Biomedical subjects
Publications and source records attributed to T M Grogan.
New immunochemical staining techniques reveal key topographic aspects of splenic immune function. Distinct compartmentalization of B and T cells and lymphocytic subtypes within the white and red pulp of the human spleen provide a morphologic basis for division of labor in the immune response.
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Nine patients with "undifferentiated" lymphoma (DUL) of Burkitt's (AMB, four cases) and non-Burkitt's (NB, five cases) types were studied. All specimens stained for a single immunoglobulin light chain indicating a monoclonal B-cell lymphoid proliferation. Striking methyl green pyronine and punctate Oil-Red O staining were demonstrated in both groups. Histologic and cytologic examination demonstrated a lymphoid proliferation with a high mitotic count, a "starry-sky" pattern, prominent cytoplasmic basophilia and vacuolation in both subtypes. The AMB cases showed a predominance of regular nuclei with 3-5 basophilic nucleoli, while the NB cases showed slightly greater nuclear variability with a greater proportion of nuclei containing 1-2 eosinophilic nucleoli. The AMB patients were all children (median, 12 age years) and those with NB were adults (median, age 54 years). The site of presentation in both groups was predominantly extranodal and abdominal. This report emphasizes the considerable immunologic, morphologic, cytochemical and clinical overlap present among the subtypes of "undifferentiated" lymphoma.
The pathologic findings at autopsy in 124 patients with an initial diagnosis of Hodgkin's disease (HD) were evaluated to assess the effects of treatment on the anatomic extent and histologic appearance of residual HD. Further, the effects of duration of disease, vascular invasion, and histologic subtype at diagnosis on sites of involvement were considered. The 124 autopsied cases came from a cohort of 345 patients admitted for treatment at the National Cancer Institute between 1953 and 1969, with followup extended to 1978. The pathologic review included extensive organ sampling; greater than 12,000 slides were reviewed. The study period spans 25 years, ranging from a period of palliative therapy (81 cases, pre-1965) to the modern curative treatment era (43 cases, 1965 or later). A distinct reduction in the extent of disease at autopsy was noted in the group treated with curative intent. Reduced involvement was the rule for most, but not all, organ sites, with the reduction greater for certain histologic types. Some organs had a comparable incidence of involvement with early and late deaths. Histologic assessment identified an atypical monomorphic form of residual HD (treatment-altered HD) in patients from both treatment eras but most consistently in the post-1965 group. Vascular invasion occurred in 43% of cases. The incidence of extranodal involvement was considerably higher in patients with vascular invasion, indicating that vascular spread is a factor in extranodal spread and in lethal cases of HD.
Cytochemical, ultrastructural, and terminal deoxynucleotidyl transferase determinations in three cases of acute lymphocytic leukemia with azurophilic granules and punctate alpha-naphthyl acetate esterase (ANAE), alpha-naphthyl butyrate esterase (ANBE), and acid phosphatase (AP) activities further described a cytochemical and morphologic variant of acute lymphocytic leukemia. The ANAE, ANBE, and AP activities appeared specially localized within cytoplasmic granules. Electron microscopy substantiated a prominence of membrane-bound dense-core cytoplasmic granules. The variegated appearance of these dense-core granules and the cytochemical profile suggest that the aberrant granules are lysosomal in nature. Both the prominent cytoplasmic granules and the older age distribution led to early misdiagnosis of myelocytic leukemia. The distinctive cytochemical/morphologic profile and the ease of misdiagnosis suggest an important morphologic variant of acute lymphocytic leukemia.
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Pure RBC aplasia developed in two renal transplant recipients who were receiving long-term azathioprine therapy. With substitution of cyclophosphamide therapy for azathioprine, erythroid hyperplasia and reticulocytosis developed at three weeks in one patient and at three months in the other. Selective erythroid toxic reaction is a potential problem that must be considered when anemia develops in patients receiving long-term azathioprine therapy.
Observations surrounding the clinical manifestations and pathological studies of a neonate who died at 9 weeks of age, indicate that distinctive cutaneous, histopathologic, and ultrastructural findings occur when graft-vs-host reaction (GVHR) complicates combined immune deficiency syndrome (CIDS). The prominence and specificity of the epidermal lesions, particularly a necrotic cell that occurs in association with satellite lymphocytes ("satellite cell necrosis" (SCN)), lead us to recommend that a cutaneous biopsy be performed to facilitate an early definitive diagnosis. Dermatologists can recognize GVHR at the bedside and establish the diagnosis with the pathological findings obtained from the skin biopsy.
A female infant with combined immune deficiency syndrome exhibited graft-versus-host reaction (GVHR) clinically during the nine weeks of her life. Pathologically, the first clue for GVHR was the lymphohistiocytic dermal and epidermal infiltrate with single cell necrobiosis seen on a skin biopsy specimen at 6 weeks of age. Two days before death, she received irradiated (3,500 rads) whole blood and plasma with specific antibodies against mother's lymphocytes, which was the first introduction of an allogenic hematopoietic substance. This suggests that the GVHR, which was confirmed at autopsy, occurred as the result of maternofetal cell transfer in utero or at time of delivery.
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To determine the feasibility of liver biopsy immunotyping to characterize hepatic lymphoid malignancies, we employed a panel of monoclonal antibodies on snap-frozen hepatic tissue from 18 patients. Six patients proved to have a histologic diagnosis of lymphoid malignancy. By using free avidin and biotin-blocking reagents to block endogenous biotin, followed by standard immunochemistry, immunotyping was successful in all six cases. Serial section typing allowed delineation of complex B cell phenotypes. Furthermore, architecture was preserved allowing discernment of disease patterns (e.g., sinusoidal, hairy cell leukemia vs. portal, follicular small-cleaved cell lymphoma. Unexpectedly, we found striking expression of common ALL antigen in normal bile canaliculi, which may prove of diagnostic or therapeutic relevance. This study establishes the utility of immunohistochemical techniques applied to hepatic biopsies as a valuable adjunct to histologic diagnosis as well as a tool in revealing the immunobiology of the liver.
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Disseminated histoplasmosis was diagnosed by a computed tomographic (CT) directed needle biopsy of an adrenal mass. A 53-year-old man presented with a nonproductive cough, bilateral flank discomfort, and constitutional symptoms. Physical exam revealed mild hepatomegaly and tenderness. Chest radiograph revealed two destructive bone lesions. An abdominal CT scan demonstrated bilateral adrenal masses. Needle biopsy of the left adrenal mass revealed histoplasmosis. A rib resection or exploratory laparotomy was avoided. He has been completely free of evidence of disease for 6 months following completion of antibiotic therapy.
The purpose of this clinicopathologic overview is to describe the types of lymphomas that present in the mediastinum. A comparison of the frequency of the different subtypes of lymphoma that are found in children and adults is provided. In general, immunohistochemistry and immunophenotyping studies are essential to the laboratory workup of neoplasms presenting in the mediastinum. An assessment of proliferative index in lymphoma is most helpful to determine tumor aggressiveness and patient prognosis. Electron microscopy is most helpful in the differential diagnosis of mediastinal neoplasms, where lymphomas may be distinguished from nonlymphomatous neoplasms using key ultrastructural features. The role of electron microscopy in the subclassification of lymphomas is mostly academic, with a few exceptions. The varied ultrastructural appearance of Hodgkin's cells and of different subtypes of non-Hodgkin's lymphoma is illustrated, using cases from our patient files. An ultrastructural study of lacunar cells in Hodgkin's disease provides evidence that the formation of lacunae may have a structural and/or physiologic basis. Mummified cells showing some of the features of a physiologic form of cell death, called apoptosis, are also described.
The cutaneous T-cell lymphomas (CTCLs) comprise a spectrum of non-Hodgkin lymphomas with a predilection for the skin. This heterogeneous group of CTCLs include the prototypic CTCL mycosis fungoides (MF) and the recently described Ki-1+ lymphomas. MF is notoriously difficult to diagnose in its early stages. The histologic appearance of early MF is indistinguishable from that of chronic dermatitis. The limitations of light microscopy in the diagnosis of the CTCLs have led to the development of other diagnostic laboratory techniques. The best approach to the diagnosis of the CTCLs is a multidisciplinary one and should include ultrastructural morphometry, immunophenotyping, immunogenotyping, and histologic evaluation whenever possible. It is the purpose of this overview to point out the strengths and weaknesses of each of these techniques and, together with clinical input, to provide a comprehensive and rational approach to patient care.