Isao Katayama

SUBACUTE NECROTISING LYMPHADENITIS:A Clinicopathologic Study

This report describes the clinical and pathologic findings of 21 patients with subacute necrotizing lymphadenitis (N.L.). Clinical features of all but 2 patients were as typically described in the literature; young age, enlargement of cervical or axillary lymph nodes, slight to moderate fever with poor response to antibiotics, and invariable spontaneous resolution. Two patients showed atypical clinical findings; remittent high fever with profound prostration in both patients, generalized lymphadenopathy in one, and being a Caucasian in the other. Systemic symptoms resolved gradually, and both patients are now doing well. One patient, however, underwent a staging laparotomy due to a misdiagnosis as unclassiflable lymphoma of the lymph node biopsy. Biopsies of the lymph nodes from all patients demonstrated the typical pathologic features of NL.; i.e., an intensive proliferation of activated lymphocytes mottled by necrotic foci in which polymorphonuclear leukocytes were characteristically absent. Bacteriologic and serologic studies were negative. We conclude that some patients with N.L. run a protracted course with remittent high fever before spontaneous resolution and that a correct pathologic diagnosis helps precluding unnecessary diagnostic or therapeutic measures on such patients.

PAP immunoperoxidase method demonstrating endogenous estrogen in breast carcinomas

A PAP immunoperoxidase method for demonstrating estrogen receptors in breast carcinomas is introduced. Whereas other methods pretreat the specimen with exogenous estrogen in high (unphysiologic) doses, this method demonstrates endogenous estrogen without such pretreatment. Experiments showed endogenous estrogen remaining in the formalin‐fixed, paraffin‐embedded breast tumors in sufficient amounts to be detected by the PAP method. The method can discriminate hormone responsive cells from hormone secreting cells because most responsive cells demonstrate both the cytoplasmic and nuclear stain and most secreting cells only the cytoplasmic stain. The method was applied to 277 human breast carcinomas, of which 197 (71.1%) were positive and 80 (28.9%) negative. These figures were comparable to those obtained by the biochemical methods. This PAP method may serve as an alternative to the biochemical assays of estrogen receptors.

Surface Phenotype and Adhesion Activity of B-Cell Chronic Lymphoid Leukemias

Surface phenotypes and adhesion activity to human umbilical vein endothelial cells (HUVECs) were studied using leukemic cells from 12 Japanese patients with B-cell chronic lymphoid leukemias including 7 with chronic lymphocytic leukemia (CLL), 1 with prolymphocytic leukemia (PLL), 2 with hairy cell leukemia (HCL) and 2 with HCL variant (HCL-V). CD13 and CD23 were found to be characteristically positive in CLL, whereas they were not expressed in non-CLL cases except for positivity of CD23 in two such cases. Except for CD11b, all other leukocyte integrins examined (CD11a, CD11c and CD18) and their ligand (CD54) were highly expressed in non-CLL cases. Adhesion activity of leukemic cells to HUVECs after co-culture with HUVECs was well correlated with the expression of CD11b, CD18 and CD54, but showed no predilection for any leukemia subtype. Positivity for CD5, CD21, CD23 and CD13 changed after the co-culture with HUVEC. These results suggest that adhesion activity after co-culture. does not correlate with the leukemia subtype and that endothelial cells activate or differentiate leukemic cells.

Congenital Neuroblastoma Presenting as a Paratesticular Tumor

A 1-month-old male newborn was operated upon for a scrotal tumor that was localized outside of the testis. Histological diagnosis was neuroblastoma. Although neuroblastoma often may present as metastatic disease when first seen, this case is unique in that an undetected adrenal neuroblastoma presented as a paratesticular tumor immediately after birth.

Role of apoptosis in spontaneous regression of peripheral T-cell lymphoma arising in the skin or subcutis

Apoptosis was suspected to play a significant role in spontaneous regression of skin lesions in four cases of peripheral T-cell lymphoma arising in the skin or subcutis. All of the patients had skin tumors with ulcer formation, but no metastasis to the lymph nodes or viscera. Biopsy showed a sea of CD3-positive lymphoma cells involving the dermis to the subcutis with scattered foci of coagulative necrosis. In the zone of incipient necrosis surrounding the core of coagulative necrosis, frequent apoptotic bodies were identified by electron microscopy (EM), and DNA strand breaks were detected in 34% to 51% (mean, 42%) of lymphoma cells by the TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL). As for the pathogenesis of coagulative necrosis, ischemic necrosis attributable to lymphocytic vasculitis appeared unlikely, because necrotic foci were devoid of neutrophils and had no relation to vascular distribution. Primary cataclysmic apoptosis appeared more likely, but its pathogenetic role could not be established, because EM and TUNEL could not be applied to the core of the debris-ridden coagulative necrosis. Although these cases had been classified as pseudolymphomas because they were histologically malignant but clinically benign, they were in fact true lymphomas characterized by extensive coagulative necrosis with a high rate of apoptosis demonstrable in the zone of incipient necrosis.

Interleukin 1 (IL-1α and IL-1β) induces differentiation/activation of B cell chronic lymphoid leukemia cells

The effect of interleukin 1 (IL-1) was studied on leukemic cells from 12 patients with B cell chronic lymphoid leukemias including two cases of hairy cell leukemia (HCL), two cases of HCL-variant (HCL-V), one case of prolymphocytic leukemia (PLL), and seven cases of chronic lymphocytic leukemia (CLL). In most cases, IL-1 induced differentiation characterized by increments of sIgγ+, sIgμ+ and PCA-1+ cells, and a decrement of CD5+ cells, and activation characterized by increments of CD23+ and HC2+ cells, but induced the proliferation of leukemic cells only in two HCL-V cases. Among these effects, increment of sIg+ cells was observed more frequently in non-CLL (45 cases) than in CLL (27 cases), and increments of sIgγ+, CD23+ and PCA-1+ cells were induced more frequently by IL-1β than by IL-1α. These results suggest that IL-1, especially IL-1β, plays a significant role in the differentiation and activation of leukemic cells, but has only a minor role as an extrinsic/autocrine growth factor. IL-1 may be useful for studying the differentiation pathway of leukemic cells in B cell chronic lymphoid leukemias, particularly those with more mature cells such as PLL and HCL.

Enzyme Histochemistry on Paraffin Embedded Tissue Sections

To obtain diagnostic enzyme reactions in paraffin embedded tissue sections, we compared four fixatives (buffered formol sucrose, Bakers formol calcium, periodate lysin paraformaldehyde, and buffered formalin acetone) and subsequent acetone dehydration with or without graded concentrations of Triton X-100. Four spleens and 14 lymph nodes were tested for peroxidase, naphthol ASD chloroacetate esterase, acid phosphatase, alpha naphthyl acetate esterase, and alpha naphthyl butyrate. Best results were obtained by a processing method using buffered formalin acetone, Holts gum sucrose, dehydration in acetone with 0.03% Triton X-100, and paraffin for embedding.

NAPHTHOL AS–D CHLOROAGETATE ESTERASE REACTION

Currently used methods for naphthol AS–D chloroacetate (NASDGA) esterase reactions can be divided Into 3 groups according to the coupler used, i.e., fast garnet GBC, pararosanllln, and new fuchsln. These 3 groups were systematically modified with regard to modes of fixation and Incubation in ordet to develop optimal methods for their application on sections of formalin–fixed and paraffin–embedded tissue as well as blood smears. After obtaining the optimal modifications for each of the 3 coupler methods, comparison was made between the 3 optimal methods for blood smears and the 3 for tissue sections. For blood smears, the methods using either fast garnet GBC or new fuchsin as coupler were found to be equally excellent, while the method using pararosanllln as coupler was not as superior. For tissue sections, the methods using either fast garnet GBC or pararosanilin were found to be equally excellent, while the method using new fuchsin was not as superior. Thus, only the method using fast garnet GBC as coupler was found excellent for both purposes. It was also found that bone marrow biopsies routinely processed through formalin–fixation would yield excellent NASDCA esterase reaction provided Plank and Rychlos method instead of EDTA was employed for decalcification. ACTA PATHOL. JPN. 33: 381 – 393, 1983.

Histochemical demonstration of endogenous estrogen in breast carcinomas: biochemical and clinical correlation *

In a study of 277 patients with breast carcinomas, the PAP immunoperoxidase method for demonstrating endogenous estrogen was correlated with the sucrose density gradient (SDG) assay and with histologic and clinical features. The results from the PAP method and SDG assay agreed in 59 of 84 patients (82.1%) on whom both methods were performed. Histologically, the PAP method was positive in 7 of 7 patients with non-invasive carcinomas, in 164 of 233 patients (70.4%) with common invasive ductal carcinoma, and in 21 of 22 of those with special histological types of invasive carcinomas not including Pagets disease, medullary or apocrine carcinoma, where only 5 of 14 were positive. Clinically, 15 of 18 patients with positive endogenous estrogen showed a response to endocrine therapy as opposed to 1 of 9 patients with a negative endogenous estrogen. The mean survival was 31.2 and 15.6 months, respectively for patients with positive and negative endogenous estrogen. Remission for longer than 2 years was seen more often in patients with positive endogenous estrogen. These results suggest a clinical utility of the present PAP method which, therefore, deserves a further trial as an alternative to histochemical methods aiming at the estrogen receptors.

Demonstration of p35 in hairy cell leukemia of Japanese patients.

Using SDS polyacrylamide gel electrophoresis (SDS‐PAGE), several coworkers isolated a unique membrane protein that they named p35 from hairy cells of white patients with hairy cell leukemia. In the current study using a similar technique, p35 was identified in hairy cells from 2 of 4 Japanese patients with hairy cell leukemia. Further, p35 was immunoprecipitated from the leukemic membrane proteins of one of these two Japanese patients with an anti‐hairy cell serum prepared against hairy cells of a typical white patient. Because both Japanese and white patients share the unique membrane antigen, it is proposed that the Japanese have the same hairy cell leukemia as whites despite some differences in laboratory features.