome analysis of biopsy material obtained after vinblastine pretreatment was carried out in 108 specimens from 89 patients with transitional cell carcinoma of the urinary bladder. Analyzable metaphases were obtained in 62 tumors, but only in nine tumors could karyotypes be analyzed by banding; a conventional technique was used in all others. Ploidy and occurrence of markers corresponded with tumor morphology and invasion and sometimes aided in the clinical evaluation; chromosome anomalies specific for bladder cancer were not revealed. In noninvasive tumors of WHO grade 1 and 2, near-diploid karyotypes with occasional marker chromosomes dominated. Grade 3 tumors showed a variety of grossly aneuploid karyotypes, with an almost constant occurrence of different markers. Superficially invasive G2 tumors had moderately pronounced aberrations with more deviations than noninvasive tumors but without the great variety of G3 tumors.     

Comparative study of urinary bladder carcinomas in Japanese and Egyptians

One hundred six Japanese and 169 Egyptian cases of urinary bladder carcinoma treated by total cystectomy were analyzed histopathologically. Urinary bladder carcinomas in Egypt were encountered at an earlier age than those in Japan. The proportion of carcinomas in Egyptian males was higher than in Japanese males. Squamous cell carcinomas (SCCs) predominated in Egyptian cases whereas transitional cell carcinomas predominated in Japanese cases. The pathological stage of Egyptian cancers was more advanced than in Japanese cases; even grade 1 SCCs showed invasion into the muscular layer. Most carcinomas in Egypt were associated with Schistosoma haematobium infections.     

膀胱癌的性激素受体检测及其意义

应用免疫酶标ＡＢＣ法，对９３例膀胱移行细胞癌进行雌激素受体（ＥＲ）、孕激素受体（ＰＲ）及雄激素受体（ＡＲ）检测。结果：膀胱癌的ＥＲ、ＰＲ及ＡＲ阳性率分别为４０．０９％、５２．６８％及５２．６８％，说明膀胱癌与性激素有一定关系，ＡＲ阳性例中多发性癌较高，ＥＲ阳性例复发率低，提示抗性激素内分泌辅助治疗，对部分膀胱癌可能有效，并对预测预后有一定意义。     

Chromosomal imbalances in small cell carcinomas of the urinary bladder.

Small cell carcinomas (SCCs) represent a rare histological subtype of urinary bladder cancer. Little is known abut the genetic alterations in these tumours. To identify chromosomal aberrations that are typically present in SCC of the urinary bladder, ten tumours were analysed by comparative genomic hybridization (CGH). CGH allows screening for all relative DNA copy number gains and losses present in a tumour. SCCs of the bladder were characterized by a high number of genomic alterations (mean: 11.3 per tumour). Deletions were most frequent at 10q (7 of 10 tumours deleted), 4q, 5q (5/10 each), and 13q (4/10). These regions may carry tumour suppressor genes with relevance for this particular tumour type. Gains of DNA sequences were most prevalent at 8q (5/10), 5p, 6p, and 20q (4/10 each). High level amplifications were found at 1p22-32, 3q26.3, 8q24, and 12q14-21. These loci may pinpoint the localization of oncogenes with relevance for small cell bladder cancer. The analysis of one tumour having areas of both SCC and transitional cell carcinoma strongly suggests that SCC can develop from TCC through the acquisition of additional genetic alterations.