Mary J. Matthews

CNS metastases in small cell bronchogenic carcinoma. Increasing frequency and changing pattern with lengthening survival

The records of 209 patients with small cell bronchogenic carcinoma were reviewed to define the problem of CNS metastases. CNS metastases were documented in 102 of these patients (49%) and 55 of 85 autopsied patients had CNS metastases (65%). The probability of developing a CNS metastasis increased with lengthening patient survival to a level of 80% after 2 years. As in other series, the cerebrum was the most frequently involved site. In addition, leptomeningeal, spinal, pituitary, and cerebellar metastases, and multiple sites of involvement were far more common than in previously reported series. Patients with bone marrow and liver metastases at initial staging were more likely to develop CNS metastases than those without these metastases. Bone marrow involvement was strongly associated with the development of leptomeningitis. Systemic chemotherapeutic agents which cross the blood brain barrier did not prevent the high frequency of CNS metastases. Pathologic studies suggested cerebral and leptomeningeal metastases may arise via hematogenous spread or via penetrating vessels from bone marrow to the subarachnoid space. Therapy for CNS metastases provided adequate palliation, and the majority of deaths were due to systemic rather than neurologic disease. Nevertheless, prophylactic therapy appears necessary at present to prevent the morbidity associated with these metastases. As further improvements in systemic therapy evolve, CNS prophylaxis may also be required for “cure” of patients with small cell lung cancer.

Clinical course of retrovirus-associated adult T-cell lymphoma in the United States.

We studied the clinical features of 11 patients with adult T-cell lymphoma associated with the human T-cell lymphoma virus. The patients were predominantly young, black, and born in the southeastern United States. They had an aggressive course, with the rapid onset of disseminated skin lesions or symptoms related to hypercalcemia and other metabolic disturbances, or both. Common findings included rapid enlargement of peripheral, hilar, and retroperitoneal lymph nodes, with sparing of the mediastinum; invasion of the central nervous system, lungs, or gastrointestinal tract; and opportunistic infections. A paraneoplastic syndrome characterized by increased bone turnover, abnormal bone scintigraphy, and hypercalcemia was present in all patients. Intensive combination chemotherapy produced prompt complete clinical remissions, which were generally of short duration. Similar features have been described in patients in Japan and the West Indies who had adult T-cell lymphoma, which is also associated with the human T-cell lymphoma virus. This syndrome should be suspected in patients presenting with the acute onset of widespread T-cell lymphoma in association with metabolic bone disease and hypercalcemia. The presence of the syndrome can be confirmed by appropriate serologic and virologic studies.

Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups.

STUDY OBJECTIVE To determine the optimal staging evaluation at the time of initial diagnosis of mycosis fungoides or the Sézary syndrome. DESIGN Retrospective review of a uniformly staged inception cohort. SETTING Single-institution tertiary care center. PATIENTS 152 consecutive patients who had mycosis fungoides with or without the Sézary syndrome within 6 months of the initial definitive diagnosis. INTERVENTION A detailed staging evaluation including physical examination, routine laboratory studies, chest roentgenogram, lymphangiogram, peripheral blood smear, lymph node biopsy, bone marrow aspirate or biopsy, and liver biopsy in selected patients. MEASUREMENTS AND MAIN RESULTS Univariate adverse prognostic features at initial diagnosis in patients with mycosis fungoides included (P less than 0.01) one or more cutaneous tumors or generalized erythroderma, adenopathy, blood smear involvement with Sézary cells, lymph node effacement, eosinophilia, and visceral involvement. Important, independent prognostic factors in a multivariate analysis are the presence of visceral disease and type of skin involvement. CONCLUSIONS A staging system based on histopathologic evaluation of skin, lymph nodes, blood, and visceral sites provides more comprehensive prognostic information than clinical evaluation of skin disease and adenopathy. Patients may be divided at initial presentation into three prognostic groups: good-risk patients, who have plaque-only skin disease without lymph node, blood, or visceral involvement (median survival, greater than 12 years); intermediate-risk patients, who have cutaneous tumors, erythroderma, or plaque disease with node or blood involvement but no visceral disease or node effacement (median survival, 5 years); and poor-risk patients, who have visceral involvement or node effacement (median survival, 2.5 years).

The clinical behavior of 'mixed' small cell/large cell bronchogenic carcinoma compared to 'pure' small cell subtypes

Biopsy specimens from 19 previously untreated lung cancer patients were prospectively diagnosed as small cell carcinoma with a large cell component. The patients were thoroughly staged and received intensive combination chemotherapy. They represented 12% of all small cell carcinoma cases eligible for aggressive chemotherapy protocols during a 5.5 year period. To determine whether the clinical behavior of this ‘mixed’ histologic variant differed from the other histologic subtypes of small cell lung cancer, we compared these 19 patients to a concurrent group of 103 patients with only small cell cancer in their diagnostic biopsies given equivalent therapy. The ‘mixed’ histology patients were comparable to the ‘pure’ small cell group in age, performance status, extent of disease, and frequency of bone marrow, liver, bone, and central nervous system metastases. Their complete plus partial response rate (58%) was significantly less than the response rate for the ‘pure’ small cell patients (91%), their complete response rate was also lower (16 versus 46%), and their overall survival was significantly shorter (median, 6 versus 10.5 months). Mixed histology small cell/large cell carcinoma represents a distinct pathologic variant of small cell carcinoma of the lung, associated with lower response rates and shorter survival than the ‘pure’ small cell subtypes. Since combination chemotherapy yields some complete responses and long‐term disease‐free survival in these patients, however, aggressive treatment with potentially curative intent should be considered in their management.

Prospective staging evaluation of patients with cutaneous T-cell lymphomas. Demonstration of a high frequency of extracutaneous dissemination.

A prospective pretreatment staging evaluation was done on 49 consecutive patients with mycosis fungoides or the Sézary syndrome to study patterns of disease spread and prognostic factors. Routine staging procedures included complete blood count, blood chemistries, chest roentgenogram, lymphangiogram, radionuclide scans, bone marrow aspiration and biopsy, liver biopsy, and lymph node biopsy. Special evaluations included cytogenetic analysis, electron microscopy, and T-cell cytology. Extracutaneous lymphoma was documented by light microscopy in 51% of patients and by the three special procedures in 88%. Extracutaneous lymphoma was most frequent in blood and lymph nodes; 18% of patients had visceral involvement. Patients with generalized erythroderma had a higher frequency of extracutaneous disease than did patients with cutaneous plaques and tumors by both light microscopy and special studies. Survival was directly related to the type of skin involvement and the presence or absence of extracutaneous disease. Systemic dissemination of cutaneous T-cell lymphoma is frequent, generally asymptomatic, and develops early via the circulation. These findings may explain why cutaneous therapies are associated with a high frequency of relapse.

Role of prophylactic cranial irradiation in prevention of central nervous system metastases in small cell lung cancer. Potential benefit restricted to patients with complete response

Abstract The records of 332 patients with small cell lung cancer treated on National Cancer Institute protocols between 1970 and 1980 were reviewed to evaluate the association of prophylactic cranial irradiation with the development of central nervous system metastases and survival. Stage of disease, involvement of liver, bone marrow, and bone, and the degree of response to systemic therapy were prognostic features significantly associated with the development of central nervous system metastases. Prophylactic cranial irradiation had no influence on leptomeningeal, spinal, or epidural metastases, but a significant reduction In intracerebral metastases was observed. There was also a statistically significant improvement in overall survival in patients who received prophylactic cranial irradiation (p

Cytologic transformation in cutaneous T cell lymphoma: a clinicopathologic entity associated with poor prognosis.

The clinical course of cutaneous T cell lymphoma (mycosis fungoides and Sezary syndrome) is generally indolent, but in occasional patients becomes fulminant. We found that biopsies from patients with accelerating disease can reveal cytologic transformation from previously observed small, convoluted lymphocytes to large cells that are similar to cells seen in large-cell lymphoma. The cerebriform nuclei characteristic of malignant T cells can only rarely be identified. Of 150 cutaneous T cell lymphoma patients we treated from 1976 to 1984, cytologic transformation was identified in 12 after review of peripheral blood smears and biopsies from skin, lymph nodes, and visceral sites. Patients who developed cytologic transformation were initially characterized by advanced stage (11 of 12), with lymph node effacement (seven of 11) and erythroderma (five of 12). The tumor cell DNA content after transformation was aneuploid (four of four), and the ability to form rosettes with sheep erythrocytes was retained in transformed cells (three of three). The median time from diagnosis of cutaneous T cell lymphoma to cytologic transformation was 21.5 months (range, 4 to 64), and the median survival from transformation was only 2 months (range, 0 to 19+). We conclude that cytologic transformation in cutaneous T cell lymphoma represents a distinct clinicopathologic entity, characterized by an aggressive clinical course.

Clinical implications of cytogenetic studies in cutaneous t-cell lymphoma (CTCL)

Detailed cytogenetic studies were performed in 41 patients with cutaneous T‐cell lymphoma (CTCL): four patients had limited plaques, 13 patients had generalized plaques, eight patients had cutaneous tumors, 16 patients had generalized erythroderma, and four additional patients, who had relatively benign chronic dermatosis, served as controls. Correlating the histologic and cytogenetic results in the various tissues, it was observed that 62% of the peripheral blood specimens were cytogenetically positive but only 49% were morphologically positive; in the lymph node the ratio was 80 versus 45%, and in the bone marrow, 6 versus 3%. These studies demonstrate that chromosome abnormalities are frequently detectable before morphologic changes become apparent. Chromosome banding preparations showed extensive and wide‐ranging heteroploidy; the #1 chromosome was most frequently involved in structural abnormalities while chromosomes #11, 21, and 22 were most frequently involved in numerical abnormalities. These cytogenetic findings support the impression that CTCL is a disease whose various clinical manifestations represent a chronologic sequence, with the cytogenetic findings paralleling the clinical symptoms: patients with minimal chromosomal changes had the best survival and the more extensive the chromosome abnormalities, the more advanced the clinical disease. Clone formation was seen in eight patients and this phenomenon, along with hyperdiploidy and near‐tetraploidy, was associated with a poor prognosis and short survival. We conclude that CTCL progresses from an early phase with extensive chromosomal abnormalities and lack of clone formation to a terminal phase with clone selection. Cytogenetic studies can, therefore, be of significant diagnostic and prognostic value in CTCL.

Patients with Small-Cell Lung Cancer Treated with Combination Chemotherapy with or without Irradiation: Data on Potential Cures, Chronic Toxicities, and Late Relapses After a Five- to Eleven-Year Follow-up

We assessed the outcome in 252 patients with small-cell lung cancer 5 to 11 years after treatment with combination chemotherapy, with or without chest and cranial irradiation, in National Cancer Institute therapeutic trials from 1973 through 1978. Twenty-eight patients (11%) survived free of cancer for 30 months or more. Fourteen patients remain alive without evidence of cancer beyond 5 years (range, 6.4 to 11.3 years), and 7 patients have returned to a lifestyle similar to that before diagnosis. The other 14 patients who were cancer-free at 30 months have developed cancer or died; 6 patients had a relapse, 4 developed or died from non-small-cell lung cancer, and 4 died of unrelated causes. A few patients with small-cell lung cancer (5.6%) may be cured. Thirty-month, cancer-free survival is insufficient to show a cure. Although late toxicities are troublesome, they do not outweigh the benefits of prolonged survival and potential for cure with modern aggressive therapy in small-cell lung cancer.

Portal Vein Thromboses in Malignant Hepatoma

Excerpt In one of our patients portal vein thrombosis complicating malignant hepatoma was diagnosed by splenoportography and confirmed by postmortem examination. This prompted us to review 25 cases...