Arthur K.C. Lee

bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas

The bcl-2 gene is an oncogene that inhibits programmed cell death (apoptosis). We investigated by immunocytochemistry bcl-2 expression in normal colonic mucosa, hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. The purpose of the investigation was twofold; to assess the possible role of bcl-2 in colorectal tumorigenesis and to evaluate its clinical significance. The cases studied included 24 hyperplastic polyps, 49 adenomas, and 205 colorectal carcinomas. In both normal mucosa and hyperplastic polyps bcl-2 immunoreactivity was detected only in the proliferative cells of the colonic crypts. Conversely, bcl-2 immunoreactivity was noted in all adenomas irrespective of the degree of dysplastic change; it was diffuse in 84% of adenomas and focal in the remaining cases. In colorectal carcinomas bcl-2 expression was undetectable in 50% and focal (less than 50% immunostained neoplastic cells) in 38% of tumors. The remaining 12% of the carcinomas displayed diffuse (more than 50% immunostained neoplastic cells) bcl-2 immunoreactivity. In colorectal carcinomas bcl-2 expression was not correlated with relevant clinicopathologic parameters, including disease stage, tumor location and growth fraction, DNA ploidy, and p53 protein accumulation, and had no prognostic significance by univariate or multivariate analysis. These results suggest that bcl-2 oncoprotein may play a role in colorectal tumorigenesis, probably in the early phases of the adenoma-carcinoma sequence. bcl-2 expression in established tumors has no prognostic significance.

Abnormal p53 immunoreactivity and prognosis in node-negative breast carcinomas with long-term follow-up

The expression of thep53 gene product was investigated immunocytochemically in a retrospective series of 164 formalin-fixed paraffin-embedded invasive breast carcinomas with pathologically proven negative lymph nodes. Overall, 78 tumors (48%) showed a variable degree ofp53 immunoreactivity. Among these, 38 cases were low expressors (1–10%p53 immunoreactive tumor cells), 21 moderate expressors (10–50% immunoreactive cells) and 19 high expressors (> 50% immunoreactive cells). Abnormalp53 expression correlated significantly with tumor size, histological and nuclear grade, DNA ploidy, mitotic rate and proliferation index, and with the lack of estrogen receptors. Disease-free and adjusted survival analysis of the 124 node-negative patients with long term (more than 10 years) follow-up, however, did not reveal an independent prognostic role for p53 expression. These data suggest that the evaluation ofp53 immunoreactivity may only play a role in a multiparametric prognostic assessment of node-negative breast carcinoma.

Primary Histiocytic Lymphoma of the Central Nervous System: A Neoplasm Frequently Overshadowed by a Prominent Inflammatory Component

True histiocytic lymphoma, as defined by strict criteria, is a very rare neoplasm. We describe three cases occurring as primary tumors in the central nervous system. The patients, two females and one male, ranged in age from 11 to 69 years. The tumors involved the brain in two cases and spinal cord in one, with a size ranging from 7 to 17 mm. Two patients died at 4 months and 8 months, respectively, and one was alive with disease at 5 months. Pathologically, the tumors comprised groups and sheets of noncohesive large cells with pleomorphic vesicular nuclei, distinct nucleoli, and abundant eosinophilic cytoplasm. A dense inflammatory infiltrate consisting of neutrophils, lymphocytes, plasma cells, and histiocytes was present, with multiple foci of necrosis and abscess formation. All three cases demonstrated an identical immunophenotype: positive for CD68 and lysozyme; focally positive for S-100 protein, CD45RB, and CD4; and negative for CD3, CD20, CD21/CD35, CD1a, CD30, ALK1, myeloperoxidase, glial fibrillary acidic protein, and cytokeratin. The proliferative index ranged from 20% to 35%. Ultrastructural examination further confirmed the histiocytic nature of the tumor cells, characterized by irregularly folded or multisegmented nuclei and abundant cytoplasm containing lysosomes; Birbeck granules, interdigitating cell processes, and cell junctions were not found. Although the presence of abundant inflammatory cells could obscure the neoplastic histiocytes, making the distinction from inflammatory conditions difficult, awareness of this unusual histologic feature and the invariable finding of pleomorphic cells in some areas of the lesion permit the correct diagnosis to be made.

Alpha-lactalbumin as an immunohistochemical marker for metastatic breast carcinomas

Alpha-lactalbumin (ALA), a milk protein, was demonstrated by immunohistochemistry with polyclonal antisera from three different sources in primary and metastatic breast carcinomas, and mammary Pagets disease. ALA localization was observed in 67% of mammary carcinomas, and in 62% of their metastases to sites which included lymph nodes, lung, bone, liver, pericardium, skin, and subcutaneous tissue. There was close correlation between primary and metastatic breast carcinomas in ALA positivity, but no correlation between ALA positivity and histologic differentiation. A variety of nonmammary neoplasms were examined for ALA immunoreactivity. In contrast to ALA immunoreactivity of breast tissue, which was removed by preabsorption of antiserum with ALA antigen, a number of skin appendage tumors, salivary gland tumors, and mesotheliomas demonstrated positive staining which was not abolished by preabsorption and was most likely due to the presence of cross-reacting antibodies. One commercial ALA antiserum also reacted with pancreatic islet cells in a distribution similar to glucagon. Our results demonstrate the presence of ALA in breast carcinomas and its potential value to the surgical pathologist in the workup of metastatic carcinomas of unknown primary sites. However, the staining encountered in some nonmammary tumors necessitates caution in its interpretation.

MRI appearances of an ectopic pituitary adenoma: case report and review of the literature

MR images of an ectopic pituitary adenoma have been published in only a single case, a suprasellar mass. We present a patient with Cushings disease in whom MRI revealed a pituitary adenoma within the sphenoid sinus. Radiologic characteristics of ectopic pituitary adenomas are reviewed, with emphasis on MRI, which demonstrates a soft tissue mass, isointense with gray matter on T1-weighted images, which enhances in a heterogeneous manner.

Lymphatic and blood vessel invasion in breast carcinoma: A useful prognostic indicator?

Recent studies have presented compelling evidence to support the prognostic importance of peritumoral lymphatic and blood vessel invasion in breast cancer. This parameter appears to be particularly valuable in the hands of pathologists who are experienced in diseases of the breast and who have developed standardized criteria and expertise in their recognition. However, its application is seriously hampered by various factors, especially interobserver and intraobserver differences in interpretation. A more uniform and objective approach, such as the use of immunohistochemical techniques, may be helpful in overcoming these obstacles. This may render lymphatic and blood vessel invasion a reliably reproducible indicator that a practicing pathologist can utilize to recognize high-risk patients and recommend appropriate therapy. The extension of this approach to evaluate neoplasms of other organs--such as malignant melanomas and thyroid, uterine, and cervical carcinomas--should also be explored.

DNA flow cytometric analysis and prognosis of axillary lymph node-negative breast carcinoma

Methods. The prognostic significance of flow cytometric analysis in patients with node‐negative invasive breast carcinoma was evaluated in a retrospective series of 158 patients with a minimum follow‐up study of 9 years.

Intramammary lymphatic invasion in breast carcinomas: evaluation using ABH isoantigens as endothelial markers

Recent studies indicate that intramammary lymphatic invasion represents an important prognostic parameter in breast carcinomas. However, the identification of intramammary lymphatic invasion in tissue sections is a subjective procedure, frequently hampered by factors such as fixation artefacts and interobserver variations. In this study, monoclonal antibodies to ABH isoantigens were applied on formalin-fixed, paraffin-embedded breast carcinoma tissue by using the avidin-biotin-peroxidase complex technique. In addition, the H antigen was localized using the Ulex europeus agglutinin I lectin binding technique. Isoantigen localization provided excellent delineation of lymphatics and blood vessels, in general unhampered by the retention of isoantigen expression in some breast carcinomas. In comparison, Factor VIII-related antigen localization required prior trypsin enhancement and was less sensitive and less consistent. The staining for isoantigens was more intense in vascular than in lymphatic endothelium. ABH isoantigen localization of lymphatic channels identified lymphatic tumor emboli peripheral to and within the carcinomas, and distinguished bona fide intramammary lymphatic invasion from tissue shrinkage artefacts. The applicability to routinely processed tissue permits retrospective studies and renders the identification of intramammary lymphatic invasion a more objective procedure. Further studies are needed to assess the role of this technique in evaluating the prognostic value of intramammary lymphatic invasion; the technique may be extended also to the study of other neoplasms.

An adrenocorticotropic hormone-producing pheochromocytoma: diagnostic and immunohistochemical studies.

A patient is described with Cushings syndrome owing to a pheochromocytoma that was producing adrenocorticotropic hormone. Preoperative diagnosis was suggested by finding bilateral adrenocortical hyperplasia plus a separate unilateral adrenal medullary mass and was confirmed laboratory studies. Proper preoperative preparation was followed by a unilateral adrenalectomy and a clinical cure of both conditions. Immunohistochemical studies confirmed the ectopic production of adrenocorticotropic hormone and its related peptides more thoroughly than previous reports. The hormone production appeared clinically and immunocytochemically to resemble pituitary Cushings disease more closely than ectopic production of adrenocorticotropic hormone by other tumors. The clinical aspects of this case illustrate the importance of proper preoperative recognition to reduce the high known percentage of morbidity and mortality.

Splenic hamartoma with bizarre stromal cells

Splenic hamartoma is a rare entity characterized by disorganized red pulp tissue in the absence of interspersed white pulp. We report 3 cases with scattered bizarre stromal cells, a feature not previously reported in the literature. The patients were adults who presented with abdominal pain (2 cases) or were incidentally found to have a splenic mass (1 case). The lesion was solitary, circumscribed, and unencapsulated, comprising disorganized slit-like, tubular, ectatic or cavernous vascular channels. There was a loose stroma that contained lymphocytes, plasma cells, siderophages, and fibrin exudate. Scattered haphazardly were isolated bizarre large cells with oval, convoluted, or multilobated nuclei; pale or smudged chromatin; and scanty cytoplasm. Mitotic figures were not found. The bizarre cells were negative for lymphoid, dendritic cell, histiocytic, myeloid, endothelial, epithelial, and melanocytic markers. Only rare bizarre cells stained for desmin in 1 case. It is important to recognize this morphologic variant of splenic hamartoma in order not to misinterpret the bizarre cells as being indicative of a malignancy.