Induction of severe granulomatous experimental autoimmune thyroiditis in mice by effector cells activated in the presence of anti-interleukin 2 receptor antibody.

Spleen cells from CBA/J mice immunized with mouse thyroglobulin (MTg) and the adjuvant lipopolysaccharide induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice if they are first activated in vitro with MTg. EAT induced by cells cultured with MTg is generally moderate in severity and is characterized by a thyroid infiltration consisting primarily of mononuclear cells. Addition of the anti-interleukin 2 receptor (IL-2R) monoclonal antibodies (mAbs) M7/20, 3C7, or 7D4 to spleen cell cultures with MTg resulted in a cell population capable of inducing a more severe type of EAT characterized by extensive follicular destruction, granuloma formation, and the presence of multinucleated giant cells. Recipients of cells cultured with MTg and anti-IL-2R mAb also had higher anti-MTg autoantibody responses than recipients of cells cultured with MTg alone. Activation of cells capable of transferring severe granulomatous EAT and increased anti-MTg autoantibody responses required both MTg and M7/20 in culture and required addition of M7/20 within the first 8 h of the 72-h culture period. CD4+ T cells were required for the expression of both the severe granulomatous EAT lesions and the mononuclear cell infiltrates typically observed in murine EAT. The increased anti-MTg autoantibody responses in recipients of cells cultured with MTg and anti-IL-2R mAbs were not restricted to a particular immunoglobulin G (IgG) subclass and included antibody of the IgG1, IgG2A, and IgG2B subclasses. These results suggest that a subset of CD4+ T cells capable of inducing severe granulomatous EAT and increased anti-MTg autoantibody responses is preferentially activated when cells are cultured in the presence of anti-IL-2R mAb. Anti-IL-2R mAb may either prevent activation of cells that induce classical lymphocytic EAT or prevent activation of cells that normally function to downregulate EAT effector T cell activity.

Effects of anti-I-A and anti-I-E monoclonal antibodies on the induction and expression of experimental autoimmune thyroiditis in mice.

Susceptibility to experimental autoimmune thyroiditis (EAT) in mice is linked to the I-A subregion of the major histocompatibility complex (MHC). The present study was undertaken to assess the effectiveness of anti-I-Ak monoclonal antibody (MAb) 10-2.16 in preventing or arresting the development of EAT. Spleen cells from CBA/J or (CBA/J x Balb/c) F1 mice given 10-2.16 prior to sensitization with mouse thyroglobulin (MTg) and adjuvant could not transfer EAT to normal recipients, and cells from these mice did not proliferate in vitro to MTg. Donor CBA/J mice given 10-2.16 before immunization and recipients of cells from such mice produced little MTg-specific IgG1 or IgG2b antibody but did produce nearly as much IgG2a as controls. The effects of in vivo treatment with 10-2.16 appear to be due to elimination of Ia + cells rather than to modulation of Ia or induction of suppressor T cells. When 10-2.16 was added to in vitro cultures it also prevented the proliferation and activation of sensitized CBA/J or F1 effector cell precursors. Other mAb specific for MHC class II gene products, but not associated with disease susceptibility, expressed by CBA/J (I-Ek) or F1 (I-Ad) mice (14-4-4S or MK-D6 respectively), also prevented in vivo sensitization, but did not block in vitro activation. Anti-I-Ak was also effective in preventing EAT if multiple injections of mAb were given to recipients of sensitized EAT effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Leiomyoma of the breast.

Leiomyoma of the breast parenchyma proper is a rare neoplasm. This tumor occurs predominantly in late middle-aged women and can be clinically difficult to discern from carcinoma. Mammographically, the tumor lacks typical features of carcinoma, but this possibility cannot be absolutely excluded. Immunohistochemical, ultrastructural, and DNA characteristics are reported in a new case. Mammographic findings are reported for the first time. Immunoperoxidase findings with antibodies to muscle-specific actin, desmin, vimentin, S-100 protein, and cytokeratins, as well as the ultrastructural features, suggest a pure smooth muscle cell origin and not a myoepithelial cell origin.

Pulmonary talc granulomatosis in a cocaine sniffer.

The development of pulmonary granulomatosis following intravenous injection of medications intended for oral use has been well described previously. Talc is the most commonly implicated agent. We present a case of talc granulomatosis which developed in a patient following cocaine sniffing and suggest that this may be the cause of development of granulomata in drug addicts who deny any history of intravenous drug abuse.

Immunostaining of cardiac biopsy specimens in the diagnosis of acute vascular (humoral) rejection: a control study.

The diagnosis of acute vascular (humoral) rejection in heart transplant biopsies is classically based on immunofluorescent studies of frozen tissue that show vascular staining for immunoglobulin and complement. We have noted that some pathologists have used immunostaining of formalin-fixed, paraffin-embedded tissue in testing for vascular rejection. To determine the specificity of immunostaining of heart biopsy specimens in the diagnosis of vascular rejection, we studied tissue from 68 consecutive endomyocardial biopsies from 16 patients without clinical or histologic evidence of vascular rejection. In each case, routinely processed formalin-fixed, paraffin-embedded tissue was stained for immunoglobulin G and immunoglobulin M with an avidin-biotin immunoperoxidase technique. Frozen tissue from each case was also stained for immunoglobulin G, immunoglobulin M, C3, and Clq by immunofluorescence. Immunoperoxidase stains on formalin-fixed tissue showed vascular staining for immunoglobulin in 67 of 68 (99%) of the cases. Staining was ablated if the antibodies were absorbed with their appropriate immunoglobulin. Immunofluorescent studies on frozen tissue showed no vascular staining for immunoglobulin or complement. We conclude that immunoperoxidase studies of routinely processed, formalin-fixed, paraffin-embedded tissues are nonspecific in the diagnosis of heart acute vascular rejection. The positive staining in fixed tissues may be due to labeling of passive immunoglobulins that are "fixed" in the vessels during routine processing but are washed away in techniques using frozen tissue.

Distribution of BCA-225 in adenocarcinomas. An immunohistochemical study of 446 cases.

BCA-225 is a glycoprotein identified in human breast carcinoma cells that has been reported to show a restricted distribution in other human tissues. To further define the presence of BCA-225 in human carcinomas, the authors performed an immunohistochemical study, applying a commercially available monoclonal antibody to BCA-225 to formalin-fixed, paraffin-embedded sections of 446 adenocarcinomas from a variety of sites. BCA-225 expression was found to be common in adenocarcinomas of the breast (98%), kidney (94%), ovary (80%), and lung (74%) but was infrequent in adenocarcinomas of the gastrointestinal tract (10-16%). Adenocarcinomas of the prostate, bile ducts, thyroid, endometrium, endocervix, and pancreas showed an intermediate frequency of BCA-225 expression (36-68%). Although rare tumor cells in three hepatocellular carcinomas showed reactivity for BCA-225, staining of more than 10% of the tumor cells was not seen in any of the 23 hepatocellular carcinomas that were studied. The authors conclude that BCA-225 is expressed commonly in human adenocarcinomas and that it is not a breast-specific antigen. Antibodies to BCA-225 may have utility in helping one to exclude hepatocellular carcinoma in certain clinical settings.

Nonspecificity of colon-specific antigen in adenocarcinomas. An immunohistochemical study of 422 cases.

To determine the specificity of colon-specific antigen in adenocarcinomas, routinely prepared paraffin-embedded tissue from 422 cases of adenocarcinoma were studied using a commercially available monoclonal antibody to colon-specific antigen and a standard avidin-biotin immunohistochemical technique. Positive reactivity for colon-specific antigen was very common (80% to 100%) in adenocarcinomas of the colon, distal esophagus/stomach, ovary, endocervix, endometrium, lung, pancreas, prostate, and bile ducts. Positive reactions were infrequent in adenocarcinomas of the breast (16%) and in hepatocellular carcinomas (23%). No immunoreactivity was seen in adenocarcinomas of the thyroid or in renal cell carcinomas. It is concluded that colon-specific antigen is not a colon-specific marker in adenocarcinomas. However, it may be useful in ruling out adenocarcinomas of renal or thyroid origin in certain clinical settings.

Acute leukemia/lymphoma of plasmacytoid T-cell type.

Plasmacytic morphologic characteristics are usually associated with cells of B-lymphocyte origin. Recently, plasmacytoid T-cells have been described in reactive lymph nodes and a rare form of lymphoma characteristically associated with myeloproliferative disorders. This report documents a case of plasmacytoid T-cell malignancy that initially presented as an acute leukemia in an elderly man with a longstanding myelodysplastic syndrome. The tumor replaced bone marrow and involved lymph nodes. Despite aggressive therapy, he died quickly of his leukemia/lymphoma. This case illustrates the need for complete cellular analysis in the diagnosis of morphologically plasmacytic malignancies and raises additional questions about the relationship of this peculiar type of T-cell to the hematopoietic marrow.

Lack of specificity of monoclonal antibody B72.3 in distinguishing chronic pancreatitis from pancreatic adenocarcinoma.

Making the morphologic distinction between chronic pancreatitis and pancreatic adenocarcinoma is a diagnostic challenge in small biopsy specimens and fine-needle aspiration samples. It has been suggested that immunohistochemical evaluation for the tumor-associated glycoprotein-72 antigen recognized by the monoclonal antibody B72.3 may be helpful in this setting. Formalin-fixed, routinely processed, paraffin-embedded tissue from 29 known cases of chronic pancreatitis and 31 cases of pancreatic adenocarcinoma were evaluated for reactivity with monoclonal antibody B72.3 using a standard avidin-biotin complex technique. Positive staining was seen in 26 of 31 adenocarcinomas (84%) and in 6 of 29 cases (21%) of chronic pancreatitis. Although monoclonal antibody B72.3 is more commonly reactive with pancreatic adenocarcinoma than with chronic pancreatitis, too many cases of chronic pancreatitis are reactive with this antibody for it to be useful as a diagnostic adjunct.

Topical vital staining of human squamous cell carcinoma xenografts in nude mice.

We propose a method for visually enhancing residual cutaneous carcinoma in excision sites using topical stains. Utilizing nude mice, topical stains were applied to fresh wound beds containing partially resected human squamous cell carcinoma xenografts. Fifteen of 18 tumors were visually enhanced using topical 1% acridine orange and ultraviolet light, while none of the seven tumors stained with 0.25% dihematoporphyrin ether and ultraviolet light were enhanced. Of the stains tested, only acridine orange proved to visually enhance tumor tissue in a fresh wound bed. This study establishes the concept of direct wound staining as an aid in the excision of cutaneous cancers.

Squamous cell carcinoma of the uterine cervix subsequent to amebiasis.

We studied the development of a well-differentiated squamous cell carcinoma of the uterine cervix five years after cervical infection with Entamoeba histolytica by documenting the findings of specimens obtained by repeated biopsies in a 69-year-old woman. To our knowledge, this is the first report of a malignant neoplasm of the uterine cervix subsequent to amebiasis. Amebiasis superimposed on malignant neoplasms of the female genital tract has been reported before. We raise the question of a possible causal relationship between amebiasis and subsequent squamous cell carcinomas of the cervix.

Utility of BER-EP4 in the diagnosis of adenocarcinoma in effusions: an immunocytochemical study of 232 cases.

The usefulness of a new commercially available monoclonal antibody (MoAb) BER-EP4 was evaluated. This MoAb is directed against a cell surface glycoprotein reported to be present in most epithelial cells and epithelial tumors but not in mesothelial cells. Cell block sections from 103 adenocarcinomatous and 129 benign effusions were studied. Positive staining was seen in 85 of the 103 (83%) malignant effusions. Immunoreactivity was seen in 73-93% of adenocarcinomas from the ovary, gastrointestinal tract, lung, and breast. Mesothelial cells from 3 of the 129 (2%) benign effusions showed positive staining. It is concluded that immunocytochemical staining with MoAb BER-EP4 is a sensitive and specific aid in distinguishing reactive mesothelial cells from adenocarcinoma cells in body fluids.

Ischemic colitis associated with dextroamphetamine use.

Ischemic colitis can be caused by a variety of medications including a number of sympathomimetic agents. We report the case of a 47-year-old narcoleptic man who had abdominal pain and rectal bleeding. The clinical, radiographic, and histologic findings supported the diagnosis of ischemic colitis associated with oral dextroamphetamine use.

Binding of soybean agglutinin lectin to prostatic hyperplasia and adenocarcinoma.

The binding of soybean agglutinin (SBA) lectin to routinely processed surgical pathology material from cases of prostatic hyperplasia, atypical hyperplasia, and adenocarcinoma was studied using an immunoperoxidase technique. Positive staining was obtained in eight of eight cases of nodular hyperplasia, eight of eight cases of atypical hyperplasia, and ten of 11 cases of adenocarcinoma. This report indicates that this lectin is not useful in distinguishing prostatic hyperplasia from adenocarcinoma.

Mediastinal histoplasmosis presenting with esophageal involvement and dysphagia: case study.

Esophageal involvement with histoplasmosis is uncommon, but has been recognized in two clinical settings. Most commonly, the esophagus becomes involved as a result of contiguous mediastinal lymphadenopathy. Such patients usually present with dysphagia secondary to midesophageal compression or stricture. The esophagus can also be involved in cases of disseminated histoplasmosis. Esophageal ulcers or nodular lesions are the usual clinical manifestations in this setting. We report a case of mediastinal histoplasmosis with esophageal narrowing and mucosal ulceration that presented with dysphagia. The diagnosis was established at thoracotomy by the histologic finding of necrotizing granulomas and a positive fungal stain. The case was successfully treated with amphotericin B. The literature on esophageal and gastrointestinal histoplasmosis is reviewed.

Immunohistochemical localization of granulocyte-macrophage colony-stimulating factor in matched endometriosis and endometrial tissues.

OBJECTIVE: Murine endometrial granulocyte-macrophage colony-stimulating factor has been related to macrophage recruitment and activation and postulated to mediate reproductive events. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor is present in normal human endometrium or endometriosis. STUDY DESIGN: Granulocyte-macrophage colony-stimulating factor was immunohistochemically evaluated in matched endometrial and endometriosis biopsy specimens (n = 19) and endometrial biopsy specimens from disease-free patients (n = 8). Staining differences were determined with McNemar's, Fisher's, and Wilcoxon's tests. RESULTS: Granulocyte-macrophage colony-stimulating factor was primarily localized in endometrial and endometriotic epithelial cells. Expression (p = 0.71) and staining intensity (p = 0.37) was similar in matched proliferative-phase endometrium and endometriosis. Matched secretory-phase endometrium and endometriosis also expressed granulocyte-macrophage colony-stimulating factor in similar proportions (p = 0.12), but staining intensity was enhanced in secretory endometriosis compared with secretory endometrium (p = 0.05). Endometrial granulocyte-macrophage colony-stimulating factor did not vary throughout the menstrual cycle, but endometriotic expression (p = 0.013) and staining intensity (p = 0.008) were significantly greater in the secretory phase. CONCLUSIONS: Granulocyte-macrophage colony-stimulating factor is localized in endometrial and endometriotic epithelial cells with increased expression in secretory-phase endometriosis. Granulocyte-macrophage colony-stimulating factor may elicit migration, proliferation, and activation of endometrial and peritoneal macrophages.

Induction of granulomatous experimental autoimmune thyroiditis in mice with in vitro activated effector T cells and anti-IFN-gamma antibody.

Experimental autoimmune thyroiditis (EAT) can be induced in mice after the transfer of mouse thyroglobulin (MTg)-sensitized donor spleen cells that have been activated in vitro with MTg. CD4+ T cells are required for the transfer of EAT in this model. Because CD4+ T cells produce various lymphokines, such as IFN-gamma, that may be involved in the activation or regulation of the immune response to MTg and the development of EAT, the present study was undertaken to determine whether a neutralizing mAb to IFN-gamma could modulate the induction or expression of EAT. The anti-IFN-gamma mAb XMG-1.2 had no effect on sensitization of donor cells. However, addition of XMG-1.2 mAb during in vitro activation of MTg-primed spleen cells resulted in more severe EAT in recipient mice. The thyroid lesions in recipients of cells cultured with MTg and XMG-1.2 mAb also exhibited granulomatous changes, which differed qualitatively from the predominantly lymphocytic cell infiltrates in recipients of cells cultured with MTg alone. Recipients of MTg-activated spleen cells also developed severe granulomatous EAT when they were given injections of XMG-1.2 mAb. The effects of XMG-1.2 could be neutralized by IFN-gamma. Recipients of cells cultured in the presence of XMG-1.2 mAb had augmented autoantibody responses, although there were no apparent differences in the IgG subclass distribution of the anti-MTg autoantibody responses. These studies suggest that neutralization of endogenous IFN-gamma results in increased activity of cells capable of inducing granulomatous EAT in mice.

Epidural spinal cord compression as the presenting manifestation of tumor of unknown origin.

Epidural spinal cord compression is a common complication of malignancy. In the majority of cases, the primary site is known at diagnosis or is evident following limited investigation. During the period January 1975 to December 1987 we encountered seven cases of tumor of unknown origin presenting as cord compression. Myelography detected the site of cord involvement in six cases, and computed tomography of the spine was utilized in one case. All seven patients underwent laminectomy. Histologic diagnosis was adenocarcinoma in four cases, squamous in one case, and large cell undifferentiated carcinoma in two cases. Evaluation for a primary site was unrewarding. Prognosis was poor, with a median survival of 10 weeks. Only one patient had a satisfactory response to treatment.