Alka Palekar

Pathologic findings from the national surgical adjuvant breast project (protocol no. 4). V. significance of axillary nodal micro- and macrometastases

Two‐hundred seventy eight of 565 patients treated by radical mastectomy for invasive breast cancer in a prospective, randomized clinical trial exhibited axillary nodal metastases. Patients in whom the largest nodal metastasis measured ≤2 mm in its greatest diameter were regarded as having micrometastases and those in whom the lesions were ≤2 mm as having macrometastases. Contingency table analysis disclosed that the group with macrometastases had a greater likelihood that they would be clinically assessed as stage II, their primary tumors would be ≤2 cm, they would have 4 or more positive nodes, extension of the metastasis through the nodal capsule would have occurred and uninvolved nodes would exhibit a germinal center predominance pattern. Life table analyses failed to reveal any significant difference in survival between patients with micrometastases and those without nodal metastases although both of these groups exhibited significantly greater survival than patients with macrometastases. On the other hand, treatment failure rates were more comparable in patients with micrometastases to those with macrometastases rather than absent nodal involvement. Multivariate analysis revealed that these apparent effects on survival and treatment failure rates in patients with micro and macrometastases were more directly related to the number of nodes involved with metastases rather than the size of the latter. A subset of patients with micrometastases in whom the metastases measured ≥1.3 mm was identified who exhibited survival and treatment failure rates similar to those of the negative node patients. The data, although based on a relatively small sample size, suggest metastases ≥1.3 mm may exert an influence independent of number of nodes involved. The excellent prognosis of patients with these occult nodal metastases (≥1.3 mm) warrants the designation of the stage of their disease as 1 1/2. Cancer 42:2032–2038, 1978.

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17. Five-year observations concerning lobular carcinoma in situ.

Extant information reveals inconsistencies concerning the natural history, pathologic features, and treatment of lobular carcinoma in situ (LCIS) of the breast. It is uncertain whether these are related to the methods of study, diagnostic criteria employed, relative paucity of cases, or varying lengths of follow‐up.

Mucoepidermoid and squamous cell carcinomas of breast with reference to squamous metaplasia and giant cell tumors

Clinical and pathologic features of five low-grade mucoepidermoid and a similar number of squamous cell carcinomas of breast are presented. Three of each were retrieved from 55 cases of invasive breast cancer previously assessed to exhibit squamous metaplasia. Although the estimated incidence of low-grade mucoepidermoid cancers is approximately 0.2%, they may be more frequent, masquerading under designations of squamous metaplasia or intracystic carcinomas. All patients with low-grade mucoepidermoid cancer, and the two recorded previously, were free of recurrence for 4–10 years. No high-grade mucoepidermoid cancers were found. Squamous cell cancers frequently have a phyllode configuration (carcinoma phyllodes). Two examined by electron microscopy revealed a commonality of ultra-structural features with similar tumors of other sites. None exhibited glandular differentiation or tinctorial evidence of mucin secretion. One squamous cell carcinoma contained both malignant epithelial and banal, osteo-clast-like, stromal giant cells. Only the latter were identified in tissue culture. This experience and review of the literature prompted a nosologic characterization of giant cell lesions of breast. One patient with squamous cell carcinoma succumbed because of her disease; the remainder are either free of or alive with recurrence at 4 and 10 years.

Scar cancers: Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol No. 4) — IX

SummaryThe uncomplicated non-encapsulated sclerosing lesion (NESL) or radial scar of breast is a banal lesion which may be confused with tubular carcinoma. Yet, that the latter may arise in such scars is strongly suggested by the recognition of examples portraying morphologic features consistent with such ‘early’ transformation. Further, 38% of 1569 cases of unequivocal invasive breast cancers from patients enrolled in the National Surgical Adjuvant Breast Project, protocol 4, were found to be associated with scar. The scar in 14% of these was strikingly similar if not identical morphologically with the NESL or radial scar (type l scar cancer). Four other types of scar were identified. It is uncertain whether these represent variations of the NESL or are unique. However, each type possessed some distinguishing pathologic characteristics as disclosed by contingency table analyses of 36 histopathologic and 6 clinical features of these cancers. Most importantly, 6-year postmastectomy survival was significantly better as revealed by life-table analyses for patients whose cancers were designated as types 1 and 4 than for those with other scar types or in whom their cancer lacked scar. This relationship was found to be independent of nodal status.Ductal obliteration, a common finding in the banal NESL and scar cancers, has been previously suggested to play a role in their evolution. Our observations indicate that vascular obliterative alterations may be equally or perhaps even more significant in this regard. This as well as other features suggests an analogy between them and so-called scar cancers of the lung.Attention is directed to the prognostic significance of type and degree of tubule formation observed in some breast cancers. The results suggest a revision of the scheme utilized for the histologic grading of breast cancers. However, it appears valid to simply categorize breast cancer into well-differentiated (histologic grades 1 and 2) and poorly differentiated (histologic grade 3) types.Our data does not support the hypothesis that tubular cancer may ‘progress’ into less differentiated forms.

Pseudolymphoma of breast

A lymphoid infiltrate in the breast of a 77‐year‐old woman exhibited histological features warranting a diagnosis of pseudolymphoma. Detection of surface markers on cell suspensions of the lesion revealed approximately equal numbers of B and T cells and k and γ light chains in the immunoglobulins of the former. This represents ancillary evidence that is consonant with the pseudolymphomatous nature of the infiltration. Recognition of pseudolymphoma of the breast as an entity appears significant from practical and theoretical standpoints and is relevant to considerations concerning the incidence of so‐called primary lymphoma of this organ.

Pathobiology of small invasive breast cancers without metastases (T1a/b, N0, M0): National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-21.

Uncertainties continue to exist concerning the outcomes and management of small (T1a/b N0 M0) invasive breast cancers.

Malignant granular cell tumor of the ulnar nerve with novel cytogenetic and molecular genetic findings

We report an unusual case of ulnar nerve-based malignant granular cell tumor characterized by gains of chromosome 10 and loss of P16 detected by conventional karyotyping and by fluorescence in situ hybridization, respectively, in a 74-year-old male. To our knowledge, these findings have never been reported previously in malignant granular cell tumors.

Mucocele-like Lesions and Mucinous Carcinoma of the Breast

Clinical and pathologic features of 12 examples of so-called mucocele-like lesion, mucocele-like tumor, or intraductal carcinoma with mucous leakage are recounted. Similar alterations were noted in almost one half of the pure mucinous cancers and one fifth of mixed-mucinous cancers examined. This suggests that these lesions, particularly those characterized by mucinous intraductal cancer, may represent a histogenetic spec trum with overt mucinous cancers, even though all patients in this and other studies have remained disease-free for varying periods of observation. Although overall sur vival for pure mucinous cancers was only 58% at 15 years, it was still better than that (33%) found for women of the same cohort with not otherwise specified carcinomas. There are no contraindications to treat all mammary mucinous lesions conservatively. Int J Surg Pathol 1(4):213-220, 1994

Ossifying fibromyxoid tumor: a study of 6 cases of atypical and malignant variants

Ossifying fibromyxoid tumors (OFMT) of soft parts are rare, slow-growing tumors that have potential for local recurrence and may metastasize. While OFMT originally was considered benign, several cases of malignant OFMT have been documented. There is no universally accepted risk stratification, although this study emphasizes the importance of utilizing histology, immunohistochemistry and FISH in establishing the diagnosis. Herein, we describe six cases of atypical and malignant OFMT with differences in morphologic features, 5 of which display the proposed morphological criteria for malignancy. The patients were mostly male (M=5, F=1) with an age range of 33-69 years. The tumors arose from the extremities (3 cases), the shoulder (1 case), the head and neck area (1 case), and the paraspinal area (1 case). One tumor had high grade and overtly sarcomatous changes, while another invaded the underlying clavicle. Two cases showed cytological atypia and necrosis. Fluorescence in situ hybridization (FISH) detected rearrangement of the PHF1 gene in 5 cases. All cases were positive for EAAT4 and actin by immunohistochemistry, while negative for desmin. Three tumors were immunoreactive for S100 protein. INI-1 immunohistochemical staining was conserved in all but 2 cases in which a mosaic loss of expression was noted. All but two patients are currently alive and free of disease.

Human Immunodeficiency Virus-associated primary effusion lymphoma: An exceedingly rare entity in cerebrospinal fluid.

Primary effusion lymphoma (PEL) in patients with Human Immunodeficiency Virus (HIV) infection may involve pleural, pericardial, and peritoneal cavities. PEL involving the cerebrospinal fluid (CSF) is exceedingly rare, and to our knowledge has only been reported in two cases. We report another case of PEL diagnosed in CSF from a 61-year-old male with Acquired Immunodeficiency Syndrome that presented with neurological symptoms. Imaging studies of his brain showed leptomeningeal/periventricular enhancement, but no mass lesion. His CSF demonstrated human herpesvirus-8 positive pleomorphic lymphoplasmacytoid cells of null cell phenotype. This case highlights that albeit rare, PEL should be included in the differential diagnosis when large atypical cells are encountered in CSF of HIV-positive patients, even when such patients have no history of lymphoma. As in this case, ancillary studies are required to make an accurate diagnosis of PEL in CSF cytology.