Diabetic mastopathy: a report of 5 cases and a review of the literature.

BACKGROUND: Diabetic mastopathy is an unusual fibroinflammatory breast lesion that characteristically presents in premenopausal women with long-standing type 1 diabetes mellitus with multiple microvascular complications. The pathogenesis of this condition is believed to involve an autoimmune reaction to the accumulation of abnormal matrix induced by hyperglycemia. Clinicopathologic features include the development of dense keloidlike breast masses that are often recurrent or bilateral or both. Clinical distinction from a malignancy can be difficult. However, the benign nature of this lesion is easily recognized on histologic examination, and it is not associated with an increased incidence of epithelial or stromal neoplasia. HYPOTHESIS: A constellation of histopathologic and clinical features is necessary to make the diagnosis of diabetic mastopathy. Unnecessary surgery can be avoided in the clinical follow-up of patients with multiple, bilateral, and recurrent lesions. DESIGN: Case series. PATIENTS AND METHODS: Between December 1993 and December 1998, 5 premenopausal women with type 1 diabetes mellitus of 18 to 23 years' duration presented with nontender, palpable, firm-to-hard breast masses. To date, progression of the tumorlike proliferations has been bilateral and recurrent in 2 patients, bilateral in a third patient, and recurrent in a fourth. The fifth patient has developed neither bilateral nor recurrent lesions. Imaging studies did not in any patient demonstrate a focal lesion. All lesions were treated by either excisional (4 patients) or core (1 patient) biopsy. The resected specimens were examined histopathologically. RESULTS: Gross examination of the specimens showed firm masses with homogeneous tannish-white cut surfaces. They measured between 3.0 and 6.0 cm in maximum diameter. Microscopic examination showed keloidal fibrosis with ductitis, lobulitis, and vasculitis. The clinical profile in combination with these pathologic features is characteristic of diabetic mastopathy. CONCLUSIONS: Physicians should be aware of the association of long-standing diabetes mellitus with the development of benign fibroinflammatory breast lesions when managing these in premenopausal women. We outline the constellation of findings on clinical examination, medical history, imaging studies, and histopathologic examination that are required to make the diagnosis of diabetic mastopathy. Although these breast masses may be recurrent, they are not premalignant. In the appropriate setting, the diagnosis can be made by core biopsy, avoiding unnecessary surgeries in patients with multiple, bilateral, or recurrent lesions.

Intracranial Approach to Suprasellar Rathke's Cleft Cyst.

The occurrence of a symptomatic Rathke's cleft cyst without extension into the sella turcica is rare. The purpose of this report is to present such a case, with its clinical manifestation, diagnostic imaging characteristics, operative approach, pathology and review of the literature.

Cholestatic jaundice due to ackee fruit poisoning.

A 27-yr-old Jamaican male presented with a 2-month history of jaundice, pruritus, intermittent diarrhea, and right upper quadrant abdominal pain. Over the next month, his abdominal pain and diarrhea improved, but his jaundice and pruritus worsened. He was afebrile and profoundly jaundice, with a benign abdominal examination. Medical workup included a normal abdominal ultrasound, iron studies, ceruloplasm, and serum electrophoresis. Negative viral (Epstein-Barr virus, cytomegalovirus, mononucleosis, hepatitis A, B, C) studies, ANA, AMA, ASMA, RPR were noted. He denied any alcohol, drug, or toxin exposure. Liver tests revealed total bilirubin of 25.6 mg/dl, direct bilirubin of 13.9 mg/dl, alkaline phosphatase 278 IU/L, AST 45 IU/L, and ALT 71 IU/L. Liver biopsy demonstrated centrilobular zonal necrosis and cholestasis most consistent with a toxic reaction. The patient was again interviewed regarding potential toxins, and he admitted to the ingestion of ackee fruit, a native Jamaican fruit that is illegal in the United States. Shortly after he had ceased intake of the fruit, his symptoms resolved and his liver function tests returned to normal. We present a case of chronic ackee fruit ingestion that led to cholestatic jaundice, vomiting, and abdominal pain.

Cholestatic jaundice due to ackee fruit poisoning

A 27 year old Jamaican male presented with a 2 month history of jaundice, pruritus, intermittent diarrhea, and right upper quadrant abdominal pain. Over the next month, his abdominal pain and diarrhea improved, but his jaundice and pruritus worsened. He was afebrile and profound jaundice, with a benign abdominal examination. Medical workup included a normal abdominal ultrasound, iron studies, ceruloplasm, and serum electrophoresis. Negative viral (Epstein Barr virus, cytomegalovirus, mononucleosis, hepatitis A, B, C) studies, ANA, AMA, ASMA, RPR, were noted. He denied any alcohol, drug, or toxin exposure. Liver tests revealed total bilirubin of 25.6 mg/dl, direct bilirubin of 13.9 mg/dl, alkaline phosphate 278 IU/L, AST 45 IU/L, and ALT 71 IU/L. Liver biopsy demonstrated centrilobular zonal necrosis and cholestasis most consistent with a toxic reaction. The patient was again interviewed regarding potential toxins, and he admitted to the ingestion of ackee fruit, a native Jamaican fruit that is illegal in the United States. Shortly after he had ceased intake of the fruit, his symptoms resolved and his liver function tests returned to normal. We present a case of chronic ackee fruit ingestion that led to cholestatic jaundice, vomiting, and abdominal pain (AU)

Flow cytometric and genetic study of familial gonadal tumors.

Three cases of familial gonadal tumors are reported. Genetic studies were conducted in 2 cases: a brother and sister with embryonal carcinoma and a benign cystic teratoma, respectively, and a father and son with embryonal carcinoma. DNA flow cytometry of paraffin-embedded tumors and constitutional karyotyping were performed. Further genetic studies are emphasized.

Adrenal cortical carcinoma: flow cytometric study of 22 cases, an ECOG study.

Flow cytometric studies of archival material from 22 adrenal carcinomas demonstrated aneuploidy in 21 of 22 cases. Heterogeneity of nuclear DNA was found in 14 of the 22 cases. Eight of these showed distinct aneuploid and diploid populations, and 6 showed multiple aneuploid cell lines. The heterogeneity was detected because numerous paraffin-embedded samples of each tumor could be examined. No correlation was found between either aneuploidy or heterogeneous DNA content and patient survival, response to therapy, or hormone secretion.

Wilms' tumor: a search for the critical lesion.

A Wilms' tumor from a 12-month-old boy showed epithelial and mainly rhabdomyoblastic differentiation. In addition, the kidney contained foci of nephroblastomatosis, a lesion predisposing to the development of nephric tumors. Flow cytometry indicated that the tumor DNA content was in the diploid range with an increased S-phase. Chromosome studies of the cultured tumor cells showed a dominant pattern of 49,XY, +8,9qh+, +12, +12,18q+, without obvious deletion of 11p. A few cells showed additional losses, deletions, or structural rearrangements superimposed on the basic pattern, but no normal metaphases were observed. The DNA from the tumor was probed for several loci on 11p because variations of 11p (deletion or translocation) have been reported in roughly one third of Wilms' tumors, and the critical gene in Wilms' has been localized to 11p13. In this case, 11p genes maintained heterozygosity or showed no detectable alteration in gene dosage when compared with peripheral-blood DNA. Therefore, despite histologic indication of an underlying constitutional defect, no genomic lesion of 11p was identified.

The role of liver biopsies in psoriatic patients receiving long-term methotrexate treatment. Improvement in liver abnormalities after cessation of treatment.

Liver biopsy specimens from 168 patients who underwent a total of 364 biopsies were examined. Of 83 patients receiving biopsies before methotrexate treatment, 14 had one or more risk factors predictive of liver abnormality but they had normal pretreatment biopsy specimens. Among 17 patients with abnormal biopsy specimens before methotrexate treatment, only 1 had an identifiable risk factor and 5 had abnormal results of liver function tests. The probability of a normal biopsy specimen after methotrexate treatment dropped below 50% at a cumulative methotrexate dose of 3115 mg for the 31 patients with biopsy specimens from before and after methotrexate treatment and 5776 mg for those who had biopsies only after methotrexate treatment; this difference was statistically significant and is thought to be related to the fact that the patients who had biopsies before and after methotrexate treatment had received most of their medication by the parenteral rather than the oral route. A significant association existed between biopsy grade after methotrexate treatment and obesity. Other risk factors were not correlated with biopsy grade. Blood chemistry tests were not predictive of histopathologic findings. Eight of 11 patients with fibrosis or cirrhosis showed meaningful improvement in liver histologic findings after methotrexate treatment had been withdrawn for 6 months or more; none had progression of abnormalities.

Flow cytometry of fetal adrenal glands with adrenocortical cytomegaly.

Adrenal glands from four autopsied fetuses of 18 to 36 weeks gestation showed varying degrees of cortical cytomegaly. Formalin-fixed, paraffin-embedded sections from these four pairs of glands were studied by flow cytometry to analyze their DNA content and cell cycle parameters. Flow cytometry of Case 1, which had diffuse bilateral cytomegaly, demonstrated a major diploid peak, an increased percentage of tetraploid cells, and a decrease in S phase compared to an age-matched control with no evidence of cytomegaly (Case 2). Cases 3, 4, and 5 showed focal and/or unilateral adrenocortical cytomegaly and were diploid by flow cytometry with no differences in synthetic or tetraploid fractions compared to the control tissues. The focal distribution of the lesions or the limits of resolution of the instrumentation could account for some of these results. However, the findings in Case 1 suggest that the cytomegalic cells are tetraploid in DNA content and may have decreased DNA synthetic activity. A current hypothesis that these cells have undergone a period of sustained hyperactivity followed by exhaustion in reaction to an unknown stimulus is supported by our observations.

Cytogenetic, flow cytometric, and ultrastructural studies of twenty-nine nonfamilial human renal carcinomas.

Multifactorial analysis, including cytogenetic studies, flow cytometry, and light and electron microscopic evaluation, was performed on 29 primary renal cell carcinomas and short-term cultures derived from them. Eleven of the 21 cases that yielded cytogenetic results demonstrated clonal chromosomal aberrations which included trisomy 7 in 8 cases, loss of the Y chromosome in 7, trisomy 12 in 2, and 16q- in 1. Flow cytometry showed that there was preferential growth of near-diploid populations and loss of aneuploid clones in culture with standard media. The ultrastructural features of both the primary and cultured tumors were remarkably similar. They included cytoplasmic vacuolization, reticulated dense nucleoli, and cell surface microvilli. Thus, morphological evidence supported the epithelial and, specifically, the renal tubular origin of the cultured cells. The development of chromosomal abnormalities seemed linked to advanced tumor stage, but the number of such cases was too small to analyze for statistical significance. No other correlations could be made between karyotypic change, DNA analysis, tumor histology, grade, and stage at this point in the patient follow-up.

Cytogenetic diversity in primary human tumors.

Cytogenetic patterns from primary short-term culture of breast cancer, renal carcinoma, and tumors of the central nervous system are presented to illustrate the range of karyotypic diversity of human solid tumors as well as their biologic differences in culture systems that support their growth. These studies have illustrated several major issues. 1) Results vary with the tissue of origin: primary cultures from breast are almost uniformly diploid, while renal tumors are near-diploid, mosaic, and show clonal aberrations; and CNS tumors are heterogeneous: some diploid, some near-diploid and some highly aneuploid. 2) Results after short-term culture are selective, representing subpopulations from the heterogeneous cells that are detected on direct analysis of fresh tumors by cytogenetics or flow cytometry (FCM). It is not yet clear whether prognosis depends on the dominant population of the primary tumor or alternatively should be influenced by detection of small aneuploid subpopulations. 3) Evidence from all three tumor types supports the interpretation that cytogenetically normal diploid cells constitute part of some tumor populations, and may be better adapted to routine growth in culture than aneuploid subpopulations from the same primary tumors. These cells may also compose a major portion of the viable population of tumors in vivo and, therefore, could represent a useful model for studies of tumorigenesis and therapeutic regimens.

Long-term effects of etretinate on the liver in psoriasis.

Etretinate is an aromatic retinoid and derivative of vitamin A soon to be approved for general use in the U.S. as therapy for severe psoriasis. We report on liver morphology and function in 18 subjects who received the drug for at least 5 years as part of a clinical trial. The majority (14) suffered no or mild and reversible structural liver changes; mild transient elevations in serum triglyceride and liver enzymes were noted occasionally. Of the remaining four patients, mild periportal fibrosis was documented in two, another had changes similar to chronic active hepatitis, and a fourth had cirrhosis that was unrelated to alcohol use. Liver function data, cumulative drug dose, and treatment duration were generally not reflective of these changes. The results of this study suggest a need for periodic liver biopsy to monitor patients on long-term etretinate therapy.