Thomas V. Colby

Bronchiolitis obliterans organizing pneumonia.

In 50 of 94 patients with bronchiolitis obliterans we found no apparent cause or associated disease, and the bronchiolitis obliterans occurred with patchy organizing pneumonia. Histologic characteristics included polypoid masses of granulation tissue in lumens of small airways, alveolar ducts, and some alveoli. The fibrosis was uniform in age, suggesting that all repair had begun at the same time. The distribution was patchy, with preservation of background architecture. Clinically, there was cough or flu-like illness for 4 to 10 weeks, and crackles were heard in the lungs of 68 per cent of the patients. Radiographs showed an unusual pattern of patchy densities with a ground glass appearance in 81 per cent. Physiologically, there was restriction in 72 per cent of the patients, and 86 per cent had impaired diffusing capacity. Obstruction was limited to smokers. The mean follow-up period was four years. With corticosteroids, there was complete clinical and physiologic recovery in 65 per cent of the subjects; two died from progressive disease. This disorder differs from bronchiolitis obliterans with irreversible obstruction. It was confused most often with idiopathic pulmonary fibrosis. In view of the benign course and therapeutic response, a histologic distinction is important.

Central Nervous System Involvement in non-Hodgkin 's Lymphoma: An Analysis of 105 Cases

Records of 105 patients with central nervous system (CNS) lymphoma were analyzed in order to better define the incidence, setting, and management of CNS lymphoma and the role for CNS prophylaxis. Survival was best for patients under 30 years of age treated with whole‐brain irradiation and intrathecal (IT) chemotherapy whose CNS involvement was an isolated event (median survival time, 1.8 years). Survival was worst for patients over 30 years of age whose CNS invasion occurred at a time of progressive systemic lymphoma (median time ten weeks if treated with whole‐brain irradiation with or without IT chemotherapy). The risk of CNS invasion was greatest for those with lymphoblastic lymphoma. Among patients with Stage IIE, III, or IV histiocytic lymphoma, the risk of CNS involvement was greatest for those with progressive or relapsing disease or involvement of the testes, peripheral blood, or epidural space of the spinal cord.

Histologic conversion in the non-Hodgkin's lymphomas.

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkins lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkins lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.

Analysis of lymphoepithelioma and lymphoepithelioma-like carcinomas for Epstein-Barr viral genomes by in situ hybridization.

Lymphoepithelioma of the nasopharynx has a strong association with Epstein-Barr virus (EBV). To test the hypothesis that lymphoepithelioma-like carcinomas occurring at other sites are also associated with EBV virus, we used in situ hybridization to analyze 20 cases of lymphoepithelioma and histologically similar lesions and five basaloid squamous cell carcinomas for evidence of EBV genomes. EBV genomes were demonstrated in six of six lymphoepitheliomas of the nasopharynx but in none of five basaloid squamous cell carcinomas. Only one of 14 lymphoepithelioma-like carcinomas was found to contain EBV genomes. The single positive lymphoepithelioma-like carcinoma occurred in the lung of an Asian patient, suggesting that ethnic or geographic influences may be important in determining whether EBV is associated with these nonnasopharyngeal neoplasms. Despite their histologic similarity, most lymphoepithelioma-like carcinomas probably have a different pathogenesis from nasopharyngeal lymphoepithelioma.

Hodgkin's Disease: A clinicopathologic study of 659 cases

A large number of histologic and clinical parameters were assessed, tabulated and intercorrelated in 659 patients with Hodgkins disease evaluated and treated at Stanford University Medical Center. Nodular sclerosis was the most common pattern (60%) and also had the best total survival, but lymphocyte predominance had the best relapse‐free survival. While a number of histologic parameters showed a significant correlation with relapse‐free survival, multivariate analysis showed that age, stage, and treatment were relatively more important. Of the histologic parameters, only the number of lymphocytes, fibroblasts, and amount of sclerosis remained significant after multivariate analysis. The positive correlation of sclerosis, negative correlation of the number of fibroblasts and lack of correlation of lacunar cells with relapse free survival in patients with nodular sclerosis suggested that the type of mesenchymal reaction was of prime importance in determining prognosis in that form of Hodgkins disease. The number of lymphocytes did not independently affect prognosis in patients with nodular sclerosis but did so for the entire group. The cellular phase of nodular sclerosis was found to have an overall survival and some clinical features more akin to mixed cellularity Hodgkins disease.

Analysis of non-Hodgkin's lymphomas with nodular and favorable histologies, stages I and II

Between 1961 and 1980, 124 patients with Stages I and II nodular lymphocytic poorly differentiated (NLPD), nodular mixed histiocytic‐lymphocytic (NM), nodular histiocytic (NH), or diffuse well‐differentiated lymphocytic (DLWD) lymphoma according to the Rappaport classification were treated at Stanford University. Initial staging studies included lymphangiography in 91%, bone marrow biopsy in 93%, and diagnostic or staging laparotomy in 41% of patients. All patients were treated with megavoltage irradiation to either involved field (IF), extended field (EF), or total lymphoid fields (TLI) to a total dose of 3500–5000 rad. Median follow‐up was 5.5 years. Kaplan‐Meier actuarial survival at 5, 10, and 15 years was 84%, 68%, and 42%, respectively. Freedom from relapse at 5 and 10 years was 62% and 54%, respectively. In addition, there was a flattening of the relapse curve suggesting cure of approximately 50% of patients. Patients with NH had a significantly poorer survival (P = 0.03) while there were no differences among the other histologic groups. Freedom from relapse was higher in patients treated with TLI compared with those treated with IF or EF. However, a prospective study of 20 patients who all underwent staging laparotomy and were randomized to treatment with either IF or TLI revealed no significant difference in either survival or freedom from relapse. Utilizing multivariate analysis for the entire group, important prognostic factors included age, stage, histologic subtype, and treatment field. Cancer 52:2300‐2307, 1983.

Factors Predicting Survival in Adults with Stage I and II Large-Cell Lymphoma Treated with Primary Radiation Therapy

The records of 148 consecutive patients with Ann Arbor stage I and II large-cell lymphoma treated with primary radiation therapy with or without adjuvant chemotherapy were analyzed retrospectively for pretreatment prognostic variables and results of treatment. For patients treated with radiation to fields on one side of the diaphragm, the 5 year freedom-from-relapse rate was 25% and the survival rate was 35%, but for those given additional transdiaphragmatic radiation or for those given radiation plus adjuvant chemotherapy, the rates were both approximately 67%. In a multivariate analysis, the only significant pretreatment prognostic variables were the number of sites of involvement and bulk of disease, with relapse as the endpoint. For patients treated with radiation to both sides of the diaphragm or with radiation plus adjuvant chemotherapy, the 5-year freedom-from-relapse rate was 82% for the group with a favorable prognosis (with less than three sites of involvement and a mass size of less than 10 cm) and 55% for those with an unfavorable prognosis.

Differential diagnostic features of nodular L & H Hodgkin's disease, including progressive transformation of germinal centers

The histologic features in 171 cases of nodular lymphocyte-predominant (L&H) Hodgkins disease are presented and the association with an abnormal form of follicular hyperplasia termed “progressively transformed germinal centers” (PTGC) by Lennert is discussed. PTGC may closely resemble the nodules of L&H Hodgkins disease and in 18% of our cases the two processes coexisted in the same lymph node. In addition, two patients had lymph node biopsies showing PTGC prior to biopsies showing nodular L&H Hodgkins disease and three patients with histologically proved Hodgkins disease were found to have PTGC in subsequent lymph node biopsies. Immunologic studies on frozen tissue sections from three cases of nodular L&H Hodgkins disease showed that the neoplastic nodules contained abundant dendritic reticulum cells and B-lymphocytes with scattered T-lymphocytes. These findings suggest that the association between PTGC and nodular L&H Hodgkins disease is more than coincidental and that this form of Hodgkins disease preferentially involves B-cell areas of the lymph node, in contrast to the T-zone distribution in other forms of this disorder.

Pulmonary lymphomas simulating lymphomatoid granulomatosis

Twenty cases of malignant lymphoma presenting in the lung and 10 cases with secondary pulmonary involvement were studied. All cases shared the feature of prominent vascular infiltration by lymphoid cells, and in the 20 cases presenting with pulmonary involvement, this feature led to confusion with lymphomatoid granulomatosis. Both the primary and secondary lymphomas showed similar histologie features including vascular infiltration, extensive necrosis, and foci of a histologically polymorphous and benign infiltrate. The diagnosis of lymphoma was based on the identification of monomorphous foci of atypical lymphoid cells except in the cases of Hodgkins disease. The malignant cells were occasionally focal and microscopic and surrounded by an extensive histologically benign infiltrate. Examination of several blocks was often required in such cases before a diagnosis of lymphoma could be made. The clinical and radiologie findings at presentation were nonspecific. Radiologie findings included unilateral or bilateral nodules and infiltrates. The prognosis of the 20 patients who presented with pulmonary lymphoma was poor; half were dead in less than 2 years.

Clear cell tumor of the lung : a clinicopathologic, immunohistochemical, and ultrastructural study of eight cases

We studied eight clear cell tumors of the lung (CCTL) to better define their clinical, immunohistochemical, and ultrastructural features, and to clarify their distinction from other neoplasms, particularly metastatic renal cell carcinoma. Patients ranged in age from 31 to 67 years (mean, 51 years). Seven patients had clinically benign, asymptomatic lesions measuring less than 2 cm in diameter that were devoid of necrosis. The eight patient had a symptomatic, partially necrotic CCTL 4.5 cm in diameter that metastasized to the liver and peritoneum; the patient died of tumor 17 years after diagnosis. Ultrastructural study of seven CCTL showed interdigitating cell processes (all cases), primitive cell junctions (five of seven cases), intracytoplasmic glycogen (all cases), and rare dense core granules (two of seven cases). Immunohistochemically, paraffin-embedded sections from all eight CCTL were negative for cytokeratin (CK), epithelial membrane antigen (EMA), chromogranin, and vimentin. Focal staining was seen for S-100 protein (three of eight cases), neuronspecific enolase (three cases), synaptophysin (one case), and Leu 7 (one case). Although these findings suggest that at least some CCTL exhibit neuroendocrine differentiation, the tumors histogenesis remains uncertain. Of more practical importance, the combined absence of CK, EMA, and vimentin in formalin-fixed, paraffin-embedded CCTL virtually precludes confusion with renal cell carcinoma. Although traditionally considered bengign, CCTL larger than 2 cm that are symptomatic, and focally necrotic should be regarded as potentially as potentially malignant neoplasms.