Biomedical subjects
E L Wiley
Publications and source records attributed to E L Wiley.
Pagetoid spread of intratubular germ cell neoplasia into rete testis: a morphologic and histochemical study of 100 orchiectomy specimens with invasive germ cell tumors.
Intratubular germ cell neoplasia (ITGCN) is now considered to be the preinvasive phase of testicular germ cell tumors with the exceptions of spermatocytic seminoma, pure yolk sac tumor, and mature teratoma. Pagetoid spread of ITGGN into rete testis is a common yet unpublished finding in these cases. We reviewed 100 cases of testicular germ cell tumors from the Surgical Pathology service of Parkland Memorial Hospital (Dallas, TX) to evaluate the frequency of this pattern of spread. Additional sections were obtained from selected cases and were stained with anti-placental alkaline phosphatase, anti-low molecular weight keratin (clone AE1), and various lectins to highlight the process. Pagetoid spread of ITGCN into rete testis was identified in 24 of 60 cases (40%) in which histologic sections contained both ITGCN and rete testis. The incidence of pagetoid ITGCN involvement of the rete testis was lower in pure seminoma (seven of 25 cases [28%]) than in testes containing nonseminomatous germ cell tumors (17 of 35 cases [49%]). AE1 stained the epithelial cells of the rete testis but not the cells of the ITGCN, whereas placental alkaline phosphatase stained the neoplastic cells but not the epithelial cells of the rete testis. These stains were useful in delineating two cases in which the pagetoid involvement was so extensive that they were misdiagnosed as invasive seminomas. Pagetoid spread of ITGCN is a relatively common finding in testicular germ cell tumors and rarely can be mistaken for invasive seminoma. Immunohistochemistry can be helpful in distinguishing florid pagetoid spread from invasive seminoma.
Expression and regulation of steroid 5 alpha-reductase 2 in prostate disease.
The androgen dihydrotestosterone is synthesized by the enzyme steroid 5 alpha-reductase, and it is required for growth and development of the prostate. We used immunohistochemistry to examine the expression of the type 2 isozyme of 5 alpha-reductase in benign prostatic hyperplasia and prostate cancer. The type 2 isozyme is highly expressed within stromal cells in both disease states. No type 2 isozyme is detectable in a lymph node metastasis. Immunoblotting studies show that androgen ablation therapies substantially decrease isozyme expression in the epididymis but have a lesser effect on expression in the prostate. Finasteride therapy (2 weeks to 3 years) did not abolish expression of the prostatic type 2 isozyme nor did this drug treatment induce expression of the type 1 isozyme.
Cell type specific expression of steroid 5 alpha-reductase 2.
Isozymes of steroid 5 alpha-reductase (5 alpha-reductase) have crucial roles in androgen physiology by synthesizing the potent hormone dihydrotestosterone. The expression pattern of the 5 alpha-reductase type 2 isozyme was determined in genital and extragenital tissues by developing an immunohistochemical assay using formalin-fixed tissue and affinity purified polyclonal antibodies that specifically recognize this isozyme. Expression was detected in basal epithelial and stromal cells of the normal prostate but not in luminal epithelial cells. Stromal cells of the seminal vesicle also expressed the type 2 isozyme. In contrast, staining was detected in epithelial cells of the epididymis but not in the surrounding stroma. Myofibroblasts in foreskin samples of normal and hypospadiac individuals expressed antigen and were distributed in bands throughout the prepuce, suggesting a clonal origin. In most cells the type 2 isozyme exhibited a perinuclear subcellular distribution. However, in liver hepatocytes the protein was distributed throughout the intracellular membrane compartment.
Primary leiomyosarcoma of the seminal vesicle.
A case of leiomyosarcoma of the seminal vesicle is described in a 68-year-old man. Digital rectal examination and pelvic computed tomography (CT) scan disclosed a large pelvic mass in the region of the prostate, whereas magnetic resonance imaging (MRI) suggested that the mass arose from the right seminal vesicle. Biopsy of the mass revealed a high-grade malignancy, thus a radical cystoprostatectomy was performed. Pathologic examination revealed a leiomyosarcoma arising from the right seminal vesicle. The patient is well and free of recurrent disease 13 months following surgery.
The tubular variant of adenoid cystic carcinoma of the Bartholin's gland.
The authors report two examples of the tubular variant of adenoid cystic carcinoma of the Bartholin's gland. Each occurred in young women (both aged 34 years) and presented with a painful indurated mass, clinically thought to be of inflammatory nature. On microscopic examination, the most distinctive feature was the haphazard proliferation of bland-appearing tubular structures often lined by two cell layers. A thin, periodic acid-Schiff-positive basement membrane immunoreactive for collagen IV surrounded the tubules, but hyaline globules were virtually absent. The inner cell layer was strongly and diffusely cytokeratin positive, whereas epithelial membrane antigen reactivity was seen only along the luminal borders. Focal positivity for S100 protein identified the peripheral myoepithelial cells, which were confirmed by electron microscopy. Focal perineural invasion was seen. The histologic, ultrastructural, and immunohistochemical features of these tumors are similar to those of the tubular variant of adenoid cystic carcinoma arising in major and minor salivary glands. In one of the cases, which was followed for 6 years, the tumor metastasized, despite the low histologic grade, and the patient died. Similarities and differences between the tubular, cribriform, and solid variants and other vulvar tumors are discussed.
Detection of Mycobacterium avium-intracellulare complex in bone marrow specimens of patients with acquired immunodeficiency syndrome.
Thirty-seven bone marrow core biopsy specimens from 21 human immunodeficiency virus-infected patients with Mycobacterium avium-intracellulare complex bacteremia were stained using rabbit polyclonal antibodies against Mycobacterium bovis strain Bacillus-Calmette-Guerin (BCG) and Mycobacterium duvalii, as well as Kenyon and Fite stains, to compare sensitivities of these techniques and evaluate possible response to therapy. The patients in this study had participated in a phase I/II trial of liposome-encapsulated gentamicin therapy. Two biopsy specimens had inadequate tissue for evaluation. Thirty-two specimens demonstrated bacilli with anti-M duvalii, 33 with anti-BCG, 20 with Kenyon, and 23 with Fite. Two were negative with all stains. Fifteen biopsy specimens had epithelioid granulomas, 12 had histiocytic granulomas, and 1 had a granuloma of indeterminate type. The remaining seven biopsy specimens had no granulomas. Four of these seven demonstrated bacilli with anti-M duvalii, 5 with anti-BCG, 1 with Kenyon, and 2 with Fite. The number of M avium-intracellulare organisms per milliliter of blood decreased in 14 of 21 patients after liposome-encapsulated gentamicin therapy. However, none of the 11 patients whose pre- and post-therapy bone marrow core biopsy specimens were both evaluable demonstrated a reduction in the number of M avium-intracellulare organisms. The authors concluded that anti-M duvalii and anti-BCG are more sensitive than acid-fast stains for identifying M avium-intracellulare infection in bone marrow core biopsy specimens of patients who have acquired immunodeficiency syndrome (AIDS) with M avium-intracellulare bacteremia. Bone marrow core biopsy specimens may provide a perspective on M avium-intracellulare infection in AIDS patients that differs from the one provided by blood cultures.
Opportunistic events and p17 expression in the bone marrow of human immunodeficiency virus-infected patients.
Bone marrow biopsies from 114 human immunodeficiency virus (HIV)-infected patients were stained with an anti-p17 monoclonal antibody to detect active HIV replication and associated factors. Immunoreactive p17 was found as virus-like particles in macrophages and dendritic cells and occasionally in megakaryocytes in 62 of 114 marrows and was considered evidence of active HIV replication. Immunoreactive p17 was not found significantly more often in the marrows of patients with lower CD4 cell counts; however, it was found significantly more in the marrows of patients with concurrent mycobacterial or fungal infections or lymphoma (chi 2 = 12.1, P < .001). Immunoreactive p17 was even more frequent when these opportunistic diseases were found in the biopsied marrow (chi 2 = 20.5, P < .001). The association of active HIV replication with certain opportunistic diseases, but not with lower CD4 cell counts, raises the possibility that these opportunistic diseases may under some circumstances be a cause as well as a consequence of active HIV replication.
Sweat gland adenomas: immunohistochemical study with emphasis on myoepithelial differentiation.
Thirty-one dermal appendage tumors of sweat gland differentiation including 7 spiradenomas (SPA), 8 cylindromas (CYL), 8 acrospiromas (ACS), and 8 chondroid syringomas (CS) were analyzed using antibodies to epithelial membrane antigen (EMA), cytokeratin (AE1, AE3, CAM 5.2, 34BE12), S-100 protein, actin (ACT), and desmin (DES) to characterize the immunocytochemical profile of benign sweat gland tumors. Cytokeratin expression was variable; AE1, 34BE12, AE3, and CAM 5.2 were present in 31, 24, 23, and 22 tumors respectively; 29 tumors contained EMA. Seventeen tumors, (6 SPA, 8 CYL, 2 ACS, 1 CS) stained with antibody to alpha smooth muscle actin, and 26 (7 SPA, 7 CYL, 4 ACS, 8 CS) expressed S-100 protein. Although some prior studies had reported actin filaments on electron microscopy in both spiradenoma and cylindroma, these tumors have previously been considered to be negative for myoepithelial differentiation. All spiradenomas and cylindromas we studied demonstrated actin and/or S-100 protein positivity in basal epithelial cells, consistent with myoepithelial differentiation. The organization of actin and S-100 protein positivity displayed by the spiradenomas and cylindromas we studied suggests that the tumors are differentiated towards the secretory portion of the eccrine sweat gland.
Fibrous histiocytoma of the parotid gland.
The light microscopic, electron microscopic, and immunocytochemical characteristics of a case of a fibrous histiocytoma arising in the parotid gland is presented. This neoplasm is very rare in this site and must be distinguished from other spindle cell tumors of the parotid gland, particularly those of epithelial and myoepithelial origins. Histologic characteristics similar to those displayed by dermatofibromas and dermatofibrosarcoma protuberans help to differentiate this tumor from other spindle cell tumors. The absence of cytochemical epithelial markers and the electron microscopic demonstration of fibroblasts and histiocytes are useful in establishing the diagnosis. This tumor, which was confined completely to the parotid gland, appears to have arisen from mesenchymal elements within the gland.
Monoclonal antibody to Pneumocystis carinii. Comparison with silver stain in bronchial lavage specimens.
Monoclonal 3F6 anti-Pneumocystis carinii antibody (MAB-3F6) was used to stain cell blocks from 164 bronchial lavage specimens from patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex and compared with slides stained with Grocott's modification of the Gomori methenamine silver stain. Pneumocystis organisms were present in 83 of 164 cases using MAB-3F6 stain, whereas Grocott's modified silver stain demonstrated Pneumocystis organisms in 48. MAB-3F6 demonstrated Pneumocystis organisms in 38 cases with negative silver stains, whereas silver stain identified Pneumocystis organisms in only three MAB-3F6-negative cases. Of 70 patients with clinical Pneumocystis pneumonia at the time of the specimen was obtained, 59 had MAB-3F6-positive specimens, whereas 39 had organisms detected using Grocott's modified silver stain. Of 37 patients without clinically apparent Pneumocystis pneumonia any time in their course, 4 had abundant organisms and 33 had negative stains with MAB-3F6. MAB-3F6 detected Pneumocystis organisms in 22 of 31 cases of Pneumocystis pneumonia that had no organisms identified using Grocott's silver stain (X2 = 5.76, P = 0.016). MAB-3F6 immunochemical staining is a more sensitive method than Grocott's modified silver stain to detect Pneumocystis organisms.
Adrenal carcinoma presenting as a lesion resembling cutaneous angiosarcoma.
A case is reported of adrenal carcinoma presenting as an angiosarcoma-like metastasis in the scalp. Adrenal carcinoma is a rare tumor, and it metastasizes to skin rarely. The authors discuss the features of this tumor that led to a diagnosis of angiosarcoma and the means by which such a metastasis may be distinguished from vascular tumors.
Reactivity of fungal organisms in tissue sections using anti-mycobacteria antibodies.
Sixty-four cases of deep fungal infections diagnosed using PAS or silver stains and 18 control cases of sarcoidosis, M. tuberculosis and M. leprae infection were stained using commercial polyclonal antibody raised against M. paratuberculosis (MP), M. Duvalii (MD), and Bacillus Calmette-Guerin (BCG). Nine of 13 cases of sporotrichosis stained positively using anti-MP antibody only; 13 of 14 cases of histoplasmosis stained with anti-BCG, anti-MD, and anti-MP; seven cases of cryptococcosis had only focal staining of rare individual organisms within masses of negative organisms; seven of eight cases of coccidioidomycosis stained predominantly with anti-BCG and anti-MP; eight cases of aspergillus had focal (1 to 5% of organisms) staining of hyphae with anti-BCG and anti-MD; and four of 12 cases of Candida infection showed focal nonspecific staining with both antibodies and nonimmune serum. Control cases of sarcoidosis exhibited no staining with any of the three antibodies, whereas cases of mycobacterial infection showed staining of bacilli and intracellular debris with all three antibodies.
Cutaneous phaeohyphomycosis caused by a rare fungal pathogen, Hormonema dematioides: successful treatment with ketoconazole.
Annular, fungating, ulcerated lesions developed on both hands of a 64-year-old immunocompetent man 2 months after he was cut with barbed wire. A dematiaceous mold, Hormonema dematioides, heretofore not definitively associated with human disease, was grown from two separate tissue specimens during a period of 9 days. Histopathologic examination demonstrated rare small, periodic acid-Schiff-positive, hyaline, yeastlike organisms in tissue. Twelve weeks of empiric therapy with ketoconazole, 400 mg/day, was curative.
Bilateral synchronous testis tumors of different histology in a patient with the acquired immunodeficiency syndrome related complex.
The incidence of bilateral testis tumors is approximately 1.5%. Of these cases the majority have the same histological status and few occur synchronously. Recently, an increased number of nonseminomatous germ cell tumors have been reported in the acquired immunodeficiency syndrome population. We describe a rare case of bilateral synchronous testis tumors of different histological status (seminoma and embryonal cell carcinoma) in a patient with the acquired immunodeficiency syndrome related complex. The patient was managed with bilateral orchiectomy and retroperitoneal lymph node dissection. Pathological stage was B1. The treatment was complicated by the fact that the patient is on azidothymidine, a drug that causes bone marrow suppression as a side effect. Because of persistent neutropenia no chemotherapy was given. The patient had no evidence of disease almost 1 year after retroperitoneal lymph node dissection.
Immunohistochemical demonstration of H antigen, peanut agglutinin receptor, and Saphora japonica receptor expression in infant thymuses and thymic neoplasias.
Ten infant thymuses and 13 primary thymic tumors obtained from archived paraffin-embedded tissue were examined for the presence of tissue blood group O antigen (H), peanut agglutinin receptor antigen (PNA-r), Saphora japonica agglutinin receptor antigen (SJA-r), carcinoembryonic antigen (CEA), cytokeratin (CK), and epithelial membrane antigen (EMA). In the thymuses studied, Hassall's corpuscles contained abundant immunoreactive CK, PNA-r, and H antigens, whereas CEA, SJA-r, and EMA were present focally in Hassall's corpuscles. Immunoreactive CK, PNA-r, and CEA were demonstrated focally in the subcapsular region, cortical nurse cells, and subcapsular-perivascular monocytic cells, respectively. PNA-r was present in all 12 epithelial type tumors, including all eight thymomas. CEA was present in nine tumors, including six thymomas. Six thymomas contained H antigen and SJA-r; five continued CK and EMA. SJA-r and EMA were also present in one carcinoid tumor of thymic origin. In epithelial thymomas, the antigens stained nests of epithelial cells resembling the pattern of staining in Hassall's corpuscles. Membrane staining of spindle cells of both spindle cell and epithelial thymomas was less intense than staining of epithelial type cells.
Polyclonal antibodies raised against Bacillus Calmette-Guerin, Mycobacterium duvalii, and Mycobacterium paratuberculosis used to detect mycobacteria in tissue with the use of immunohistochemical techniques.
Commercially available polyclonal antibodies raised against strains of mycobacteria were used to detect organisms in tissue sections from 34 cases of tuberculosis, leprosy, and atypical mycobacteria. Thirty-two cases of fungal infections, granulomatous inflammation, and sarcoidosis were used as negative controls. Sections stained with the use of antibodies raised against Bacillus Calmette-Guerin (BCG), Mycobacterium duvalii (MD), and Mycobacterium paratuberculosis (MP) were compared with Kinyoun and Fite-stained tissue sections. In caseating granulomata, clumps of mycobacterial debris, cells, and cell fragments stained. In histiocytic granulomata of mycobacterial infections, histiocyte cytoplasm contained both organisms and debris. The three antibodies showed cross-reactivity against the four groups of mycobacteria tested. Mycobacterial staining using immunoperoxidase was apparent in most cases at low-power (scanning) magnification. Thirty-two of 34 cases of mycobacterial infection, including all 24 Kinyoun-Fite-positive cases, were positive for immunoreactive organisms and debris using anti-MD, anti-BCG, and/or anti-MP. Eight of ten cases of culture-proven mycobacterial infection, in which Kinyoun and Fite stains were negative, had immunoreactive organisms or antigen with anti-BCG, MD, or MP. The antibodies also stained organisms in five cases of sporotrichosis in which the organisms were identified as yeast forms in tissue sections.
H, peanut lectin receptor, and carcinoembryonic antigen distribution in keratoacanthomas, squamous dysplasias, and carcinomas of skin.
The distribution of blood group antigen H(O), peanut lectin receptor (PNL-R) (a precursor to the MN blood group antigens), and carcinoembryonic antigen (CEA) was examined in 15 squamous cell carcinomas, 10 keratoacanthomas, 17 squamous dysplasias, and 5 normal controls using immunoperoxidase techniques. All controls and 8 carcinomas, 10 keratoacanthomas, 14 dysplasias expressed H antigen. All controls and 9 carcinomas, 10 keratoacanthomas, 16 dysplasias expressed PNL-R antigen. CEA was present in 15 carcinomas, in trace amounts in 3 keratoacanthomas, in 6 dysplasias, and in 0 controls. The staining for H antigen and PNL-R in the carcinomas and dysplasias was disorganized, patchy, and less than that of normal epithelium, while staining in keratoacanthomas was uniform, with normal to increased intensity as compared to controls in 9 cases. CEA showed weak focal staining in 5 carcinomas, 8 dysplasias and 3 keratoacanthomas, and more intense and extensive cytoplasmic and membrane staining in 10 carcinomas and 5 dysplasias, and no cellular staining in 4 dysplasias and 7 keratoacanthomas. CEA was present in greatest amounts in the well-differentiated carcinomas and focal in the less-differentiated tumors. The well-differentiated carcinomas had a greater percentage of cells staining for H antigen and PNL-R. The pattern of staining for H, PNL-R, and CEA appears to distinguish keratoacanthomas from carcinomas and squamous dysplasias, and may be a useful adjunct to diagnosis.