Cesar A. Moran

Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases.

We studied 80 cases of primary thymic neuroendocrine carcinomas. Most patients had symptoms; approximately one third were asymptomatic. All cases were treated by surgical excision. The tumors were divided according to histopathologic features into low- (n = 29), intermediate- (n = 36), and high-grade (n = 15) types. The tumors displayed a variegated histologic appearance and unusual cytologic features. Some cases showed transition from low to high grade within the same tumor mass. Mitotic activity ranged from fewer than 3 to more than 10 mitotic figures per 10 high-power fields, and most tumors displayed marked cellular atypia and areas of necrosis. In 73 patients, the tumor was confined to the anterior mediastinum. Positive immunohistochemical reaction was observed using antibodies for CAM 5.2 low-molecular-weight cytokeratins, broad-spectrum keratin, chromogranin, synaptophysin, and Leu-7. The clinical follow-up obtained in 50 patients correlated well with tumor differentiation. Therefore, the behavior of these tumors seems to correlate with histologic grade, which seems directly proportional to degree of differentiation. We propose replacing the term thymic carcinoid with thymic neuroendocrine carcinoma, which better reflects the aggressive biologic behavior of these tumors in the mediastinal location.

Solitary fibrous tumor of the liver: A clinicopathologic and immunohistochemical study of nine cases

Nine cases of primary solitary fibrous tumors of the liver are presented. The patients are 7 women and 2 men between the ages of 32 and 83 years (mean, 57.5 years). Clinically, palpable masses were detected during physical examination in five patients. Two patients presented with symptoms of cholecystitis, one with hematuria, one with periumbilical pain, and one with hypoglycemia. One patient was found to have an abdominal mass during follow-up evaluation for colonic carcinoma, whereas in one patient the tumor was an incidental finding at autopsy. Two patients were asymptomatic, and the tumor masses were detected during a routine physical examination. Grossly, the tumors varied in size from 2 to more than 20 cm in greatest dimension and were described as firm, white-to-gray, well or ill defined. Eight tumors were described as intraparenchymal lesions, two were grossly necrotic, and one tumor was attached by a pedicle to the liver capsule without infiltration into the liver parenchyma. Histologically, most of the tumors had a bland appearance with the classic short storiform (so-called patternless) pattern and absence of cellular atypia, mitoses and/or necrosis. However, in two cases, there was marked cellular atypia and mitotic figures varying from 2 to 4 mitoses per 10 high power field (hpf). Immunohistochemically, all the tumors showed a strong positive reaction against antibodies for CD-34 and vimentin. Follow-up information showed that two patients died within days of postsurgical resection of the tumor, whereas one was alive and well 1 year after initial diagnosis. No follow-up information was available for the other five patients. The cases herein presented highlight the ubiquitous distribution of this neoplasm and the similar clinical and histopathological features to those observed in serosal surfaces. Solitary fibrous tumors of the liver, although rare, need to be considered in the differential diagnosis of mesenchymal lesions of the liver.

Thymic Neuroendocrine Carcinomas With Combined Features Ranging From Well-Differentiated (Carcinoid) to Small Cell Carcinoma A Clinicopathologic and Immunohistochemical Study of 11 Cases

We reviewed 11 cases of primary thymic neuroendocrine carcinomas with combined features ranging from well-differentiated to poorly differentiated neuroendocrine carcinoma. For 3 asymptomatic patients, tumors were discovered during routine examination. Presentation in the other patients was as follows: Cushing syndrome, 2 patients; chest pain, 3 patients; superior vena cava syndrome, 1 patient; and hypercalcemia and hypophosphatemia, 1 patient. No clinical data were available for the 11th patient. All tumors were located in the anterior mediastinum and treated by surgical excision. The lesions were large and well-circumscribed with areas of hemorrhage and necrosis. They were characterized by areas showing a proliferation of monotonous, round tumor cells adopting a prominent organoid pattern admixed with areas showing sheets of atypical cells with hyperchromatic nuclei, frequent mitoses, and extensive areas of hemorrhage and necrosis. Immunohistochemical studies performed in 6 cases showed strong CAM 5.2 low-molecular-weight cytokeratin positivity in all cases, chromogranin and synaptophysin positivity in 4, Leu-7 in 3, and focal positivity for p53 in 2. Follow-up information for 9 cases showed that all patients died of their tumors between 1 and 4 years after diagnosis. The present cases highlight the heterogeneity of neuroendocrine neoplasms and reinforce the notion that these tumors form part of a continuous spectrum of differentiation.

Epithelial-myoepithelial carcinoma of the lung : Immunohistochemical and ultrastructural observations and review of the literature

Epithelial-myoepithelial carcinoma is a rare low-grade malignant salivary gland neoplasm that most commonly occurs in the parotid gland but can also arise in minor salivary glands. We report a case of a primary epithelial-myoepithelial carcinoma of the lung. The patient is a 55-year-old black woman who presented with increasing shortness of breath and productive cough of at least 3 months duration. A left lower lobe endobronchial lesion was identified radiographically. Surgical resection of the lesion was performed, obtaining a circumscribed, nonencapsulated 3.9 cm tan mass which was attached to the inner wall of the lateral basal segment bronchus. A biphasic proliferation of epithelial (cytokeratin positive; S-100 protein and muscle-specific actin negative) and myoepithelial (S-100 protein and muscle-specific actin positive with focal weak cytokeratin positive) cells was identified by immunohistochemical and ultrastructural analysis of formalin-fixed tissue. The patient is disease free 7 months after resection. Pulmonary epithelial-myoepithelial carcinoma likely derives from the submucosal bronchial glands and should be added to the growing list of salivary gland-type neoplasms that may occur as primary pulmonary neoplasms. Because its histology is identical to salivary epithelial-myoepithelial carcinoma, pulmonary epithelial-myoepithelial carcinoma should be considered a low-grade malignant neoplasm and should be designated as epithelial-myoepithelial carcinoma is preference to other terms that may not convey its malignant potential. Although follow-up on reported cases is limited, lobectomy with negative bronchial margin should be curative.

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

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

Identification of titanium in human tissues: probable role in pathologic processes.

Six cases of titanium dioxide exposure involving lung, skin, and synovium are described, with a review of the literature. The patients, four men and two women, were between the ages of 22 and 65 years. The pulmonary changes were characterized by fibrosis and numerous macrophages with abundant deposition of a black pigment. Adjacent areas of bronchopneumonia were also observed. In the skin a severe necrotizing lesion involving the subcutaneous tissue with extension to the muscle was observed in one case and a nonspecific inflammatory response was observed in another; both cases showed abundant black pigment deposition. Electron microscopy and energy dispersive x-ray analysis demonstrated the presence of large quantities of titanium in the pigment granules. There may be a combination of black pigment deposition and fibrosis, necrosis, or a xanthomatous or granulomatous reaction, that, together with negative results on special staining and culture studies for organisms, should raise the suspicion of titanium-associated injury and prompt the study of the affected tissues by x-ray analysis for positive identification.

Thymic carcinoma: spectrum of differentiation and histologic types.

INTRODUCTION Primary thymic carcinomas are unusual neoplasms that have been the subject of much scrutiny in the recent literature. In particular, great attention has been focused on morphologic heterogeneity and variability in their spectrum of differentiation. Awareness of the existence of primary carcinomas of the thymus is of relatively recent vintage. Although mention of thymic epithelial neoplasms displaying cytologic features of squamous cell carcinoma had been made in the two Fascicles on Tumors of the Thymus Gland, 12 neither of these two seminal reference books specifically approached the topic. The first formal mention of thymic carcinoma was presented in a 1977 Japanese study by Shimosato et al., 3 in which the authors reported eight cases of well-differentiated squamous cell carcinoma located in the anterior mediastinum, interpreting them as being of thymic origin. A more detailed elaboration on thymic carcinoma was introduced the following year by Levine and Rosai 4 in their review article on thymic hyperplasia and neoplasia. The authors seParated thymic epithelial neoplasms into benign and malignant, with the malignant category being further subdivided into two types: (1) malignant thymoma, type I, characterized by absence of cytologic evidence of malignancy, and (2) malignant thymoma, type II, characterized by overt cytologic features of malignancy considered synonymous with thymic carcinoma. The acceptance of the concept that the thymus could be the primary seat tot the development of an overtly malignant epithelial neoplasm opened the way for the subsequent recognition of a variety of tumors that were felt to represent examples of thymic carcinomas. Thus, Shover et aL s in 1982 described five novel histologic variants of thymic carcinoma, and this was followed by a study from the Mayo Clinic, 6 which re-emphasized the histologic heterogeneity of these unusual lesions. Since then, several studies have been published addressing the clinicopathologic, immunohistochemical and ultrastructural features of these tumors, and broadening our understanding of their pathogenesis and various realized lines of differentiation.

Acinic cell carcinoma of the lung ("Fechner tumor"). A clinicopathologic, immunohistochemical, and ultrastructural study of five cases.

The clinical, pathological, immunohistochemical, and ultrastructural features in five cases of primary acinic cell carcinoma of the lung are presented. The patients ages ranged from 44 to 75 years (mean, 56); four were women and one a man. The lesions were discovered incidentally on routine chest x-ray and ranged from 1.2 to 4 cm in greatest diameter. Three tumors were located in the right middle lobe, one in the right upper lobe, and one in the left upper lobe. In three cases, the lesions presented as asymptomatic subpleural nodules in proximity to secondary bronchi, one case presented as an endobronchial tumor that led to obstructive symptoms, and one case as a well-circumscribed deep parenchymal nodule. Histologically, the tumors were composed of clear cells with abundant granular cytoplasm growing as solid sheets with focal acinar, microcystic, and papillocystic areas. Immunohistochemical stains showed strong positivity of the tumor cells for low-molecular-weight cytokeratins and epithelial membrane antigen (EMA). Focal weak cytoplasmic positivity was observed in three cases with alpha- 1-antichymotrypsin and in one case with amylase. Stains for vimentin, S-100 protein, chromogranin, and lysozyme were negative in all cases examined. Electron microscopy performed in four cases showed abundant zymogen-type cytoplasmic granules of variable electron density characteristic of acinar-type secretory cells. All patients were treated by lobectomy alone. Follow-up of 3 to 10 years in four cases revealed that all patients were alive and well, with no evidence of recurrence or metastases. Because of their relatively indolent behavior and favorable prognosis, primary acinic cell carcinoma of the lung must be distinguished from other primary and metastatic clear cell tumors of the lung.

Benign mixed tumors (pleomorphic adenomas) of the breast

Six cases of benign mixed tumors of the female breast are described. The tumors were found in three settings: (a) as a de-novo lesion arising from breast parenchyma, (b) as single or multiple nodules arising in a background of benign proliferative epithelial elements, and (c) in association with breast carcinoma. The tumors ranged from 1 to 4 cm in diameter, and were histologically characterized by the admixture in various proportions of benign glandular epithelial and myoepithelial elements and cartilaginous or myxoid components. Immunohistochemical staining supported this interpretation. One of the cases was remarkable for the presence of abundant tyrosine-like crystals, a feature described in benign mixed tumors of salivary glands. None of the tumors has recurred during a follow-up period of 1–7 years. Mixed tumors of the breast are considered to be similar to their dermal and salivary gland counterparts.

On the Histologic Heterogeneity of Thymic Epithelial Neoplasms Impact of Sampling in Subtyping and Classification of Thymomas

Six hundred thirty cases of thymomas were evaluated to determine morphologic heterogeneity. The thymomas were grouped in 4 categories using previous terminology. Stratification according to the number of sections available for examination revealed a marked difference in distribution by histopathologic type. A cutoff number of 5 sections appears to provide a difference in subgrouping these tumors. In addition, the proportion of invasive tumors increases with the number of sections examined. Final classification may be affected by the extent of sampling. Histopathologic classification of thymoma, although of academic interest, may have limited practical relevance for assessment of prognosis in limited biopsy tissue. Proper evaluation of histology and aggressive potential in thymoma should be based on ample sampling and assessment of capsular integrity, which is best accomplished on thoroughly sampled resection specimens rather than incomplete or limited biopsy samples.