Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.

Ductal carcinoma in-situ arising in mammary-like glands of the vulva.

Recently a variant of cutaneous glands has been recognized in the anogenital region that combines the morphologic and immunohistochemical features of eccrine, apocrine, and mammary glands, so-called 'mammary-like glands of the vulva'. Carcinoma arising in mammary-like tissue of the vulva is a rare occurrence. So far, there have been 11 cases of primary, mammary-type invasive carcinoma and one case of in-situ carcinoma reported in the vulva. We describe an unusual case of ductal carcinoma in-situ without invasion arising in mammary-like glands of the vulva. A 57-year old woman presented with a 1-year history of a 1 cm nodule in the right labium majus. Excision showed ductal carcinoma in-situ with cribriform and papillary morphology in an adenosis-like lesion associated with mammary-like glands. No invasion into the stroma was identified. Immunostains were positive for gross cystic disease fluid protein 15 (GCDFP-15) and estrogen and progesterone receptors. An extensive survey including bilateral mammograms was negative. One year postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the second case of DCIS associated with mammary-like glands of the vulva reported in the English literature.

Pleural amyloidosis mimicking mesothelioma: a clinicopathologic study of two cases.

Two cases of pleural amyloidosis are presented. The patients are two men, 70 and 72 years of age respectively. Neither patient had evidence of systemic amyloidosis. Each presented clinically with symptoms of chest pain and dyspnea. Radiologically, both patients showed diffuse pleural thickening similar to that observed in malignant mesothelioma. In both patients, surgical decortication of the pleura was performed. Histologically, the lesions were characterized by the presence of an amorphous eosinophilic material with focal collections of a lymphoplasmacytic infiltrate. Focal clusters of giant cells were admixed with the lymphoplasmacytic infiltrate. Histochemical stains for Congo red showed strong positive apple-green birefringency. Immunohistochemical studies using kappa and lambda light chains showed polyclonality. The cases discussed herein represent an unusual presentation of amyloid and one that needs to be considered in the differential diagnosis of malignant mesothelioma.

Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases.

AIMS: We describe the clinicopathological characteristics of 15 cases of primary signet ring cell adenocarcinoma of the lung and highlight the importance of recognizing that not all adenocarcinomas with signet ring cell features represent metastatic adenocarcinomas. METHODS AND RESULTS: We evaluated the clinicopathological and immunohistochemical features of 15 cases of signet ring cell adenocarcinoma of the lung. The patients were 12 men and three women, age 30-75 years (mean 52.5 years). No evidence of a primary tumour elsewhere could be found on thorough clinical examination. Nine patients underwent resection and the remainder were biopsied. The tumours ranged from 18 to 80 mm in greatest dimension. Microscopically, two distinct patterns of growth were recognized: acinar and diffuse. The tumours were characterized by the presence of >75% signet ring cells. Periodic acid-Schiff and mucicarmine showed strong intracellular positive staining. Immunohistochemical stains for TTF-1 (6/6) and CEA (9/9) showed strong positive reaction in all cases evaluated. Three out of six cases were also positive for cytokeratin 7. All the tumours (6/6) were negative for cytokeratin 20, ER, PR and GCDFP-15. Follow-up information was obtained in 11 patients; six patients died within 1 year and five patients were alive from 3 to 36 months after initial diagnosis. CONCLUSION: These cases highlight an unusual histological growth pattern of primary lung adenocarcinoma that may be mistaken for a metastasis from an occult primary. The recognition of this pattern of lung tumours is important for proper treatment.

Prognostic significance of percentage of bronchioloalveolar pattern in adenocarcinomas of the lung.

Bronchioloalveolar (BA) carcinoma of the lung is considered to have a better prognosis than that of common adenocarcinomas of the lung. However, a minor component of the BA pattern is common in many lung adenocarcinomas and the criteria for designating an adenocarcinoma as BA are not well defined. We assessed the clinicopathologic features of 238 cases of lung adenocarcinoma with a partial or predominant BA pattern. Tumors were classified as BA if more than 75% of the tumor had a BA growth pattern. In other words, the tumor grew along pre-existing lung structures without invasion or destruction of parenchyma. Tumors with 50% to 75% BA pattern were considered mixed and tumors with less than 50% BA pattern were designated as solid/acinar (S/A). Fixed, paraffin-embedded tissue sections of each neoplasm were also assessed using immunohistochemical methods with a panel of antibodies specific for p53, retinoblastoma protein, p16, cyclin D1, and cyclin E, and the results were correlated with clinical and pathologic parameters. Our results show that the 5-year survival rate of patients with BA and mixed tumors, 63% and 60%, respectively, was significantly better than that of patients with S/A tumors (P =.026). Patients with BA tumors were more frequently women (55.9%) compared with patients with mixed (48.3%) and S/A (43.8%) tumors. Bronchioloalveolar and mixed tumors were similarly associated with tobacco use, 88.2% and 85%, respectively; slightly less than S/A tumors (93.8%). Clinical and pathologic parameters did not correlate with immunohistochemical results. In conclusion, patients with BA or mixed tumors have similar 5-year survival, better than that of patients with S/A tumors, suggesting that adenocarcinomas can be designated as BA when at least 50% of the tumor has a BA pattern.

Androgenic adult granulosa cell tumor in a 13-year-old prepubertal patient: a case report and review of the literature.

We report the clinicopathologic findings of an unusual case of adult granulosa cell tumor with androgenic manifestation in a 13-year-old prepubertal girl. The patient had never had a menstrual period and presented with a 1 year history of hirsutism. Physical examination was only remarkable for an increase in facial and abdominal hair, both with a male pattern of distribution. A pelvic ultrasound demonstrated a 6.0 cm right adnexal cyst. Plasma testosterone and 17-hydroxyprogesterone levels were elevated. The patient initially was treated with monophasic oral contraceptive pills for 3 months and owing to lack of response, she underwent an exploratory laparotomy in which a left ovarian tumor, 7.0 cm in greatest dimension, and a 6.5 cm right paratubal cyst were found. A wedge biopsy of the left ovary and subsequent left oophorectomy with right salpingectomy were performed. No gross evidence of disease outside the ovary was noted. Microscopic examination of the left ovarian tumor revealed the typical features of an adult granulosa cell tumor. No tumor was seen outside the ovary. Six days after surgery, plasma testosterone and 17-hydroxyprogesterone levels were in the normal range. Nine months postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the first case of a prepubertal patient with an adult granulosa cell tumor with androgenic manifestations reported in the English literature.

Prognostic implications of calbindin-D28k expression in lung cancer: analysis of 452 cases.

Calbindin D28k (Ca-D28k) acts as a buffering system to maintain cellular calcium homeostasis and is thought to play a role in inhibiting apoptosis. The goals of this study were to assess CA-D28k expression in lung carcinomas and to correlate these results with patient survival. A total of 452 lung carcinomas were immunostained with a monoclonal antibody specific for Ca-D28K using an avidin-biotin peroxidase technique. The number of cells with nuclear staining was graded semiquantitatively into one of five groups: 0, fewer than 10%, 10 to 25%, more than 25 to 50%, more than 50 to 75%, and more than 75%. Results were correlated with patient survival using Kaplan-Meier survival curves. A total of 335 of 452 (74%) lung carcinomas were positive for Ca-D28k. There was no statistically significant difference in the prevalence of Ca-D28k expression in tumors of different histologic type. Kaplan-Meier survival analysis revealed that for patients with adenocarcinoma, those with Ca-D28k-positive tumors had a better overall survival than patients with Ca-D28k-negative tumors (P = .036). This difference was also significant for patients with Stages I and II adenocarcinomas (P = .033). No statistically significant difference in prognosis was observed for patients with Stages III and IV adenocarcinomas or for patients with other lung carcinoma types of varying stage. Ca-D28k is commonly expressed in lung carcinomas of all histologic types. For patients with localized adenocarcinoma of the lung, Ca-D28k expression correlated with improved survival. No correlation between Ca-D28k expression and patient survival was found for disseminated adenocarcinoma and for other histologic types of lung carcinoma.