Distribution of silver-stained interphase nucleolar organizer regions as a parameter to distinguish neoplastic from nonneoplastic reactive cells in human effusions.

The distribution of interphasic nucleolar organizer regions (NORs) was studied in cytologic preparations of human serous effusions in order to differentiate malignant cells from nonmalignant reactive cells. The study was carried out on 80 cases of metastatic adenocarcinoma, 10 cases of mesothelioma, 10 reactive pleural effusions and 5 peritoneal washings. Visualization of NORs at the light microscopic level was obtained using a silver-staining technique for acidic proteins selectively associated with NORs. The morphologic data were also statistically evaluated by means of an automated image analyzer. The quantity of silver-stained NORs was higher in cancer cells (both mesothelioma and adenocarcinoma) than in reactive mesothelial cells. Moreover, NORs were more irregularly distributed within the nucleoli and were more variably sized in cancer cells than in reactive mesothelial cells.

Morphometric evaluation of microvessels surrounding hyperplastic and neoplastic mammary lesions.

Size and density of microvessels in close proximity to normal, hyperplastic, and in situ neoplastic mammary epithelium were evaluated with a morphometric method. Human tissue samples were obtained from breast mammoplasty or biopsy specimens with diagnosis of either epitheliosis or ductal carcinoma in situ. The mean vessel size was significantly enhanced in hyperplastic and neoplastic lesions as compared to mammoplasty specimens considered as 'normal'. On the contrary, the density of the microvessels around the epithelium was comparable in the three groups of tissues. It appears that as long as the basement membrane remains intact, sprouting of new vessels around neoplastic lesions is not manifested.

Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro.

We report here that rings of rat aorta embedded in gels of fibrin or collagen and cultured in MCDB 131, an optimized growth medium for microvascular endothelial cells, generate branching microvessels in the absence of serum or other soluble protein supplements. The angiogenic response is self-limited and can be quantitated by counting the newly formed microvessels daily in the living cultures. The microvascular growth curves are characteristic for each gel. Growth of microvessels in collagen gel peaks at the end of the 1st week and is followed by a rapid regression in the 2nd week. Fibrin gels, as compared with collagen, stimulate angiogenesis by 170%, support growth during the 2nd week, and protect the newly formed microvessels from early regression. Angiogenesis is inhibited by adding hydrocortisone to the culture medium. Conversely, a 230% stimulation of angiogenesis is obtained when aortic rings are cultured in collagen gels floating in serum-free medium conditioned by sarcoma 180 cells. Our results demonstrate that: (a) angiogenesis can be obtained reproducibly in serum-free culture; (b) serum-free culture is a sensitive method for testing the inhibitory or stimulatory effects of soluble or matrix factors on angiogenesis; (c) the aortic ring model can be used as a quantitative assay for the study of angiogenesis under chemically defined culture conditions.

Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot.

Rings of rat aorta cultured in Matrigel, a reconstituted gel composed of basement membrane molecules, gave rise to three-dimensional networks composed of solid cellular cords and occasional microvessels with slitlike lumina. Immunohistochemical and ultrastructural studies showed that the solid cords were composed of endothelial sprouts surrounded by nonendothelial mesenchymal cells. The angiogenic response of the aortic rings in Matrigel was compared to that obtained in interstitial collagen, fibrin, or plasma clot. Morphometric analysis demonstrated that the mean luminal area of the microvascular sprouts and channels was significantly smaller in Matrigel than in collagen, fibrin, or plasma clot. The percentage of patent microvessels in Matrigel was also markedly reduced. Autoradiographic studies of 3H-thymidine-labeled cultures showed reduced DNA synthesis by developing microvessels in Matrigel. The overall number of solid endothelial cords and microvessels was lower in Matrigel than in fibrin or plasma clot. A mixed cell population isolated from Matrigel cultures formed a monolayer in collagen or fibrin-coated dishes but rapidly reorganized into a polygonal network when plated on Matrigel. The observation that gels composed of basement membrane molecules modulate the canalization, proliferation, and organization into networks of vasoformative endothelial cells in three-dimensional cultures supports the hypothesis that the basement membrane is a potent regulator of microvascular growth and morphogenesis.

[Aids-related cerebral lymphoma. Pathologic and immunohistochemical study of 19 cases]. / Linfomi cerebrali AIDS-correlati. Studio patologico ed immunoistochimico di 19 casi.

We studied 19 cases of AIDS-related cerebral lymphomas, 15 of which are primary, and 4 secondary to systemic lymphoma. Eighteen cases are classified as non-Hodgkin's B cell lymphomas; in 1 case, an anaplastic large cell lymphoma coexists with systemic Hodgkin's disease. High-grade histologic types predominate (centroblastic, immunoblastic and immunoblastic plasmocytoid). One case of angiotropic lymphoma is included solely localized to the brain. We describe clinical and radiological features, gross, microscopic and immunophenotypic appearances. Other HIV-related associated diseases of the central nervous system are also considered.

Dual secretory and myoepithelial differentiation in the transplantable R3230AC rat mammary carcinoma.

The hormone-responsive R3230AC mammary carcinoma, serially transplantable in Fisher rats, shows striking functional and morphological similarities to the normal mammary gland. We have studied its cellular composition by both light and electron microscopy, employing markers of myoepithelial and epithelial cells. We identified two cell types: the major cellular component corresponded to epithelial milk-protein secreting cells, while a second component showed immunocytochemical and ultrastructural characteristics of the myoepithelial cells. These cells were positive with a monoclonal antibody detecting alpha smooth muscle actin. The dual differentiation which normally occurs in breast ducts is therefore reproduced in a malignant experimental tumor. The coexistence of neoplastic cell populations, divergent in morphology and function, that persist in a tumor despite many transplant generations, leads to reconsideration of the relationship between cellular differentiation and malignant transformation.

[Multiple Spitz nevus]. / Nevo di Spitz multiplo.

Benign juvenile melanoma was originally described and differentiated from malignant melanoma by Sophie Spitz in 1948. The solitary form is the most frequent and usually appears on the face and extremities of young children and adolescents as a solitary, hairless, dome-shaped papule or nodule, varying in size from 3 to 15 mm. It can be of a wide spectrum of colors including pink, yellow, red, brown, purple and black, representing 1% to 8% of melanocytic tumors in children. Histologically, Spitz nevus has been subdivided into junctional, compound and intradermal type according to the location of neoplastic melanocytes in the skin. Rarely multiple benign juvenile melanoma arranged in clusters (agminated) or widespread (disseminated) are described. Less than 50 cases have been reported in the world literature. The grouped form usually occurs on the face of children on normal, but also hyperpigmented or hypopigmented skin, while the disseminated one in adults. A case of multiple agminated Spitz nevus arised on the face of a 2 years old girl is reported. The clinical presentations with a 3 years follow-up and the histologic features of this nevus are described as well as the therapeutic approach.

Cutaneous metastasis of neuroendocrine carcinoma of the larynx: report of a case.

BACKGROUND: Cutaneous metastasis from neuroendocrine carcinomas of visceral origin is rarely described in indexed literature. The primary sites of origin include: lung (Wick et al., J Am Acad Dermatol 1985; 13: 134), larynx (Zambruno et al., Ann Dermatol Venereol 1989; 116: 855; Schmidt et al., J Laryngol Otol 1994; 108: 272; Guerzider et al., Ann Pathol 1991; 11 (4): 253), mediastinum (Yoshimasu et al., J Dermatol 2001; 28 (3): 168), uterus (Fogaca et al., J Cutan Pathol 1993; 20: 455), and thymus (Wick et al., J Am Acad Dermatol 1985; 13: 134). METHODS: In this report, the authors present the clinical, histological, immunohistochemical, and ultrastructural characteristics of secondary skin localizations of a neuroendocrine laryngeal tumor that occurred in a 61-year-old man. The complete follow up of the case is described and a brief revision of the terminology and classification of neuroendocrine neoplasms of the larynx is discussed, since a significant relationship exists between the degree of differentiation and biological behavior. RESULTS: On histological examination, the secondary cutaneous localization appeared to be more dedifferentiated compared to the primary tumor. The immunohistochemical patterns of reactivity were similar in both neoplasms, showing expression of neuroendocrine and epithelial markers. CONCLUSIONS: An important issue of prognostic significance is to differentiate a cutaneous metastasis of a neuroendocrine carcinoma from the primary small cell-undifferentiated carcinoma of the skin (Merkel cell carcinoma).