Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium.

OBJECTIVES: To determine whether cyclooxygenase-2 (COX-2) expression is seen in endometrial cancer, endometrial hyperplasia, and normal endometria and whether it correlates with expression of estrogen and progesterone receptors. METHODS: The study was a retrospective, IRB-approved analysis of biopsy samples from 14 patients with endometrial adenocarcinoma, 19 with endometrial hyperplasias, and 10 with normal endometrium. Excluded were samples from women with a history of pelvic radiation, NSAID use, or treatment with hormones during previous year. Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissues. Expression of COX-2, estrogen and progesterone receptors were scored according to the proportion of positive-staining cells: 1(+), <10%; 2(+), 10-50%; and 3(+), >50%. A score > or =2(+) was considered positive. Fisher's exact test and analysis of variance were used to compare proportions and continuous variables, respectively. RESULTS: Overexpression of COX-2 was seen in 4 (29%) of the endometrial cancers, 6 (32%) of the endometrial hyperplasia, and 4 (20%) of the normal endometria. These differences were not statistically significant (P = 0.90). No COX-2 expression was found in stromal tissue. Of 14 endometrial cancers, 7 (50%) expressed any COX-2, with 4 (29%) having an expression score of > or =2(+). Of 19 endometrial hyperplasias, 11 (58%) expressed any COX-2; with 6 (32%) having a score of > or =2(+). All 10 normal endometria showed only 1(+) expression. No significant differences were detected in COX-2 expression by grade or stage of cancer. Although 100% and 95% of both hyperplasia and normal endometrium samples expressed in estrogen and progesterone receptors, respectively, only 71% and 79% of endometrial cancers expressed estrogen and progesterone receptors (P = 0.01). A nonparametric trend was performed to detect a relationship, between COX-2 and estrogen receptor or progesterone receptor expression; no significant trend was found. CONCLUSIONS: In this study, the immunohistochemical analysis showed a trend toward increased COX-2 expression in endometrial cancer and hyperplasia compared to normal endometria. A larger sample size is needed to confirm these results. The increased COX-2 expression in hyperplasia may signify an early step in carcinogenesis. These findings may represent an important treatment opportunity for synergism in the hormonal therapy of endometrial cancer.

Pilomatrixoma: a diagnostic pitfall in fine-needle aspiration biopsies. A review from a small county hospital.

A 10-year-old Hispanic girl presented with a 3-cm mass over her right parotid region. A fine-needle aspiration (FNA) was performed and the preliminary and final diagnoses were "suspicious for carcinoma, possible mucoepidermoid carcinoma." A subsequent computed tomography demonstrated an extra-parotid lesion attached to the skin. The FNA smears were reviewed and the diagnosis of a pilomatrixoma (PMT) was reached. The lesion was excised and the diagnosis of benign PMT confirmed. Pilomatrixomas are uncommon skin adnexal tumors most commonly found in the head and neck area of young adults and children. In 10 years there were 16 PMTs among 60,280 surgical pathology specimens in the pathology files of our 300-bed general county hospital. Pilomatrixoma is recognized as a diagnostic pitfall not only clinically but also on FNA cytology. On the physical examination, the bluish skin discoloration over the lesion so typical of PMT was overlooked. On FNA, the basaloid cells of PMT were mistaken for intermediate cells of mucoepidermoid carcinoma. The presence of anucleated squames was not properly recognized. These are usually absent in mucoepidermoid carcinoma and represent a hallmark of PMT. This case illustrates well the risk of misdiagnosing a pre-auricular PMT as a malignant tumor of the parotid gland.

Pediatric medullary carcinoma of the thyroid with point mutation of RET proto-oncogene associated with multiple endocrine neoplasia and initially diagnosed by fine-needle aspiration biopsy.

A 7-year-old girl presented with a thyroid mass, elevated serum levels of calcitonin and carcinoembryonic antigen, as well as multiple mucosal nodules in the upper lip and tongue. Cytologic material obtained by fine-needle aspiration biopsy from the thyroid mass was diagnosed as medullary carcinoma and confirmed by immunohistochemical studies in the cell-block sections. Subsequent histopathologic examination showed involvement of both thyroid lobes by medullary carcinoma, and electron microscopic studies further confirmed the diagnosis. Molecular studies showed a point mutation in amino acid 918 in exon 16 of the RET proto-oncogene. Biopsies from the upper lip and tongue showed mucosal neuromas. Fine-needle aspiration biopsy is frequently used in the initial evaluation of thyroid nodules. This case illustrates the value of fine-needle aspiration biopsy as a safe and accurate diagnostic modality in the workup of pediatric thyroid nodules. Fine-needle aspiration biopsy should always be considered for the investigation of thyroid nodules in pediatric patients.

Blastomycosis: The great pretender can also be an opportunist. Initial clinical diagnosis and underlying diseases in 123 patients.

Clinically, blastomycosis can be difficult to recognize even in the endemic areas where clinicians are aware of this problem. In only 18% of 123 patients from the University of Mississippi Medical Center (Jackson, MS) blastomycosis was correctly suspected at the initial patient evaluation. Pneumonia sensu latu (40%), malignant tumors (16%), and tuberculosis (14%) were the most common misdiagnoses. The false first impression frequently resulted in unnecessary surgeries or treatment delays, with patients receiving inefficient antibiotic therapy for months. The presence of cutaneous involvement by the disease makes its' recognition easier for the clinician, raising the percentage of correct initial diagnosis to 64%. To evaluate the association with immunodepression, the presence of other diseases was also searched among the 123 patients. An immunodepressive condition preceded the fungal disease in 25% of patients. Another associated disease commonly found in blastomycotic patients was diabetes mellitus (22%). Blastomycosis is correctly suspected at the first clinical evaluation in only a small percentage of patients; pneumonia, cancer, and tuberculosis are the most common clinical considerations. Cutaneous involvement leads the clinician to the correct diagnosis in the majority of cases. One fourth of the patients with blastomycosis had underlying immunodepressive conditions, and underlying diabetes mellitus is present in 22% of patients.

Pseudoneoplastic proliferation of histiocytes with paclitaxel-induced ultrastructural changes in a mastectomy specimen.

A 49-year-old Hispanic woman with a T4N1M0 infiltrating duct carcinoma of the left breast underwent four courses of FAC (doxorubicin 86 mg, 5-fluorouracil 860 mg, cyclophosphamide 86 mg, and dexamethasone 10 mg) adjuvant chemotherapy plus four courses of paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ) and subsequent mastectomy. The tumor shrunk from 6.5 cm to 2.5 cm after the treatment. The residual tumor in the surgical specimen measured 1.5 cm with eight positive out of 24 axillary lymph nodes. The tumor showed typical chemotherapy changes and a massive proliferation of histiocytes that mimicked a neoplasm. A nodular proliferation of the same cells in one axillary node raised the impression of a second malignant tumor in the breast spreading to the node. The histiocytic cells contained lamellar and coarse periodic acid-Schiff-positive material distending their cytoplasm and they were strongly positive for CD68 and negative for CD1a, pan keratin, and S-100. These findings ruled out histiocytoid carcinoma, granular cell tumor, and Erdheim-Chester disease. The proliferating histiocytes had ultrastructural findings of paclitaxel-induced cytotoxicity with disorganized stacks of intermediate filaments positive for vimentin by immunostains and fewer masses of tubulin. The treated breast carcinoma cells were tubulin-positive but the proliferating histiocytes were tubulin-negative.

Blastomycosis and pregnancy.

Blastomycosis is an exceedingly uncommon complication of pregnancy, rarely encountered by the practicing obstetrician. However, recognizing its presence during pregnancy and expeditiously initiating appropriate therapy is of critical importance to the mother and fetus. Mississippi has the highest prevalence of blastomycosis in North America. Nevertheless, there have been only three pregnancies complicated by this fungal disease at the University of Mississippi Medical Center (Jackson, MS) during two decades. During the same time frame there were another 120 blastomycotic patients treated at the University of Mississippi Medical Center. As a condition of partial immunodepression, a nonobligatory opportunistic fungal disease like blastomycosis can complicate pregnancy. From data on our three patients and 16 other published cases, it seems that fetal risk exceeds maternal risk. There were a total of 20 babies born from mothers with blastomycosis. Only two babies (10%) had transplacental infection and both succumbed to blastomycosis. None of the 18 affected mothers for whom data was available died of the disease. Furthermore, there was never progression in the mothers, with 14 complete cures and considerable postpartum regressions of lesions in the other four women. Even the three women who received no treatment had either noticeable improvement or total regression of the disease after delivery. One of the two stillborns with blastomycosis was born to an untreated mother.

Hyperinfection syndrome in strongyloidiasis: report of two cases.

Hyperinfection in strongyloidiasis has been associated with corticosteroid treatment. Other immunodepressive conditions also seem to facilitate the state of hyperinfection. The etiologic diagnosis of this parasitosis can be difficult to reach and a positive urine microscopy is unusual. We report two patients under corticosteroid therapy with disseminated strongyloidiasis; both had eosinophilia. The first patient, followed for 8 years for autoimmune hemolytic anemia, recently developed abdominal symptoms. A colonoscopy was performed 1 month before admission and the biopsy was thought to show nonspecific changes. At admission, few larvae of Strongyloides stercoralis were disclosed by urine microscopy, and a review of the colonic biopsy uncovered a few larvae of Strongyloides. The patient received anti-helmintic therapy with a dramatic improvement. The second patient, under treatment for lupus erythematosus for 3 years, was admitted with pulmonary symptoms and during admission developed massive gastrointestinal bleeding. Disseminated strongyloidiasis was discovered only at autopsy. The low suspicion index for strongyloidiasis resulted in delaying the etiologic diagnosis in one patient and in failing to diagnose the disease in the other. The morphologic features of the parasite in the two cases are presented with emphasis on the difficulties of recognizing the larvae in the intestinal biopsy.

Prevention of alpha-naphthylthiourea-induced pulmonary edema with fructose-1,6-diphosphate.

Neutrophil-derived oxygen free radicals have been implicated in the pathogenesis of noncardiogenic pulmonary edema. Fructose-1,6-diphosphate (FDP) has been shown to inhibit oxygen free radicals production by activated neutrophils. Thus, we investigated whether FDP would attenuate formation of pulmonary edema in anesthetized dogs injected with alpha-naphthylthiourea (ANTU). Hemodynamic studies involved measurements of left ventricular systolic and end-diasystolic pressures (LVSP and LVEDP), pulmonary artery pressure (PaP), heart rate (HR), and cardiac output (CO). Mean wet weight to dry weight ratios of lung tissue samples were calculated. Following baseline measurements, dogs were injected intravenously (IV) with ANTU 5 mg / kg (n = 16) and 10 mg / kg (n = 8) and half of the dogs were randomly selected to receive 75 mg / kg FDP (10%) and subsequent infusion of 7 mg / kg / min. The rest were given 0.9% NaCl in the same manner. Four hours after ANTU administration, the animals were euthanatized. Except for decline in the CO (nonsignificant), no significant changes in systemic hemodynamics within and between the groups were noted. In the FDP group, PaP and pulmonary arteriolar resistance (PaR) remained unchanged. In the saline group, PaP increased from 12.5 +/- 2.44 to 21.8 +/- 3.14 mm Hg (P < .001) and PaR from 166 +/- 29 to 468 +/- 74 dynes. cm / sec(5) (P < .005). During the study LVDEP, PaO(2), PaCO(2), and hematocrit did not change significantly within and between the groups. The lungs mean wet weight to dry weight ratios for the sham-operated dogs were 4.20 +/- 0.41, for the FDP group 4.32 +/- 0.59 and 6.22 +/- 1.37 for the saline group (P < .0005). These data indicate that FDP protected the lung from ANTU-induced injury.

Punçäo biópsia aspirativa de nódulos tiroidianos com agulha fina e grossa: resultados de 149 casos operados no Hospital do Servidor Público Estadual de Säo Paulo e Hospital Santa Catarina, Säo Paulo / Aspiration of thyroid nodules with nudles of different sizes: results in 149 cases operated at the Hospital do Servidor Público Estadual de Säo Paulo and Hospital Santa Catarina, Säo Paulo

Os autores analisam os resultados obtidos na punçäo aspirativa com agulha em 149 casos de bócio (146 nodulares) operados e confronta-os com o diagnóstico anátomo-patológico definitivo de peça operatória. O estudo foi realizado em dois grupos de doentes com diferentes metodologias. O grupo A consistiu de 57 casos, operados no Hospital Sta. Catarina, Säo Paulo; a punçäo foi feita com agulha grossa (calibre 1,4 a 1,8mm) na peça cirúrgica já retirada. O confronto entre o exame citológico do aspirado e o histopatológico definitivo revelou cerca de 13% de falsos positivos e 4,9% de falsos negativos. O grupo B consistiu de 89 casos (de 92 aspirados em 3,0 material foi insuficiente), operados no Hospital do Servidor Público Estadual de Säo Paulo; nestes a punçäo aspirativa transcutânea foi feita com agulha fina (calibre 0,45 a 0,7mm) alguns dias, antes da operaçäo. Os resultados foram: cerca de 20% de falsos positivos; 10% de falsos negativos e cerca de 83% de falsos suspeitos. Diante desses resultados, semelhantes aos da literatura, os autores ponderam que essa prova, ainda recente, em nosso meio, deve ser aprimorada para entrar na rotina como elemento diagnóstico