Angelo A. Ucci

The stroma as a crucial target in rat mammary gland carcinogenesis

A complex network of interactions between the stroma, the extracellular matrix and the epithelium drives mammary gland development and function. Two main assumptions in chemical carcinogenesis of the mammary gland have been that carcinogens induce neoplasia by causing mutations in the DNA of the epithelial cells and that the alterations of tissue architecture observed in neoplasms are a consequence of this primary mutational event. Here, we use a rat mammary tissue recombination model and the chemical carcinogen N-nitrosomethylurea (NMU) to determine whether the primary target of the carcinogen is the epithelium, the stroma or both tissue compartments. Mammary epithelial cells were exposed in vitro either to the carcinogen or vehicle before being transplanted into the cleared fat pads of rats exposed to carcinogen or vehicle. We observed that neoplastic transformation of these mammary epithelial cells occurred only when the stroma was exposed in vivo to NMU, regardless of whether or not the epithelial cells were exposed to the carcinogen. Mammary epithelial cells exposed in vitro to the carcinogen formed phenotypically normal ducts when injected into a non-treated stroma. Mutation in the Ha-ras-1 gene did not correlate with initiation of neoplasia. Not only was it often found in both cleared mammary fat pads of vehicle-treated animals and intact mammary glands of untreated animals, but it was also absent in some tumors. Our results suggest that the stroma is a crucial target of the carcinogen and that mutation in the Ha-ras-1 gene is neither necessary nor sufficient for tumor initiation.

Malignant lymphoma and malignant angioendotheliomatosis: One disease

A patient was diagnosed as having angioendotheliomatosis proliferans systemisata (APS) based on characteristic clinical and histologic features. A few days later, malignant lymphoma involving the gut was discovered. Immunohistochemical and electronmicroscopic studies confirmed the nonendothelial and lymphoid nature of intravascular tumor cells. This is the sixth case in which malignant lymphoma has been shown to involve the vessels of the skin (and probably of other organs) in a pattern identical to that seen in APS.

Vesiculobullous lesions caused by cytomegalovirus infection in an immunocompromised adult

Skin involvement in cytomegalovirus (CMV) infection is very rare. Reported cutaneous manifestations are nonspecific and include petechial, purpuric, and morbilliform rashes. We describe an immunocompromised patient who developed a vesiculobullous eruption. A simple Tzanck preparation from the base of a blister revealed multinucleate giant cells suggestive of a viral infection. Subsequent viral cultures and electron microscopic studies confirmed the diagnosis of CMV infection. Consideration of this infection should be included in the differential diagnosis of multinucleate giant cells seen on Tzanck preparations of cutaneous vesicles.

Multifocal pigmentation of prostatic and bladder urothelium.

Multifocal pigmentation of the bladder and prostatic urothelium is described in 2 white men. The light microscopic, electron microscopic and histochemical characterization of these foci identified the contained pigment as melanin.

Histological analysis of low dose NMU effects in the rat mammary gland.

BackgroundOur objective was to assess the histological changes in mammary glands of the female Wistar-Furth rat as a result of low dose exposure to N-nitrosomethylurea (NMU).MethodsGroups of 30–40 virgin female rats of between 49–58 days old received a single injection of 10, 20, 30 or 50 mg NMU/kg body weight (BW). A group of 10 control rats received 0.9% NaCl solution only. The formation of palpable mammary gland tumors was assessed weekly and, upon sacrifice at 12, 22 and 25–30 weeks after treatment, we performed a comprehensive histological analysis of all mammary gland lesions and tumors.ResultsAlongside the predicted increase in tumor number and decrease in tumor latency with increasing NMU dose, we observed a number of microscopic lesions and other epithelial abnormalities in the mammary glands for all NMU doses. Two types of non-neoplastic histological changes were observed in rats exposed to 10 or 20 mg NMU/kg BW: namely, (i) an increase in the number of acinar structures often accompanied by secretion into the lumen which is normally associated with pregnancy and lactation, and (ii) an increase in the number of epithelial cells sloughed into the lumen of the epithelial ducts.ConclusionThis study establishes a baseline for low-dose exposure and defines the histological features in the mammary gland resulting from NMU exposure. Furthermore, this system provides an ideal platform for evaluating the relative susceptibility of animals protected from, or predisposed to, developing cancer through environmental influences.

Diagnostic utility of CD10, CD3 and electron microscopy of renal cortical neoplasms with oncocytic features.

No currently defined imaging techniques can reliably distinguish between oncocytoma and epithelial malignant lesions with oncocytic features in the kidney; therefore, patients must undergo resection or, in certain circumstances, biopsy to definitively establish diagnosis. Immunohistochemical staining for CD10 and CD3, evaluation of the staining pattern and intensity, and relevant morphologic appearance are helpful diagnostic tools in discriminating between renal cell carcinoma with oncocytic features and renal oncocytoma. Electron microscopy confirms different ultrastructural components of each neoplastic cell type and correlates with immunohistochemical findings. Accurate determination of the tumor origin would allow for the use of limited nephron sparing and laparoscopic surgical approaches to treat appropriately.