Philip H. Lieberman

Lobular carcinoma in situ of the breast Detailed analysis of 99 patients with average follow-up of 24 years

Ninety-nine patients with in situ lobular carcinoma (LCIS) of the breast, not treated by mastectomy, were identified in a review of consecutive breast biopsies performed at Memorial Hospital between 1940 and 1950. Follow-up for an average of 24 years was obtained in order to determine the frequency of subsequent breast carcinoma. Detailed analysis of important clinical and pathologic features was undertaken to identify predictive factors that would serve to distinguish between patients with the greatest and least risk for subsequent carcinoma. Thirty-nine breast carcinomas other than the original LCIS were diagnosed in 32 patients. Half of the carcinomas occurred in the same and half in the opposite breast. The hazard rate for subsequent carcinoma increased with increasing length of follow-up and increasing age.When compared with general population data, the frequency of subsequent breast carcinoma was nine times greater than expected and deaths due to breast carcinoma were 11 times more frequent than expected. None of the currently recommended choices for therapy is entirely satisfactory. Follow-up without further surgery should be considered an investigative procedure until more information is available. This recommendation should be made only if the patient and physician are prepared to accept the responsibility of lifetime surveillance. At present, we consider it prudent in most cases to recommend ipsilateral mastectomy with low axillary dissection and concurrent biopsy of the opposite breast. Contralateral mastectomy is most appropriate when carcinoma is detected in the biopsy.

Primary gastrointestinal lymphoma: A 30‐year review

The authors reviewed all cases of non‐Hodgkins lymphoma primarily involving the gastrointestinal tract treated at Memorial Hospital during the period from 1949–1978. Complete clinical records were available in 104 cases. Slides of original pathology specimens were available in 81 cases. Tumors were classified by Rappaport, Lukes‐Collins and modified Kiel classifications. All patients were staged retrospectively, using modified Ann Arbor staging. The primary tumor was in the stomach in 76 patients, in the small bowel in 15 and in the large bowel in 13. The life‐table survival for all patients at five years was 44% and for the 81 Stage I and II patients it was 53%. We found a trend toward improved survival for patients treated in the last decade (P = 0.05). Using Cox regression analysis, survival was found to be correlated with stage (P < 0.0001) and involvement of adjacent structures (P = 0.007). For Stage I patients, resection and radiation therapy were equally effective alone in controlling local tumor even though factors responsible for the selection of either treatment could not be identified. For Stage II patients, resection combined with radiation therapy controlled local disease better than either treatment alone. For Stage II, patient survival was correlated with the pattern of nodal involvement (P < 0.0001). Neither the choice of treatment (resection, radiation therapy, or resection with radiation therapy; P = 0.17) nor the involvement of resected margins (P = 0.22) affected survival. Among 81 Stage I and II patients, 68% had recurrences outside the primary field of treatment and 60% outside the abdomen. Systemic multiple modality therapy should be considered for patients at high risk for recurrence.

Non‐Hodgkin's lymphoma in children. A comparative study of two modalities of therapy

Eighty‐six children with non‐Hodgkins lymphoma were studied from 1964 to January 31, 1975. Seventy‐six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaports diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy‐six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty‐one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1–2 months from onset of therapy.

Angiosarcoma and other vascular tumors of the breast.

Vascular tumors of the breast, with the exception of perilobular hemangiomas, are generally considered to be malignant. The pathologic and clinical features of 40 patients with angiosarcoma of the breast and 12 with other vascular tumors of the breast were reviewed. Three general histologic patterns of growth were identified among the angiosarcomas and were found to correlate closely with prognosis. Whereas 10 of the 13 patients in histologic Group I were alive and free of disease with an average follow-up of nearly 6 years, only two of 16 Group III patients were free of disease, and 14 have died. The six Group II patients had a survival similar to those in Group I. In this series the disease-free survival at 3 years was 41% and at 5 years 33%, much better than that reported in previous reviews of mammary angiosarcoma. The data also indicated that adjuvant chemotherapy, specifically actinomycin D, is effective in some and possibly all patients with angiosarcoma of the breast. The 12 other vascular lesions had distinctly different morphologic features, a benign clinical course, and should probably not be viewed as angiosarcomas. However, total excision of all vascular lesions of the breast is essential in order to determine both the diagnosis and the appropriate therapy.

Incidence of cancer in 98 patients with common varied immunodeficiency

Ninety-eight patients with common varied immunodeficiency have been observed for periods of 1–13 years. In 1986, 78 were alive, 19 had died, and 1 could not be located. Eleven patients in the group had developed cancer; two patients had had two cancers. Of the total number of neoplastic malignancies, seven were non-Hodgkins lymphoma, one patient had a Waldenstroms macroglobulinemia, and nine of the patients who developed cancer were female. Cancer developed in the fifth or sixth decade of life for 10 of the 11 patients. These data show an 8- to 13-fold increase in cancer in general for patients who have this immunodeficiency and a 438-fold increase in lymphoma for females.

Extracranial primitive neuroectodermal tumors. The memorial sloan‐kettering cancer center experience

The clinical data of 54 patients (57% males) with extracranial primitive neuroectodermal tumors (PNET) seen over a 20‐year period at Memorial Sloan‐Kettering Cancer Center were reviewed. The age at diagnosis ranged from 1 month to 81 years (median, 17 years). One PNET arose in a previously irradiated site. One patient had an unaffected identical twin. Primary sites were thoracopulmonary (n = 25), pelvis (n = 12), retroperitoneum or abdomen (n = 10), limbs (n = 5), neck (n = 1), and unknown (n = 1). At diagnosis, epidural extension was present in 13 patients with truncal primaries, and 11 patients had distant metastases. All of the latter died with disease. Progression‐free survival (PFS) among the 43 patients with localized tumors (all >5 cm) was 25% at 24 months. Two of 13 patients who relapsed after more than 12 months without therapy were long‐term survivors. Patients with localized PNET who had resection of all gross disease within 3 months of diagnosis had a significantly longer PFS (P = 0.0003). Radiation therapy caused tumor shrinkage but was not curative of measurable disease. A doseresponse effect was evident with the most commonly used drug, cyclophosphamide. Myeloablative regimens using melphalan (n = 8) or thiotepa (n = 1) with autologous bone marrow rescue were not clearly beneficial. The treatment results favor: (1) early surgical removal, (2) dose‐intensive use of drugs active against PNET (especially cyclophosphamide), and (3) radiation therapy to ablate residual microscopic disease.

Primary pulmonary lymphomas. A clinicopathologic analysis of 36 cases

The clinical and pathologic findings in 36 patients with primary pulmonary non‐Hodgkins lymphoma were retrospectively evaluated. Each lymphoma was classified according to the Rappaport, Lukes‐Collins, Working Formulation, and Kiel criteria. Twenty‐one (58%) of the 36 patients had lymphomas classified as lymphoplasmacytic/lymphoplasmacytoid type of LP immunocytoma (LPI) according to the Kiel classification. The remainder of the patients (42%) had lymphomas distributed among the follicular center cell (FCC) types and immunoblastic sarcoma in the Lukes‐Collins classification. Survival of patients with LPI was significantly longer than that of patients with other types of lymphoma (88% versus 47% 5‐year actuarial survival estimate), and the LPIs were more often confined to the lung without hilar or mediastinal lymph node involvement. Seven (33%) of the 21 LPI evantually recurred after a mean follow‐up of 69 months, and 4 of these 7 developed serum paraproteins. Most of the patients with lymphomas other than LPI had persistent disease or an early recurrence. LPI, as described by Lennert, seems prone to arise in extranodal sites and to recur late. Measurement of serum immunoglobulins may be helpful in detecting recurrences of LPI.

Multidisciplinary treatment of embryonal rhabdomyosarcoma in children

Twenty‐nine children under 15 years of age with embryonal rhabdomyosarcoma were treated according to a multidisciplinary protocol (T‐2). The protocol consisted of surgical removal of the tumor if possible, followed by chemotherapy, and also with radiation therapy in patients with gross or microscopic residual disease. Radiation therapy was given in the 4500–7000 rads range. The chemotherapy consisted of cycles of sequential administration of dactinomycin, Adriamycin, vincristine, and cyclophosphamide, with obligatory periods of rest. The drug therapy was continued for 2 years. Following surgery, clinicopathologic staging of the disease revealed 10 patients with no residual disease (I‐A), 5 with microscopic residual disease (I‐B), 5 with unresectable tumors (II), 6 with unresectable tumors plus regional lymph node involvement (III), and 3 with disseminated tumors (IV). Twenty‐four (82%) of the patients (20 Stages I‐II, 4 Stage III) are alive with no evidence of disease for 4+ to 42+ months. These results are superior to those achieved between 1960–1970 among 108 children treated at Memorial Sloan‐Kettering Cancer Center.

Mucinous adenocarcinoma of the prostate gland.

Mutinous adenocarcinoma of the prostate gland is one of the least common morphologic variants of prostatic carcinoma. A lack of precision in the definition of these mucinous neoplasms has resulted in reports which have overstated the incidence of this lesion. Of approximately 1,600 carcinomas of the prostate gland seen at Memorial Hospital from 1963 to 1983, excluding cases with only needle biopsy material, six mucinous prostatic adenocarcinomas were identified. Mucinous prostatic carcinomas were diagnosed when at least 25% of the resected tumor contained lakes of extracellular mucin, and an extraprostatic tumor site was ruled out. In five of the six cases, a cribriform pattern predominated in the mucinous areas. All of the mucinous prostatic tumors had prostate-specific acid phosphatase (PSAP) and prostate-specific antigen (PSA) immunoreactivity. Our experience and our review of the literature indicate that these tumors do not respond well to hormonal therapy. Contrary to prevalent opinion, they have an aggressive biologic behavior and, like nonmucinous prostate carcinomas, have a propensity to develop bone metastases and increased serum acid phosphatase levels with advanced disease

Extra-adrenal paragangliomas of the retroperitoneum: A clinicopathologic study of 12 tumors

ABSTRACTThe clinical and pathologic features of 12 extra-adrenal paragangliomas of the retroperitoneum are presented. The patients (eight men, four women) had an average age of 43 years at the time of diagnosis; three had symptoms related to excess catecholamine secretion. Complete surgical resection was attempted in each case but was possible for only four patients. Five tumors were malignant; four patients died from regional and/or distant metastases 17 months to 10 years after surgery. One patient was alive with metastatic paraganglioma 25 years after initial treatment. Each patient with metastatic or locally recurrent paraganglioma had incomplete resection of the primary tumor. An important microscopic feature of each paraganglioma was the presence of cytoplasmic argyrophilia. Three of the five metastasizing paragangliomas showed readily identifiable mitoses or evidence of vascular invasion; the two other cases and all of the benign tumors lacked these features. Our findings suggest that in some cases histology may prove helpful in evaluating the malignant potential of these tumors.