Epstein-Barr virus and lymphoproliferation in methotrexate-treated rheumatoid arthritis.

Generalized lymphadenopathy developed in a 60-year-old female receiving methotrexate and prednisone for treatment of rheumatoid arthritis. Histologic examination of an enlarged right axillary lymph node revealed effacement of normal architecture by a polymorphic population of lymphocytes. The recognition that the patient was medically immunosuppressed and the similarity of lymph node histology to that of a polymorphic post-transplantation lymphoid proliferation led to suspicion that the adenopathy might represent an immunosuppression-related lymphoid proliferation. This possibility was supported by regression of the adenopathy on discontinuation of methotrexate, despite continued corticosteroid therapy, which is an outcome reminiscent of the remissions observed with reduction of immunosuppressive therapy in post-transplantation lymphoproliferative disorders. Subsequent ancillary laboratory studies of lymph node tissue included genetic probe analysis, which revealed a monoclonal population of B-lymphocytes containing clonal Epstein-Barr virus DNA. In situ hybridization studies performed on lymph node tissue revealed expression of Epstein-Barr virus-encoded RNA 1 transcripts, and immunohistochemical studies revealed expression of Epstein-Barr virus latent membrane protein 1. These ancillary studies confirmed the similarity to post-transplantation lymphoproliferative disorder. Although immunosuppression-related lymphoproliferative disorders share features with malignant lymphoma, the possibility of resolution in situations in which immunosuppression can be reversed provides a distinction from true malignancy and is of profound importance in therapeutic decision making.

Clinical and histologic classification of endometriomas. Implications for a mechanism of pathogenesis.

One hundred eighty-seven consecutive patients with persistent ovarian cysts and endometriosis underwent laparoscopic evaluation and ovarian cystectomy. All patients had been followed for a minimum of 6 weeks prior to surgery. The cysts were identified initially to be endometriomas based on their gross appearance and the presence of endometriosis at other pelvic sites. Presumed endometriomas were classified into three types based on size, cyst contents, ease of removal of the capsule, adhesions of the cyst to other structures and location of superficial endometrial implants relative to the cyst wall. After clinical laparoscopic classification, the cysts were evaluated histologically without knowledge of the clinical assessment. Histologically small (< 2 cm), superficial ovarian cysts were always endometriomas, and the cyst wall was very difficult to remove (type I). Large cysts with easily removed walls were usually luteal cysts (type II). Large cysts with walls adherent in multiple areas adjacent to superficial endometriosis were generally endometriomas but some also had histologic characteristics of functional (luteal or follicular) cysts (types IIIa and IIIb). These findings led to the conclusion that superficial ovarian endometriosis is similar to endometriosis in extra-ovarian sites in that the formation of superficial cysts is limited in size by fibrosis and scarring. In contrast, large endometriomas may develop as a result of secondary involvement of functional ovarian cysts by the endometriotic process.

Prognostic factors in surgically resected limited-stage, nonsmall cell carcinoma of the lung.

The gross pathological, microscopic, and clinical features of 173 Stage I and Stage II primary nonsmall cell carcinomas resected for cure by segmental resection, lobectomy, or pneumonectomy at the Johns Hopkins Hospital were analyzed to determine which provided useful independent prognostic information. The tumors studied included 79 squamous carcinomas (56%); 74 adenocarcinomas (44%), including 15 undifferentiated tumors which contained intracellular mucin; 18 large-cell undifferentiated carcinomas (10%); one giant cell carcinoma (less than 1%); and one adenosquamous carcinoma (less than 1%). Clinical features evaluated for each case included age, sex, race, and history of previous or subsequent malignancy; and pathologic features evaluated included tumor size, lymph node metastases, tumor location, cellular anaplasia, desmoplastic response, inflammatory response, preexisting scar, tumor necrosis, and degree of tumor differentiation. Multivariate analysis using the Cox life table regression model indicated that five features had a significant (p less than 0.05) independent association with subsequent death due to the tumor, and that the final set was highly significant (p = 0.001). These features were the following: large-cell undifferentiated histology, lymph node metastases expressed as N classification, tumor size expressed as T classification, tumor giant cells in any histologic type, and absent or minimal plasma cell infiltration. No additional prognostic information was obtained from any of the other features analyzed.

Carcinoma of the esophagus with adenoid cystic differentiation.

Adenoid cystic carcinoma of the esophagus is a relatively rare lesion which characteristically exhibits a clinically aggressive behavior. In spite of this aggressive nature, it is most often referred to as a counterpart of the more common adenoid cystic carcinoma of salivary gland origin, a comparatively indolent tumor. In this report, the clinical and pathologic findings in a series of six cases of esophageal adenoid cystic carcinomas are contrasted with those of typical salivary gland lesions, and also compared to similar tumors exhibiting "adenoid cystic" differentiation arising in other extrasalivary gland sites. It is concluded that the esophageal tumors, as well as certain similar lesions arising in other extrasalivary gland sites, represent a class of poorly differentiated basaloid neoplasms distinct both clinically and morphologically from the common adenoid cystic carcinoma of salivary gland origin.