Cytologic "differentiation" in childhood rhabdomyosarcomas following polychemotherapy

The effectiveness of polychemotherapy in young patients with rhabdomyosarcomas has been well established. The morphologic alterations in the tumor tissue, however, have not been widely reported. Therefore, in a group of 15 patients from 1 to 24 years of age, specimens of tumor tissue obtained before and after polychemotherapeutic treatment were compared. No morphologic changes, other than fibrosis and necrosis, occurred in patients who initially had virtually undifferentiated tumors. When moderately or well-differentiated areas were present in the initial specimens, these areas showed proportionate increases in the follow-up specimens. Moreover, the cellular characteristics of round rhabdomyoblasts and strap cells with or without cross-striations became more distinct after treatment. However, cell types that were not present in the initial specimens were never found in follow-up specimens. It was concluded that the major role of polychemotherapy is the selective destruction of undifferentiated tumor cells; further differentiated cells are stimulated either directly or indirectly to reach their maximal inherent differentiation levels, but it does not appear that transitions from one cell type to the other occur.     

The ultrastructure of small cell lung carcinoma in bronchial biopsy specimens

Forty-three bronchial biopsy specimens from patients with small cell lung cancer (SCLC) were studied by electron microscopy. In 38 specimens the diagnosis was based on the light microscopic examination of Epon-embedded tissue; 36 of these specimens contained dense-core granules on electron microscopic examination. In five cases the light microscopic diagnosis was either different from the electron microscopic diagnosis or in doubt. Electron microscopy revealed dense-core granules as the only sign of differentiation, and the diagnosis was changed to SCLC. The tumor cell populations in the biopsy specimens were quite heterogeneous. Cells of the oat cell type were always present and, on electron microscopic examination, always showed degenerative changes. It was therefore decided that this cell type represents an artifact. The true SCLC tumor cell, which constitutes only a small portion of the tumor in biopsy specimens, is characterized by a regular oval or rounded cell with pale cytoplasm and a ground-glass nucleus with finely dispersed chromatin. Nucleolated cells, similar to those seen in large cell cancer, are often present but are not ultrastructurally different from nonnucleolated tumor cells.     

The primary immune response in bronchial asthma. I. A kinetic study of Helix pomatia hemocyanin-specific IgE, IgG, IgA, and IgM antibody responses in patients with asthma and in matched controls

Eleven asthmatic patients with allergy and 10 age- and sex-matched controls were immunized subcutaneously with 1 mg of the primary test immunogen Helix pomatia hemocyanin (HPH). The HPH-specific IgE, IgG, IgA, and IgM antibody response was measured by ELISA. After immunization, not only the IgE but also the IgG antibody response of the patients exceeded that of the controls (p less than 0.01). IgA antibody response also tended to be higher in the asthmatic group (NS). Except for an earlier rise after immunization in the asthmatic group (p less than 0.05), IgM peak responses did not differ significantly between the two groups. There was a high correlation (r = 0.9) between the magnitude of the IgE and the IgG antibody responses. IgM antibody response did not correlate with the response in any of the other antibody classes measured. The total serum immunoglobulin concentration was determined before immunization. Only the IgE level was significantly higher in the asthmatic group (p less than 0.01). No correlation was found between serum immunoglobulin concentrations and the magnitude of the HPH-specific antibody response in the same class. We conclude that the increased humoral responsiveness of asthmatic patients with allergy is not restricted to the IgE class nor to a limited number of commonly encountered antigens (allergens).     

Creatine kinase subunits M and B as markers in the diagnosis of poorly differentiated rhabdomyosarcomas in children

Antibodies against the M and B subunits of creatine kinase were assessed for their usefulness in the diagnosis of poorly differentiated rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin-biotin-peroxidase complex technique were used. The majority of the poorly differentiated and all of the moderately and well-differentiated rhabdomyosarcomas studied showed immunostaining for the M subunit. The rhabdomyoblastic component of malignant "triton" tumors was also positive. Staining, although weak compared with that of the rhabdomyosarcomas, was also observed in a few leiomyosarcomas, hemangioendotheliosarcomas, malignant fibrous histiocytomas, and ganglioneuroblastomas. On the other hand, staining for the B subunit was seen in many types of soft tissue tumors, including rhabdomyosarcoma, Ewing's sarcoma, and (ganglio)neuroblastoma. The results indicate that creatine kinase subunit M is a useful marker for distinguishing poorly differentiated rhabdomyosarcoma from other types of small round cell tumors in children, such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma.     

Intermediate filaments in Merkel cell tumors

A series of ten Merkel cell tumors is described, with special emphasis on intermediate filament expression. The presence of cytoskeletal proteins was studied with a polyclonal antiserum directed against cytokeratin and with monoclonal antibodies against cytokeratin, neurofilament, and vimentin by the immunoperoxidase technique. Cytokeratin was demonstrated in nine of ten tumors. Neurofilament was observed in the two snap-frozen tissues tested and in three of the eight formalin-fixed, paraffin-embedded tissues. No reactivity for vimentin was found. By electron microscopy desmosomes were found to be present in all cases, while tonofilaments were found in only a few cases. neurosecretory granules, although seen in all tumors, were generally present in low numbers. The results of this study indicate that the Merkel cell tumor is a poorly differentiated small cell carcinoma that has the ability to express some neuroendocrine features.     

A case of congenital esophageal stenosis

A case study of congenital esophageal stenosis is reported. Light microscopic examination revealed extensive disorganization of the inner circular muscle layer, with partial absence of the muscularis mucosae.     

An immunohistologic study of the epithelial and lymphoid components of six thymomas

Six thymomas were classified histologically and studied immunohistochemically with a panel of mouse and rat monoclonal antibodies directed against thymic epithelial and lymphoid components. The antibodies included monoclonal antibodies directed against cytokeratin, medullary epithelial cells (ER-TR5), and HLA-DR and HLA-ABC antigens, as well as antibodies with specificity for thymocytes. Histologically, one thymoma was characterized by epithelial predominance (EP type), two showed lymphoid predominance (LP type), and two showed mixed lymphoid/epithelial composition (MLE type); one thymoma was a malignant pure epithelial thymoma (PE type). In the thymomas of the MLE and EP types the major populations of cells consisted of HLA-DR-negative, cytokeratin-positive epithelial cells with large ER-TR5-positive subpopulations (i.e., the phenotype of medullary epithelium). In the thymomas of the LP type, the neoplastic population was composed of cytokeratin-positive, ER-TR5-negative cells that expressed the HLA-DR antigen (i.e., the phenotype of cortical epithelium). The thymoma of the PE type consisted of cytokeratin-positive cells, some of which were ER-TR5- and HLA-DR-positive. Double immunofluorescence studies revealed the presence of varying numbers of additional nonepithelial (nonlymphoid) HLA-DR-positive cells in thymomas of the LP, MLE, and EP types. The intervening lymphoid population in the thymomas of the LP, MLE, and EP types consisted largely of cortical thymocytes, as defined by immunologic characterization. These results suggest that thymomas can be classified as medullary or cortical epithelial neoplasms on the basis of their immunologic phenotypes.     

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.     

Primary malignant melanomas of the lung and adrenal

Malignant melanoma originating outside the skin, juxtacutaneous mucous membranes, eyes, and leptomeninges is a very rare neoplasm. Two such primary visceral malignant melanomas from the lung and adrenal are described in detail.     

Granulomatous prostatitis: distinction among allergic, nonspecific, and post-transurethral resection lesions

A variety of granulomatous lesions of the prostate, with and without extensive infiltration by eosinophils, have been described. Differing concepts of their pathogenesis, and especially of their relation to allergic states, have produced confusion and controversy. In a review of 62 patients in whom granulomatous lesions in the prostate were diagnosed from 1950 to 1982 at The Johns Hopkins Hospital, the authors identified four major categories. In nine cases specific granulomatous prostatitis was caused by tuberculosis and had typical caseous foci. Nonspecific granulomatous prostatitis was present in 31 cases. These lesions were densely cellular, granulomatous reactions extending throughout entire lobules; three were also characterized by extensive infiltration by eosinophils. Post-transurethral resection granulomas were found in 13 patients who had recently undergone prostatic surgery. These granulomas closely resembled rheumatoid nodules, and four were surrounded by numerous eosinophils. In nine patients the causes of granulomatous prostatitis were varied: two patients had malacoplakia, one had sarcoid, and six had foreign body-type granulomatous. No cases of allergic granulomatous prostatitis were identified. Nonspecific and post-transurethral resection granulomatous prostatitis may both show abundant infiltration by eosinophils and appear histologically identical to the condition that has been described as allergic granulomatous prostatitis; however, in this series both occurred in the absence of asthma or other allergies. The distinction between the rare allergic granulomatous prostatitis, as a reflection of a more generalized allergic reaction, and both post-transurethral resection granulomas and nonspecific granulomatous prostatitis is important, given the differences in clinical outcome and treatment.     

Incidence of IgA-related nephritides in American Indians in New Mexico

The racial distribution of the findings in 664 renal biopsies was studied for the state of New Mexico. The incidence of IgA-related nephritides (Berger's disease and Henoch-Sch?nlein purpura) was significantly greater in American Indians than in Hispanics and Anglos; IgA-related nephritides were found in 38 per cent of renal biopsies in American Indians. The clinicopathologic presentations of IgA-related nephritides were similar in the three ethnic groups.     

Segmental subepithelial deposits in primary glomerulonephritis: scanning electron microscopic examination of acellular glomeruli

More accurate perception of the structural alterations in glomerular basement membrane (GBM) produced by subepithelial immune complex deposits is possible with a recently adapted technique that uses scanning electron microscopy of acellular material. With this procedure frozen tissue is treated sequentially by osmotic lysis, detergents, and DNase to solubilize both cellular components and immune complex deposits. Four patients with glomerulonephritis (acute postinfectious glomerulonephritis [one patient], segmental membranous glomerulonephritis [two patients], membranoproliferative glomerulonephritis, type III [one patient]) in whom segmental subepithelial deposits were found were studied by this technique; the resulting observations were correlated with the results of routine morphologic studies and a previous study of minimal change disease and diffuse membranous glomerulonephritis. Four types of structural alterations of the subepithelial GBM surface were observed. The differences in lesions observed in the various forms of glomerulonephritis are believed to be related to temporal, quantitative, and qualitative differences in immune complex-mediated glomerular injury.     

Pulmonary veno-occlusive disease: involvement of pulmonary arteries and review of the literature

Pulmonary vessels from 26 patients with pulmonary veno-occlusive disease were studied histologically and morphometrically. In addition to the well-known obstruction of veins and venules, pulmonary arteries were also narrowed or obliterated in approximately half of the patients. It is unlikely that the arterial intimal fibrosis, which was sometimes as severe as the fibrosis in the veins, was secondary to the venous obstruction; rather, like the venous alterations, it probably resulted from organization of thrombi. It is possible that primary damage to the vascular wall elicited thrombosis. Such an injury may also have caused the arterialization of the venous walls, a common finding that cannot always be explained by distal narrowing of larger veins. Although the etiology of pulmonary veno-occlusive disease is obscure, it seems increasingly likely that multiple noxious agents may induce this condition. In children no predilection for either sex has been observed, but in adults, men are affected twice as often as women.     

Solitary solid stromal gastrointestinal tumors in von Recklinghausen's disease with minimal smooth muscle differentiation

Neurofibromatosis (von Recklinghausen's disease) is occasionally associated with large, solid stromal tumors of the gastrointestinal tract. The authors examined by electron microscopy two such cases of cellular spindle cell neoplasms of the small bowel histologically that resembled leiomyomas, in an attempt to clarify the cell of origin of these lesions. Ultrastructurally, the tumor cells predominantly contained moderate to large numbers of intracellular filaments, small cell processes, discontinuous adherent dense basement-membrane-like material, and abundant intercellular collagen. Definite fusiform dense bodies or structures highly suggestive of them and pinocytotic vesicles were seen in rare cells of each lesion after viewing multiple blocks. While patients with neurofibromatosis are certainly at risk of developing gastrointestinal Schwann cell neoplasms, these two cases suggest that they are also at risk for developing poorly differentiated stromal tumors, resembling leiomyomas by light microscopy, which may show only characteristic cytoplasmic differentiation of smooth muscle cells after ultrastructural examination of many sections.     

Pregnancy-associated plasma protein A: a clinically significant predictor of early recurrence in stage II breast carcinoma

The primary tumors and metastases from 30 patients with stage II breast carcinoma treated with low- or standard-dose combination chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil) were studied by the immunoperoxidase technique for pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific beta-1-glycoprotein (SP-1), and placental protein five (PP-5). In addition to immunostaining, 25 traditional clinicopathologic features were assessed with respect to early (at less than two years) recurrence. Of the 11 patients with early recurrences, nine (82 per cent) were PAPP-A-positive, while 16 of the 19 patients without early recurrences (84 per cent) were PAPP-A-negative (P less than 0.0005). None of the other clinicopathologic features correlated with early recurrence. Immunostaining for PAPP-A is thus a clinically significant predictor of early recurrence in patients with stage II breast carcinoma.     

DNA hybridization in diagnostic pathology

DNA hybridization is becoming an important new adjunct to conventional methods for the diagnosis of infectious diseases, inherited conditions, and neoplasia. Applications of this technology require very small quantities of tissue or body fluids because the DNA probes used in the hybridization assays detect minute amounts of homologous DNA sequence in the test material. Under the proper conditions, these DNA probes are absolutely specific for the pathogen or gene being examined, and hybridization with them usually yields objective answers that require little interpretation. The relatively minor inconveniences currently associated with DNA hybridization are related to the use of radioactivity as a detection signal and the time and labor required to obtain diagnostic data. In the future, technical improvements currently being developed and the preparation of new probes for additional human and microbial genes are likely to create an increasingly larger role for DNA hybridization in diagnostic pathology.     

Pulmonary air cysts in cystic fibrosis: relation of pathologic features to radiologic findings and history of pneumothorax

One lung obtained from each of 21 consecutive autopsies in adolescents and young adults with cystic fibrosis was studied prospectively by macroscopic morphometry and light microscopy to determine the prevalence, morphology, and radiographic appearance of subpleural air cysts, which potentially contribute to spontaneous pneumothorax. In 15 lungs, 41 cysts of three anatomic types were identified: bronchiectatic cysts (23), interstitial cysts (13), and emphysematous bullae (5). All cysts were significantly more numerous in the upper lobe. Bronchiectatic cysts had the largest mean diameter, occupied from less than 1 per cent to 47.7 per cent of upper lobe volume in nine patients, and produced large multiloculated hyperlucencies on chest radiographs in five cases. All six lungs with prior pneumothorax contained at least one cyst, but no significant difference was found in the type or proportion of lung volume occupied by cysts between lungs with and without pneumothorax. Patients with large cysts had significantly lower chest radiograph scores, but there was no correlation between the proportion of lung volume occupied by cysts and patient age or duration of either symptomatic lung disease or colonization by bacteria. On chest radiographs only bronchiectatic cysts with conglomerate diameters of greater than 3 cm were visible. Smaller lesions could not be separated from ring shadows produced by bronchiectasis.