Joseph C. Eggleston

Thymoma: a clinical and pathological study of 65 cases.

A clinicopathologic study of 65 patients with thymomas was performed. The most significant prognostic feature of the thymomas was the presence or absence of gross invasion of adjacent tissue. None of 37 patients with non‐invasive thymomas died of tumor or had a recurrence. Invasive thymomas resulted in the death of 3 of 17 patients. Two others are alive with unresectable tumor, and one other patient died of myasthenia gravis with recurrent thymoma. The histologic type of thymoma had no value in predicting prognosis. Thirty‐five patients had possibly associated syndromes. These syndromes, particularly myasthenia gravis and red cell hypoplasia, affected survival to an equal or greater extent than did the direct effects of the tumors.

Prognosis of Untreated Stage A1 Prostatic Carcinoma: A Study of 94 Cases with Extended Followup

Previously we showed that in cases of stage A prostatic cancer, if the tumor involved 5 per cent or less of the tissue and was not high grade (stage A1), only 2 per cent of the tumors progressed at 4 years. The current study investigated a larger group of 94 men with stage A1 disease and extended followup. While 26 men (mean age 75 years) died of other causes less than 4 years after diagnosis, of the 50 men who remained at risk 8 years or longer from the time of diagnosis 8 (16 per cent) had progression of disease. The intervals from diagnosis to progression ranged from 3.5 to 8 years, with 6 of the 8 patients dying of the cancer. Neither volume nor grade predicted progression, since of the 8 tumors that progressed 4 involved less than 1 per cent of the tissue and 6 were low grade. Based on these findings we conclude that stage A1 tumors progress at longer intervals from diagnosis and at lower frequency than stage A2 tumors. However, patients with stage A1 disease are not entirely free of risk of progression, and because 16 per cent of the men in this study who were at risk 8 years or longer experienced progression this factor must be recognized in the management of young men with stage A1 tumors.

Changes in morphologic and biochemical characteristics of small cell carcinoma of the lung. A clinicopathologic study.

Abstract Small cell carcinoma of the lung is considerably more responsive to cytotoxic chemotherapy and radiotherapy than the other histologic types of lung carcinoma. The therapeutic implications of making an accurate pathologic distinction between small cell carcinoma and other types of lung cancer stimulated this assessment of the pathologic homogeneity of small cell carcinoma. The records of 40 autopsy patients with biopsy proved small cell carcinoma seen at the The Johns Hopkins Hospital between 1970 and 1978 were reviewed. In five of the 40 patients, carcinoma (squamous carcinoma in three, adenocarcinoma in one and large cell undifferentiated carcinoma in one), but not small cell carcinoma, was seen at autopsy. Six cases were identified in which other histologic patterns of lung cancer were present in addition to the small cell carcinoma in the autopsy specimens. In order to determine whether the tumor at autopsy was biochemically as well as morphologically distinct from small cell carcinoma, histaminase and L-dopa decarboxylase activity were measured in the lung tumor and in mediastinal metastases in four cases in which no small cell carcinoma was present at autopsy. The levels of these enzymes in the tumors were markedly lower than the levels found in small cell carcinoma in previous studies. These changes in the pathologic and biochemical characteristics of these lung cancers could reflect the emergence of another tumor which was present from the outset, the development of a second tumor, differentiation of the initial tumor or an effect of cytotoxic therapy on the morphology of small cell carcinoma. Determining the exact mechanisms for these morphologic and biochemical findings may provide the basis for more rationale therapy of small cell carcinoma and also has implications for studies of the biology and histogenesis of this tumor.

Radical prostatectomy with preservation of sexual function: Pathological findings in the first 100 cases

In an effort to preserve sexual function, a nerve-sparing technique for radical retropubic prostatectomy has been used in 100 consecutive men with clinically localized prostatic cancer. Each gland was submitted for total histological examination in a way that permitted determination of the extent of the tumor and adequacy of surgical margins. Although 41 patients had established tumor in periprostatic tissue only 7 had positive surgical margins: all 7 had extensive extraprostatic involvement by tumor, while 5 had involvement of the seminal vesicles and none had surgical margins positive only at the site of the nerve-sparing modification. Sexual function was evaluated in 60 of the patients who were potent preoperatively and who have been followed for a minimum of 1 year: 84 per cent of the patients with an intact prostatic capsule were potent compared to 43 per cent with extensive involvement of periprostatic tissue and 33 per cent with involvement of the seminal vesicles or pelvic lymph nodes. Based upon our findings there is no indication that the nerve-sparing modification compromises the adequacy of the removal of the cancer, which is determined primarily by the extent of the tumor rather than the operative technique. Thus, it appears possible to preserve sexual function in a majority of patients undergoing radical prostatectomy without compromising the adequacy of the cancer operation.

Variable content of histaminase, L-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung. Biologic and clinical implications.

To ascertain whether the content of endocrine markers is constant in small-cell carcinoma of the lung, levels of three markers of medullary thyroid carcinoma were studied in this tumor. Histaminase was increased in six of six primary tumors (three to 14,000 times), L-dopa decarboxylase in four of six (six to 30 times), and calcitonin in one of one (eight times) over levels in adjacent lung. Marker levels in mediastinal metastases reflected those in primary tumors in four of five patients. However, in four of seven, multiple hepatic metastases contained low to absent levels despite simultaneously high values in chest lesions. Immunohistochemical studies of histaminase revealed that within each primary tumor different cells contained different amounts of the enzyme. Since marker content varied between tumor cells, between primary tumors and between metastases in individual patients we conclude that circulating levels of these three markers cannot be expected necessarily to mirror tumor burden in patients with small-cell lung tumors.

A New Method to Assess Metastatic Potential of Human Prostate Cancer: Relative Nuclear Roundness

A new technique has been developed that helped in an accurate prediction of the prognosis of 27 patients with stages B1 and B2 prostatic cancer following radical prostatectomy. This method involves computer-assisted image analysis of histological specimens of the primary lesion removed at the time of radical perineal prostatectomy. On the basis of a nuclear shape factor, known as nuclear roundness, we have been able to distinguish those tumors with a high metastatic potential from tumors that are less aggressive. This technique provides pathologists with quantitative information about the metastatic potential of a tumor, which may aid in the management of the individual patient.

Nuclear roundness factor. A predictor of progression in untreated stage A2 prostate cancer

A measurement of nuclear roundness involving computer‐assisted image analysis of histologic specimens was used to predict the prognosis of 19 patients with Stage A2 prostate cancer. This technique accurately identified those tumors that clinically progressed without treatment and those that did not, in contrast to the Gleason grading system, which produced significant prognostic overlap. What separated most of these tumors was the quantification and degree of irregularity of a relatively small subpopulation of cancer nuclei among a majority of rounder nuclei. There are currently several practical limitations in the use of this method, but with improvements in technique and in methods of obtaining tissue, computerized image analysis of nuclear shape may become a valuable tool for analyzing prostate cancer in a quantitative manner, thereby providing valuable information relative to the prognosis of the individual patient.

A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group.

The present randomized, prospective study was designed to assess whether alternating induction cyclophosphamide, doxorubicin, vincristine-altretamine (hexamethylmelamine), etoposide, and methotrexate (CAV-HEM) chemotherapy is better than standard chemotherapy (CAV) in improving response, survival, and remission time in 577 evaluable patients having extensive-disease small-cell lung cancer (SCLC). In addition, the study was designed to assess the impact of maintenance chemotherapy following a complete response (CR) on the time to progression and survival. The response rates (CR plus partial response [PR]) for CAV-HEM and CAV were 64% and 61%, respectively, but 23% of the patients on CAV-HEM achieved a CR compared with 16% for CAV alone (P = .03). Among complete responders, the continuation of therapy significantly increased the remission time for patients on CAV, while maintenance therapy for patients on CAV-HEM had no significant impact on remission time. However, the increased remission had little effect on survival. Patients on CAV maintenance therapy survived marginally longer than those patients on no maintenance therapy, whereas patients who received CAV-HEM and no maintenance therapy survived longer than those on maintenance therapy. CAV-HEM was associated with significantly higher severity of complications (ie, mainly myelosuppression) than CAV (P = .01). Maintenance chemotherapy was associated with significantly more complications than no maintenance therapy. Patients on CAV-HEM lived significantly longer than those on CAV alone (45.9 weeks v 42.7 weeks; P = .002). Ten percent of patients treated on CAV-HEM survived at least 2 years, compared with 4% on CAV alone. In our study involving patients with extensive-disease SCLC, the alternating induction chemotherapy significantly increased the CR rates and had a small impact on long-term survival compared with the results achieved with standard induction chemotherapy. Moreover, when the alternating induction chemotherapy was used, long-term maintenance chemotherapy was not needed.

Intravascular bronchiolo-alveolar tumor (IVBAT). A low-grade sclerosing epithelioid angiosarcoma of lung

Intravascular bronchiole-alveolar tumor (IVBAT) is a rare and highly distinctive pulmonary tumor of disputed cellular nature. Both epithelial and endothclial differentiation of this neoplasm have been suggested. We have studied multiple nodules of IVBATs from three patients by light and electron microscopy and by immunohistochemical methods for Factor VIII-related antigen (FVIII RAG). Our light and ultrastructural studies are in essential agreement with the previous suggestion of the cndothelial nature of the neoplasm and our demonstration of the presence of FVIII RAG in many of the tumor cells offers new evidence strongly supportive of their endothelial differentiation. We believe that IVBAT and a group of cxtrapulmonary tumors described as epithelioid hcmangiocndothclioma and endovascular papillary angioendothelioma are similar biologically indolent neoplasms of epithelioid and dendritic cndothelial cells characterized by stromal sclerosis, intravascular spread, a low incidence of metastases and slow clinical evolution. Thus, we regard IVBAT as a low-grade sclerosing angiosarcoma of the lung.

Relationship of lysozyme (muramidase) to histiocytic differentiation in malignant histiocytosis an immunohistochemical study

Malignant histiocytosis (MH) is a rare, usually fatal systemic disease considered to be a neoplasm of true histiocytes. Because MH may be difficult to differentiate from non‐Hodgkins lymphomas or carcinoma, we examined surgical and autopsy material from 10 patients with MH using the immunoperoxidase technique to determine if the presence of intracellular lysozyme is helpful in making this distinction. The cases of MH were divided into three groups based on the degree of cytologic atypia and the amount of phagocytic activity of the neoplastic cells: group I—minimal cytologic atypia and rare erythrophagocytosis; group II—minimal cytologic atypia with extensive erythrophagocytosis: group III—moderate to marked cytologic atypia and rare phagocytosis. Moderate to strong staining for lysozyme was observed in the neoplastic cells of group I, weak or absent staining in group II cells, and no staining in group III cells. These findings suggest the loss of detectable enzyme in poorly differentiated or dedifferentiated neoplastic histiocytes. Consideration must be given to these observations in evaluating the use of lysozyme as a possible serum or tissue aid to the diagnosis of MH.