Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma.

Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)-androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.

Evidence that the effectiveness of antioxidants as inhibitors of 7,12-dimethylbenz(a) anthracene-induced mammary tumors is a function of dietary fat composition.

A study of tumor incidence and tumor growth rates in 7,12-dimethylbenz(a)anthracene-treated female Sprague-Dawley rats fed different types and amounts of dietary fat indicates that the difference in tumor incidence may be a reflection of marked differences in the growth of neoplastic clones to a palpable size within the time frame of the study. In addition, the observation is made that some antioxidants which inhibit tumor development in animals fed commercial rations are not effective when given in purified diets.

Continuing disease process of calcific aortic stenosis. Role of microthrombi and turbulent flow.

Microthrombi with evidence of organization were observed in 10 of 19 calcified and stenotic aortic valves (53 percent). The organization that results from such thrombi may contribute to the deformity of the valve. Repetitive deposits of microthrombi, followed by organization and calcification, would explain the continuous process of stenosis in previously deformed aortic valves. The formation of such thrombi may be initiated by turbulent flow and other fluid dynamic factors.

Myofibroblastoma of the breast revisited: an etiologic association with androgens?

Myofibroblastoma of the breast is an uncommon benign stromal tumor encountered predominantly among elderly men. Histologically, myofibroblastoma is a well-circumscribed tumor comprised of bipolar spindle cells arranged in short fascicles traversed by collagen bundles. Based on previous histological, immunohistochemical, and ultrastructural observations, this tumor is thought to be derived from myofibroblasts. The pathogenesis of myofibroblastoma is unknown. Given the demographics of this lesion, the established trophic effect of steroid hormones, and the potential diagnostic utility of hormone receptor analysis in differentiating spindle cell tumors, we immunohistochemically tested for estrogen and androgen receptors in a host of spindle cell lesions including myofibroblastoma of the breast. Five cases reported herein of histological confirmed myofibroblastoma obtained from male and female breasts each showed strong nuclear antibody staining for the androgen receptor, not seen in four cases of leiomyosarcoma, three cases of fibromatosis, three cases of dermatofibrosarcoma protuberans, and two cases of monophasic synovial sarcoma. We postulate that the androgen receptor or its ligands may be pathologically related to the development of myofibroblastoma of the breast and diagnostically useful in differentiating it from other spindle cell lesions.

Prolonged survival after cardiac rupture following myocardial infarction.

This report describes a patient who suffered rupture of the anterior wall of the left ventricle following an acute myocardial infarction and survived for 12 days before dying from cardiac tamponade. Rupture of the heart presented as an asymptomatic pericardial effusion.

Adult T-cell leukemia: clinical and immunologic characterization of a nonendemic case.

A 56-year-old black man with nonendemic adult T-cell leukemia is reported, who presented with severe hypercalcemia and leukemic leptomeningeal infiltration but had no evidence of bone marrow involvement. His malignant cells were characterized by light and transmission electron microscopy, cytogenetics, and flow cytometry. The cells demonstrated the deeply indented or convoluted nuclei characteristic of endemic human T-cell lymphoma virus-associated cases. Surface phenotyping indicated the cells' origin to be from the mature, helper/inducer subset of T-lymphocytes. However, there was no clinical or laboratory evidence that the malignant cells retained immunoregulatory function. The clinical and immunologic features of this and other nonendemic cases are compared with those of patients from the endemic regions of Japan, the Caribbean islands, and the southeastern United States.

Acute leukemia after successful chemotherapy for oat cell carcinoma.

A report of acute myelomonocytic leukemia following successful therapy for oat cell carcinoma is presented. The patient had been treated with extensive cytotoxic and radiation therapy, and was without clinical evidence of disease at one year follow-up. Eighteen months later, a peripheral smear revealed numerous blasts with monocytoid characteristics. This unusual presentation is discussed and compared with several other cases appearing in the recent literature.

Pigmented lesions in actinically damaged skin. Histopathologic comparison of biopsy and excisional specimens.

BACKGROUND AND DESIGN: A consecutive sample of 46 cases was collected for comparative histologic evaluation. Results of incisional biopsies of cutaneous pigmented lesions interpreted as lentigo maligna, melanoma in situ, or invasive melanoma, and those suggestive, but not diagnostic, of melanoma were collected. Those lesions that were on actinically damaged skin and in which biopsy was followed by complete excision within 6 months were included. Incisional biopsies that removed greater than 50% of the surface area of the lesion were excluded. RESULTS: Of the excisional specimens, 40% demonstrated histopathologic features more pronounced than those in the biopsy specimens. Areas of invasive melanoma not detected in the biopsy specimens were observed in 20% of the excisional specimens. Accurate diagnosis based on small biopsy specimens was not always possible because of the absence of a classic lentigo maligna histologic pattern in many cases. The most frequent deviation from the pattern was the presence of lentiginous epidermal hyperplasia within these lesions. CONCLUSIONS: These results suggest that limited sampling may be inadequate for an accurate diagnosis of pigmented melanocytic lesions on actinically damaged skin. Areas chosen for biopsy may not contain the most advanced areas histologically and may fail to detect foci of invasive melanoma elsewhere within the lesion.

Rochalimaea henselae infection in acquired immunodeficiency syndrome causing inflammatory disease without angiomatosis or peliosis. Demonstration by immunocytochemistry and corroboration by DNA amplification.

Rochalimaea henselae causes bacillary angiomatosis, bacillary peliosis, and persistent bacteremia. Difficult to cultivate, it is detectable in infected tissues by immunocytochemistry. This technique demonstrated R henselae in autopsy specimens obtained from three deceased patients who had acquired immunodeficiency syndrome, with pathologic tissue changes lacking neoangiogenic features. From the first patient, the cause of nodular collections of lymphocytes and nonepithelioid histiocytes in the liver, spleen, lymph nodes, bone marrow, and heart eluded detection until immunocytochemical identification of R henselae. In the second case, unexpected gross and microscopic necroinflammatory nodules in the liver and spleen contained Warthin-Starry-staining bacilli identified as R henselae immunocytochemically. The third patient was found to have pathologic changes in his liver and spleen comparable with those of the second case, as well as several other disseminated infections. In two cases, identification of R henselae was corroborated through sequencing polymerase chain reaction-amplified bacterial DNA recovered from tissue; in one case, DNA could not be amplified, possibly because of postmortem degradation. Application of the immunocytochemical technique thus has expanded the recognized spectrum of histopathologic findings associated with R henselae infection in acquired immunodeficiency syndrome, as well as proving to be potentially more sensitive than DNA amplification for this purpose when applied to autopsy tissues.

Delayed reaction to "lead" pencil simulating melanoma.

A 74-year-old man had sustained a penetrating lead pencil injury to his right lower leg at the age of fifteen. A dark gray macule occurred that remained unchanged for fifty-eight years. An enlarging black nodule appeared in this area, simulating a melanoma, when the patient was seventy-three years old. Histologic examination revealed exogenous pigment and a foreign body reaction.

9p21 deletions in primary melanoma.

Formalin-fixed, paraffin-embedded primary melanoma biopsies were evaluated for evidence of genomic loss on the short arm of chromosome 9 using microsatellite PCR assays for the D9S157, D9S161 and D9S171 loci. Paired normal and tumor DNA was extracted from the same block for comparison of microsatellite marker patterns. Some detectable abnormality was seen in at least one of these loci in 15 of 44 evaluable specimens (34%). Homozygous deletions were detectable at these loci in 8 of 44 informative specimens (18%) and hemizygous deletions were seen in 11 of 44 informative specimens (25%). Deletions at 9p were more likely to be found as primary tumor thickness increased (p < 0.05). This evidence supports the concept that 9p21 deletions are involved in primary sporadic melanomas, and that 9p deletions are not solely an in vitro phenomenon.

Spontaneous haematomyelia: a necropsy study.

Spontaneous haematomyelia (intramedullary spinal haematoma), is an uncommon event. Predisposing conditions have been reported including syringomyelia, pregnancy and delivery, angioma, spinal artery aneurysm, and haemophilia, but only rarely has a pathological evaluation been performed. Two such cases studied at necropsy are reported. In one case, the haematoma was restricted to the cervical spinal cord, while in the second case it extended from the medulla into the lowest thoracic cord segments. In both cases the haematomyelia was fatal. In the first case the clinical course was subacute, but in the other the course was more acute. Careful neuropathological examination showed no apparent cause for the haemorrhages.

Subcutaneous fat necrosis in pancreatitis.

A case of subcutaneous fat necrosis as the initial manifestation of an attack of acute pancreatitis is presented. The accompanying features of respiratory distress syndrome, leukemoid reaction, shock, pleural effusions, and arthritis due to necrosis of periarticular fat are described. Autopsy findings are pancreatic pseudocyst, serofibrinous peritonitis, pleuritis, and pericarditis and fat necrosis not only in the subcutaneous fat but also in the pericardial, pleural, mediastinal, mesenteric, retroperitoneal, and pericalyceal fat.

Histologic and electrophysiologic changes following subepineurial hematoma induction in rat sciatic nerve.

The sciatic nerves of 34 rats were used to study the effects of intraneural, extrafascicular hematoma, exclusive of any other trauma. Electrodiagnostic, histologic, and electron microscopic techniques were used. The amount of nerve fiber damage was assessed using computerized planimetry. The effects of hematoma evacuation were also investigated. Changes consistent with partial denervation, such as prolongation of insertion activity and distal latency, and the presence of positive waves and fibrillations, were present in the blood-injected but not in the control groups. Degenerative nerve fiber changes localized to the area of hematoma were present in the blood-injected group and were significantly higher than those in the control group. Although there was a difference in the amount of nerve damage between the blood-injected and the hematoma-evacuated group (less damage), this difference was not statistically significant. These findings suggest that intraneural extrafascicular hematoma produces electrophysiologic and histologic evidence of axonal degeneration affecting nerve fibers in the vicinity of the hematoma. Early evacuation of the intraneural hematoma appears to slightly reduce the deleterious effects of the lesion.

Vaterian cancer in siblings.

The simultaneous occurrence of Vaterian carcinoma in two siblings suggests a genetic influence in their pathogenesis. Their classic clinical presentation of obstructive jaundice and weight loss required pancreaticoduodenectomy for this neoplasm. Pedigree analysis revealed a third sibling who died from an unresectable periampullary malignancy. Neither of the probands exhibited, as late as the seventh decade, evidence compatible with a diagnosis of familial polyposis coli or Gardner's syndrome. Flow cytometry studies revealed an aneuploid distribution in one tumor and tetraploid in the other. The rarity of this neoplasm, in the absence of contributing epidemiologic factors, suggests that this is a pleotrophic manifestation of a cancer-prone genotype.

Ultrastructural studies of vascular lesions in experimental amyloidosis of mice.

Definite lesions of arteriolar capillaries have been demonstrated in early amyloid lesions of mice. Pathologic changes include multiple endothelial gaps, the loss of an identifiable basal lamina, variable degrees of endothelial alteration, and the presence of the developing amyloid lesions surrounding the affected vessels. Despite these changes, the vessels remain functional part of the local microcirculation as demonstrated by intravascular injection of electron dense markers. These structural changes of arteriolar capillaries explain the presence of circulating plasma as a constant and major component of the early amyloid lesions in these animals and on this basis may determine the time of onset and site of formation of the lesions. The vascular injury appears to be caused by immunologic reactions to injected foreign antigens which gain a close relation to the structures of these vessels.

Effects of CO2 laser beam on cortical bone.

Sixteen bone blocks from two freshly amputated legs were used to study the effect of CO2 laser on cortical bone. They were divided into two groups. In Group I, the blocks were treated with CO2 laser using 1 mm spot (focused mode). In Group II, they were treated with CO2 laser using 3 mm spot (defocused mode). Two other variables were investigated: the power and time of exposure. Three histologic zones were observed: a superficial zone with black particle deposits (carbonization), an intermediate zone with fibrillations and enlarged empty lacunae, and a deep zone with normal appearing bone. The bony changes in the first two zones combined were superficial in all specimens and did not exceed 200 microns. Increased energy, a focused beam, and time of exposure were all associated with increased matrix changes. CO2 laser can be applied to cortical bone in vitro with minimal residual thermal damage.

Small-diameter invasive melanomas: clinical and pathologic characteristics.

BACKGROUND: Most melanomas when first diagnosed clinically are larger than common benign melanocytic nevi ( > 6 mm). Smaller melanomas, however, may occasionally occur. Yet, very little is known about them. OBJECTIVE: To determine the incidence and delineate the clinical and histologic characteristics of small-diameter invasive melanomas. METHODS: Slides of all melanomas diagnosed between 1984-1993 were reviewed and measured. All invasive lesions less than 6 mm were further scrutinized clinically and morphologically. RESULTS: Among 357 invasive melanomas, 16 (4.4%) were less than 6 mm. Most lesions lacked some of the histologic features usually seen in large melanomas. One half of them were over 0.75 mm deep. Patients with small melanomas were on average 15 years younger than those with large lesions. In females, sites on the upper extremities predominate. In females, small melanomas had clinical signs of melanoma, while in males they resembled nevi. CONCLUSION: Melanomas smaller than 6 mm are not rare. Clinicians and pathologists must learn their features in order to diagnose them properly.