[Apropos of 1 case of paratesticular papillary serous cystadenocarcinoma]. / A propos d'un cas de cystadénocarcinome papillaire séreux paratesticulaire.

The occurrence within the testis or paratesticular tissue of serous tumors, similar to ovarian tumors, is rare. This article reports a primary serous paratesticular cystadenocarcinoma in a 39 year-old man. From data of the literature, we offer guidelines for diagnosis, histogenesis and treatment of this rare tumor.

Angiogenesis of liver metastases: role of sinusoidal endothelial cells.

PURPOSE: Tumor-induced angiogenesis requires migration and remodeling of endothelial cells derived from pre-existing blood vessels. Vascular endothelial growth factor is the growth factor most closely implicated in the development of neovessels in colon cancer. However, vascular endothelial growth factor-specific receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels surrounding vascular endothelial growth factor-producing secondary hepatic tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism of neovessel formation within liver metastatic carcinomas remains unclear. The purpose of this study was to determine whether sinusoidal endothelial cells are involved in tumor angiogenesis in a syngeneic model of liver metastases from colorectal cancer. METHODS: Sinusoidal endothelial cells were identified by fluorescence microscopy after uptake of acetylated low density lipoprotein labeled with a fluorescent probe (dioctadecylindocarbocyanine). One hundred microliters of dioctadecylindocarbocyanine acetylated low density lipoprotein were injected intraportally at the start of experiment in BD IX rats. Two days later, intraportal injection of 10(7) DHD K12, a chemically induced colon carcinoma cell line, was performed in syngeneic BD IX rats. Animals were killed one week later and the livers were processed for routine histologic examination and immunohistochemistry using the rat endothelial cell antigen-1 monoclonal antibody. RESULTS: In normal parenchyma fluorescence was associated with sinusoidal cells but not with endothelium of large blood vessels. Thus, specific acetylated low density lipoprotein uptake allowed histological differentiation of sinusoidal endothelial cells from other large-vessel endothelial cells present in the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence was generated. Labeled cells accumulated at the periphery of the metastases. When tumors grow beyond 200 microm, neovessel formation was observed; there was an invasion of fluorescent-labeled cells from the periphery, which were arranged in a tubular formation within neoplasia. CONCLUSION: In liver metastases tumor vessels are lined with sinusoidal endothelial cells. Identification of a specific cell type involved in the formation of the stromal compartment of tumors has important implications. Sinusoidal endothelial cells express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. They should be considered as attractive targets for future and existing antiangiogenic strategies directed against the stromal compartment of liver metastases.

[Adrenal medullary hyperplasia: a rare etiology of arterial hypertension--report of a case]. / L'hyperplasie médullosurrénalienne: une étiologie rare de l'hypertension artérielle--rapport d'un cas.

Adrenal medullary hyperplasia is often misdiagnosed. The clinical features may resemble those of pheochromocytoma, with paroxysmal hypertension and elevated urinary catecholamine and metanephrine levels. Pathologic study shows diffuse or nodular adrenal medullary hyperplasia, determined by morphometric analysis: increased adrenal gland weight, increased relative medullary volume, increased relative medullary weight, decreased cortico-medullary ratio. Adrenal medullary hyperplasia may be primary or sporadic, but is often associated with multiple endocrine neoplasia (MEN) type II.

[Presacral myelolipoma]. / Myélolipome présacré.

Presacral myelolipoma is a rare benign tumour of unknown aetiology, composed of mature adipose tissue with intermixed normal haematopoietic cells. Computed tomography is of help in the diagnosis but biopsy is mandatory in order to avoid unnecessary surgery. A case is reported.

[Congenital hepatic fibrosis. Five cases with late occurrence in adults]. / Fibrose hépatique congénitale. Cinq cas à révélation tardive chez l'adulte.

Congenital hepatic fibrosis (CHF), is an autosomal recessive disease, presenting principally in childhood with portal hypertension and/or cholangitis, and often associated with renal malformations. The forms presenting later in adults are rare, and illustrated herein by 4 cases with dominant cholangitis, and one latent form. Biological tests and radiological imaging are often normal. The histopathologic diagnosis, sometimes difficult on liver needle biopsy is based on fibrous enlargement of portal areas, with numerous and tortuous bile ducts, lined by regular, cuboidal epithelium. Interportal fibrosis can mimic cirrhosis. In CHF, cholangitis are favoured by intrahepatic biliary dilatation, sometimes related to Caroli's disease, associated in 25% of cases. Suppurative complications, sometimes fatal explain the severity of cholangitis forms of CHF, contraindicating inopportune cholangiography and biliary surgery.

DNA ploidy by image cytometry in urothelial carcinomas. Comparison of touch imprints and paraffin-embedded biopsies from 31 patients.

OBJECTIVE: To compare DNA content measured by image cytometry from touch imprints and formalinfixed, paraffin-embedded samples in bladder carcinomas. STUDY DESIGN: Thirty-one biopsies of urothelial carcinomas were selected for a prospective study. Imprints of fresh specimens were performed. Cell suspensions were obtained from dewaxed samples by the procedure of Hedley. Sections 7 microns thick were used for carcinoma in situ and small biopsies. The DNA ploidy index was measured on Feulgen-stained slides using an image cytometer. RESULTS: From imprint analysis, seven grade 1 carcinomas (n = 9) were found to be diploid (78%). Nine grade 2 carcinomas (n = 12) exhibited aneuploidy (75%), as did all grade 3 and in situ carcinomas (n = 10). Multiploidy was demonstrated from imprints in four cases instead of the two detected from dewaxed tissue. In 27 cases (87%), G0/G1 peaks obtained from paraffin blocks showed a shift to the left. In five cases (16%), variations in the DNA index were responsible for discrepancies in the DNA ploidy evaluation between fresh imprints and dewaxed samples of the same tumors. CONCLUSION: Image cytometry on Feulgen-stained imprints of bladder biopsies is a simple and reliable procedure for assessing DNA ploidy in urothelial carcinomas, providing great sensitivity for detecting small aneuploid peaks and multiploid tumors. DNA image analysis of touch preparations is especially useful for carcinoma in situ and small biopsies unsuitable for Hedley's technique.

[Adenomatoid tumors of the uterus. Study of 5 cases with immunohistochemical and ultrastructural confirmation of the mesothelial origin]. / Tumeurs adénomatoïdes de l'utérus. Etude de cinq cas avec confirmation immunohistochimique et ultrastructurale de l'origine mésothéliale.

Five cases of adenomatoid tumors of the uterus (ATU) are reported. These benign lesions are discovered in 1% of the hysterectomy specimens, performed on 20- to 85-years-old women. Their frequency is certainly underestimated, since ATU have the same macroscopic appearance as leiomyomas. Histologically, ATU are formed by gland-like and pseudovascular lumens, lined by regular, cuboidal or flattened cells, and surrounded by hyperplastic smooth muscle bundles. Immunohistochemical coexpression of cytokeratin and vimentin confirms with a mesothelial histogenesis. The ultrastructural study, showing luminal microvilli and desmosomes supports the hamartomatous development of ATU, corresponding to mesothelial inclusions from the peritoneum into the myometrium. Some giant or diffuse ATU, which are clinically disturbing, are differentiated from carcinomatous or vascular proliferations by frozen section examination. The treatment is made by surgical excision.

Bacillary angiomatosis in HIV-infected patients: report of three cases with different clinical courses and identification of Rochalimaea quintana as the aetiological agent.

Three cases of cutaneous bacillary angiomatosis in HIV-infected patients are reported. They differed profoundly with respect to the extent of the lesions and the clinical course. In two cases, Rochalimaea quintana was identified by direct sequencing of the DNA amplified with the polymerase chain reaction (PCR), whereas an easy, rapid method based on the restriction length of polymorphism analysis of PCR products (PCR-RFLP) was used in the third case. This report illustrates the variations in clinical presentations and evolutive profiles in patients with bacillary angiomatosis, and confirms the causal role of R. quintana in this disease.

[Colonic Histoplasma capsulatum pseudotumor in AIDS. Morphological and immunohistochemical diagnosis of an isolated lesion]. / Pseudotumeur colique à Histoplasma capsulatum au cours du SIDA. Diagnostic morphologique et immunohistochimique d'une lésion isolée.

The authors report a case of a 35-year-old man with acquired immunodeficiency syndrome (AIDS) and a left colonic mass with Histoplasma capsulatum (H. capsulatum). The look-up performed looking for disseminated infection was negative. In the absence of positive cultures, the diagnosis was determined morphologically based on the presence of yeast observed by light and electron microscopy. The diagnosis was also verified by positive immunofluorescence using specific anti-Histoplasma antibodies. Gastrointestinal histoplasmosis is a frequent complication of AIDS, particularly in some endemic areas of America. Association with a disseminated mycotic infection is then common. Histoplasmosis is less frequently diagnosed in Europe and isolated involvement of the colon is exceptional. When the mycological study is not performed or is negative, only morphological and immunohistochemical methods are able to establish the diagnosis and eliminate other mycotic diseases occurring during AIDS.

Thyroid spindle epithelial tumor with thymus-like differentiation (the "SETTLE" tumor). An immunohistochemical and electron microscopic study.

An intrathyroid primary epithelial spindle-cell tumor with mucous cysts is described in a 9-year-old child. Histologically, this well-circumscribed tumor exhibited a nodular pattern, a prominent spindle cell component with minimal pleomorphism, and well-differentiated mucinous glands within fibrous bands. The spindle cells demonstrated diffuse immunopositivity for cytokeratin and vimentin. Electron microscopy of tissue sections demonstrated that cells contained bundles of cytoplasmic tonofilaments and numerous desmosomes. The light and electron microscopic features and immunohistochemical profile of this tumor were similar to those of recently described thyroid tumors that have been called "SETTLE" tumors (i.e., spindle epithelial tumor with thymus-like differentiation). These uncommon tumors can be considered intrathyroid thymoblastomas and must be regarded as potentially malignant lesions.

Proliferative responses of epithelial cells to 8-bromo-cyclic AMP and to a phorbol ester change during breast pathogenesis.

We have explored the relationship of changes in proliferative responses of human mammary epithelial cells to a phorbol ester (TPA) and to 8-Br-cAMP, which modulate the activities of protein kinases A and C (PKA and PKC), with breast tumour progression. Treatment with TPA had no effect on nontumorigenic cell lines established from human fibrocystic biopsies and apparently normal tissue around a tumour. In contrast, TPA strongly inhibited the proliferation of numerous human tumorigenic breast cell lines. Treatment with 8-Br-cAMP decreased the proliferation of all studied nontumorigenic and tumorigenic cell lines. We have also studied the effect of TPA and 8-Br-cAMP on growth of epithelial cells in short-term culture obtained from surgical human mammary biopsies with different states of breast disease. Both drugs enhanced growth of normal breast cells but had no significant effects on cells from biopsies with benign breast disease. In contrast, all examined cultures from breast cancer biopsies were strongly inhibited by 8-Br-cAMP. Otherwise, TPA had an inhibitory effect only in the case of invasive ductal carcinoma of grade III. Malignant Ha-ras-transformation of nontumorigenic TPA-insensitive breast HBL-100 cells induced an inhibitory effect of TPA. In addition, a TPA-insensitive MCF7 clone was much less tumorigenic in athymic mice than the parental strain shown to be inhibited by TPA. These data suggest that the two intracellular transduction pathways change at different stages of breast pathogenesis. Alterations in the PKA pathway are early events and are probably important to cell immortalization but do not necessarily lead to malignant development. In contrast, changes in PKC pathway are rather later events associated with advanced malignant transformation.

Fibroblast-mediated differentiation in human breast carcinoma cells (MCF-7) grown as nodules in vitro.

The growth of cells in 3-dimensional form as nodules in vitro facilitates studies of in vivo cellular interactions. Taking advantage of this technique, human breast carcinoma cells (MCF-7) were co-cultured with stromal fibroblasts isolated from either normal or tumorous breast tissue to study the influence of such fibroblasts on tumor-cell growth and differentiation. Ten days after co-culture of carcinoma cells with fibroblasts from normal tissue at a 1:10 ratio, the size of nodules began to increase and stabilize by day 30 while the fibroblast number decreased and finally disappeared. Concurrently, the carcinoma cells underwent a progressive redifferentiation process which histologically resulted in the appearance of highly developed papillar and tubular structures after 2 months in culture. The production of mucins was further evidence that these cells had undergone differentiation. By contrast, when MCF-7 cells were grown alone or with fibroblasts isolated from a breast carcinoma, the nodules continued to exhibit their characteristic histodedifferentiation properties and did not grow. The re-establishment of a normal epithelial state of differentiation in MCF-7 carcinoma nodules indicates that the phenotypic characteristics of tumor cells are reversible and are influenced or controlled by the stromal environment by which these tumor cells are surrounded or in contact with. Overall, our results open the possibility of exploiting the effects that connective tissue cells have on tumor-cell differentiation for use in prevention and treatment of cancer.

Lymphokine-activated killer cells induce differentiation in MCF-7 breast carcinoma nodules but not in mastosis nodules maintained in three-dimensional culture.

In order to better understand the interaction between activated lymphocytes and breast carcinoma cells, we studied the degree of infiltration, the membrane contacts established and their cytostatic and cytolytic effects in MCF-7 nodules maintained in three-dimensional culture. A comparison was made with nodules of a nonmalignant, immortalized mastosis cell line. Histological, immunohistochemical and electron microscopical observations were performed as well as DNA synthesis measurements in the two components of the coculture. The lymphokine-activated killer (LAK) cells adhered more frequently to the carcinoma nodules than to the mastosis nodules. They actively penetrated into both of them. The penetration remained peripheral, and only a few cells migrated more deeply. The LAK cells established close cell-to-cell contacts with the two types of nodules, and intercellular gaps were formed: damaged cells could be seen near the activated killer cells. In MCF-7 nodules, a 5-fold inhibition of proliferation occurred, and extensive necrotic zones developed; this was accompanied by a general tendency for glandular redifferentiation. In mastosis nodules, necrosis also developed but no cell differentiation occurred and proliferation was less inhibited (2 times). Interleukin-2 alone enhanced DNA synthesis in mastosis nodules but had no effect on MCF-7 nodules, and no extending necrosis could be seen in both types of nodules. The cytolytic effects of LAK cells combined with their redifferentiating effect in MCF-7 breast carcinoma nodules may be a useful indication for further breast cancer therapy research.