Siblings with Bohring-Opitz syndrome.

We describe a brother and sister with Bohring-Opitz syndrome and suggest that autosomal recessive inheritance may occur in this condition.

Extramedullary plasmacytoma. A form of marginal zone cell lymphoma?

Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are related neoplasms, but EMP is clearly a distinct entity. Moreover, there are histologic and clinical similarities between EMP and marginal zone B-cell lymphomas (MZLs) displaying extensive plasma cell differentiation, suggesting a possible histogenetic relationship. The histologic and clinical features of 5 EMPs with extensive plasma cell differentiation were histologically reviewed for features of MZL. The previously diagnosed MZLs, mucosa-associated lymphoid tissue (MALT) type, of 2 patients also were reviewed. All patients were women aged 48 to 79 years. The EMPs originated in the parotid gland, lymph nodes, dura, or small bowel. The initial tumors diagnosed as MALT-type MZL were located in the lung and small bowel. All patients were treated with resection, with or without irradiation therapy. One patient also received systemic chemotherapy. All patients are alive with no evidence of disease. All tumors contained large numbers of plasma cells, constituting between 55% and 90% of the lymphoid cells. Centrocyte-like cells and monocytoid B cells each represented 0% to 25% of the infiltrate. Lymphoepithelial lesions were observed in all of the tumors in sites where epithelium was present. Reactive follicles were found in all of the tumors. EMPs may represent MZLs that have undergone an extensive degree of plasmacytic differentiation.

Sequential testicular biopsies in childhood acute lymphocytic leukemia.

Between August 1978 and November 1981, 33 boys with acute lymphocytic leukemia (ALL) (26 non-T, 7 T-cell) younger than 16 years underwent bilateral wedge testicular biopsies at the time of initial diagnosis. Seven (4 non-T, 3 T-cell) demonstrated focal leukemic infiltrates. Rebiopsy after successful induction therapy without testicular irradiation showed eradication of leukemic infiltrates in five, persistent focal infiltrates in one, and a diffuse infiltrate in one. The two patients who had persistent leukemic involvement had a T-cell phenotype, and in one of them overt testicular disease developed 2 years later. All 33 patients were followed prospectively for a minimum of 3 years. Fifteen (14 non-T, 1 T-cell) remained in remission for 3 years and underwent another testicular biopsy before the cessation of therapy. Two patients, both non-T and both of whom were free of testicular involvement at diagnosis, showed testicular infiltrates at that time. Of the seven boys with positive specimens at diagnosis, only two remained disease-free for 3 years and showed no testicular involvement upon the completion of chemotherapy. In this study, microscopic testicular involvement by lymphoblasts occurred in 21% of newly diagnosed boys with ALL; this occurred only if the leukocyte count exceeded 25,000/microliter. These patients in general had a poor prognosis, probably reflecting the overall heavy tumor burden. However, it was not possible to predict accurately those patients who would have leukemic testicular infiltrates at the cessation of chemotherapy by performing biopsy of the testes at the time of initial diagnosis or after induction therapy.

Lipoblastomatosis: ultrastructure of two cases and relationship to human fetal white adipose tissue.

Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum of adipose cell differentiation from mature adipocytes to undifferentiated mesenchymal cells. The cells had various shapes and were loosely related to one another and to small blood vessels in a stroma containing sparse collagen and proteoglycan granules. Adipocytes and lipoblasts had a discrete basal lamina but this was absent in immature mesenchymal cells, which had prominent intermediate (10-nm) microfilaments and few or no lipid droplets. Neither case had foci resembling brown adipose tissue or hibernoma (large polygonal cells closely apposed to one another and to capillaries with densely packed pleomorphic mitochondria and focal undulating plasmalemmal invaginations). Both the ultrastructure of lipoblastomatosis and its characteristic loose lobular arrangement by light microscopy closely resemble human fetal "white" adipose tissue.

Giant lymph node hyperplasia with unusual clinicopathologic features.

This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathologic features, both studied with immunohistochemical techniques. In the first case, mesenteric GLNH was associated with amyloidosis and the nephrotic syndrome. In the second, GLNH developed in a patient with previously treated Hodgkin's disease. In both cases, the GLNH was of the plasma cell variant. The plasma cells of the first case contained both kappa and lambda light chains, while those in the second case contained only the lambda light chain. The presence or absence of monoclonality was not predictable from the morphology alone. Cases of GLNH with unusual clinicopathologic features are reviewed and the significance of immunohistochemical studies discussed.

Congenital posterior urethral valves: problems of management in countries with limited facilities.

There is scanty reference in the literature from the tropics, especially from Africa, to posterior urethral valves (PUV). The condition is not uncommon in Africans. Forty-five patients seen during a period of 10 years at the Ahmadu Bello University Hospital, Zaria, Nigeria have been analysed in order to discover any problems this abnormality may pose that are peculiar to the developing countries of the tropics. Two-thirds of the patients were under one year of age when first seen, one-third of them being under one month. About a quarter had no urological symptoms at presentation. Most of these were neonates and infants often critically ill due to sepsis and uraemia. These non-urological presentations caused delay in diagnosis and referral with detrimental effects on prognosis. However, the diagnosis could be made on clinical examination by demonstrating a palpable bladder and/or renal masses. Voiding cystourethrogram confirmed the diagnosis when carried out carefully, and required no specialized equipment. Most children were treated satisfactorily by perineal valve ablation, using simple inexpensive instruments. The death rate was high mainly due to delay in diagnosis and in starting appropriate treatment. It is suggested that amongst all who have care of children in the tropics, increased awareness of the varied clinical manifestations of PUV would improve prognosis.

Hibernoma: distinctive light and electron microscopic features and relationship to brown adipose tissue.

Four hibernomas and samples of developing human brown and white adipose tissue were observed. Distinctive features of hibernomas were 1) lobules of closely apposed large polygonal cells and capillaries; 2) three principal cell types (granular eosinophilic, multivacuolated, and univacuolated) varying in prominence from case to case; 3) investment of each tumor cell by basal lamina; 4) an inverse relationship between lipid droplet size and the number of mitochondria per unit of cytoplasm; 5) pleomorphic mitochondria with dense matrixes or large, round mitochondria with transverse lamellar cristae; 6) undulating plasmalemmal invaginations; 7) micropinocytotic vesicles; 8) periodic short plasmalemmal densities; and 9) a conspicuous lack of cytoplasmic membrane systems. The frequent association of micropinocytotic vesicles and undulating plasmalemmal invaginations in proximity to capillaries strongly suggests that the invaginations represent a localized cell membrane adaptation for efficient endocytosis. In human fetal brown adipose tissue, which is first recognizable in fetuses of 21 weeks' gestational age, the most characteristic cell was the polygonal multivacuolated cell. Univacuolated cells were present in brown adipose tissue of older fetuses, and in infants and adults entire lobules containing univacuolated cells coexisted with lobules of multivacuolated cells and granular eosinophilic cells. The ultrastructure of human brown adipose tissue resembled that of hibernomas and was similar to previously described features of this tissue in animals. Developing white adipose tissue differed from brown adipose tissue by its loose plexiform arrangement of capillaries and spindle-shaped cells in less circumscribed lobules and by the absence of polygonal multivacuolated cells. The authors did not identify centripetal lobular maturation in white adipose tissue, but peripheral growth "caps" were a common finding in maturing brown adipose tissue. They consider brown adipose tissue to be a special form of adipose tissue, the variable cytologic composition of which is reflected in the histologic spectrum of hibernomas.

Plasmacytoma arising in giant lymph node hyperplasia.

Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient with GLNH of the chest wall had part of the lymph node replaced by large nodules of infiltrating plasma cells, and a serum paraprotein of the IgG lambda type. A peroxidase-antiperoxidase immunocytochemical technic showed that the plasma cells within areas of typical appearing GLNH were polyclonal, whereas those making up the nodular infiltrates were monoclonal. The observation of a plasmacytoma arising in this lesion demonstrates the neoplastic potential of GLNH.

Benign hemangioendothelioma of the testis: case report with electron microscopic documentation and review of the literature.

Tumors of non-specialized gonadal mesenchyme have been reported only rarely. An intratesticular benign hemangioendothelioma from a 26-year-old man presented a diagnostic challenge due to the infrequency of well-defined vascular lumens. Electron microscopy was helpful in defining the vascular nature of the tumor. In spite of the cellularity of the neoplasm, there has been no recurrence or metastasis over a two and one-half year follow-up period. The histological features are compared with those of previously reported cases.

Pretreatment testicular biopsy in childhood acute lymphocytic leukaemia.

Between August, 1978, and March, 1981, 24 boys with acute lymphocytic leukaemia (ALL) (14 non-B-cell non-T-cell, 6 pre-B-cell, and 4 T-cell) underwent bilateral wedge testicular biopsy at initial diagnosis. All testes were of normal size. Histological analysis was performed independently by three pathologists, 4 (3 non-B non-T, and 1 pre-B) of 20 patients with non-T-cell ALL demonstrated testicular focal lymphoblastic involvement. Successful induction chemotherapy without concomitant testicular irradiation completely eradicated testicular infiltrates in all 4 patients. Only 1 of the 4 T-cell patients had pre-treatment testicular infiltrates. Unlike boys with non-B non-T leukaemia, attainment of bone-marrow remission in this patient was associated with persistent testicular disease. These preliminary data indicate that in patients with ALL of non-T-cell type, systemic induction chemotherapy eradicates the small testicular infiltrates of lymphoblasts. Prophylactic testicular irradiation in this group of patients does not seem to be warranted.

A large functioning parathyroid lipoadenoma found in the posterior mediastinum.

A patient who was evaluated for a voice change was found to have a large posterior mediastinal mass on chest roentgenogram. Laboratory parameters suggested hyperparathyroidism. The 190-g resected tumor had the histologic features of a parathyroid lipoadenoma, that is, a diffuse mixture of parathyroid glandular elements and fat or myxoid stroma throughout. This case report emphasizes that the large size of these rare tumors may result in herniation into unusual sites, and this gives rise to a confusing clinical presentation. Ultrastructural analysis showed a uniform population of chief cells with a distribution of cellular organelles consistent with slow hormone production and release. Similarities to normal and adenomatous chief cells are discussed. The myxoid stroma surrounding the glandular elements had the ultrastructural features of loose connective tissue.

alpha-Naphthyl acetate esterase activity--a cytochemical marker for T lymphocytees. Correlation with immunologic studies of normal tissues, lymphocytic leukemias, non-Hodgkin's lymphomas, Hodgkin's disease, and other lymphoproliferative disorders.

Cytochemical identification of T lymphocytes on the basis of alpha-naphthyl acetate esterase (NAE) activity was compared with immunologic markers for cell suspensions and/or cryostat sections of 113 specimens. Nonneoplastic tissues (peripheral blood, lymph nodes, spleens, tonsils, thymus, and pleural fluid) and specimens from various lymphoproliferative disorders, including acute and chronic lymphocytic leukemia, lymphosarcoma cell leukemia, hairy cell leukemia, non-Hodgkin's lymphomas of B-and T-cell types, and Hodgkin's disease, were evaluated. T (E-rosetting) cells demonstrated several patterns of NAE reactivity: 1) a strong globular reaction product, the most specific pattern for T-cell identification, 2) granular cytoplasmic staining, or 3) no reactivity. B lymphocytes revealed a granular pattern of NAE staining, were devoid of enzyme, or, in rare instances, exhibited strong NAE activity. Percentages of lymphoid cells with strong (globular) NAE activity closely paralleled T-cell (E-rosette) values in the majority of cases, with the best correlations observed for peripheral blood studies. However, discordant results were noted for some neoplastic and nonneoplastic tissues, including cases of T-cell lymphoma or leukemia. Markedly discrepant results were noted for thymic lymphocytes, most of which revealed E-rosette formation and weak or absent NAE activity. Lymph nodes involved by Hodgkin's disease demonstrated a heterogeneous pattern of staining in E-rosetting cells and in Reed-Sternberg variants. Cryostat section studies of reactive lymph nodes and nodular lymphomas demonstrated strong NAE staining in lymphoid cells of T-cell (interfollicular, internodular) areas, with little or no positivity in follicles or nodules (B-cell areas). NAE staining patterns further suggested that T cells comprise part of the follicular cuff and possibly represent a minor population of some neoplastic nodules. Although NAE determinations do not represent a consistently reliable alternative to immunologic methods for T-cell identification, this easily applicable cytochemical marker is complementary to other techniques in assessing neoplastic or nonneoplastic tissues, particularly cryostat sections. (Am J Pathol 97:17--42, 1979).

Non-Hodgkin's lymphomas: an ultrastructural study correlating morphology with immunologic cell type.

Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type (NHL). Most B-cell lymphomas were comprised of neoplastic cells with morphologic features compatible with a follicular center cell origin. Dendritic reticulum cells and their desmosome-associated processes, characteristic of germinal centers, were observed in all 11 cases of nodular poorly differentiated lymphocytic lymphoma and in one of two cases of nodular "histiocytic" lymphoma, but were not identified in the lymphomas with a diffuse growth pattern. Desmosomes were observed between dendritic reticulum cells and were not found between lymphoid cells. Large neoplastic cells comprising lymphomas of "histiocytic," mixed lymphocytic "histiocytic," and "undifferentiated" types were characterized ultrastructurally and immunologically as lymphoid cells. Malignant lymphomas of well and moderately well differentiated lymphocytic types (7 cases) revealed B-cell markers, and represented a distinct homogenous group of neoplasms, with electron microscopic features most closely resembling follicular cuff lymphocytes. T-cell malignancies included lymphoblastic lymphomas (3 cases), large cell ("histiocytic") lymphomas (4 cases), lymphoepithelioid cell ("Lennert's") lymphomas (2 cases), mycosis fungoides (3 cases) and diffuse poorly differentiated lymphocytic lymphomas (2 cases). A consistent finding in the T-cell proliferations was the presence of small and/or large lymphoid cells with extremely irregular and/or convoluted nuclei, which occurred in varying proportions and with variable degrees of nuclear complexity. The nuclear irregularity evident in the neoplastic T cells was distinguishable from that observed for lymphoid cells of B-cell lymphomas. In comparing the cytoplasmic features of the T- and B-cell neoplasms ultrastructurally, the only distinguishing feature was the presence of well developed granular endoplasmic reticulum with dilated cisternae, i.e., plasmacytoid features, predictive of a B cell origin.

Giant hyperplastic parathyroid gland in the mediastinum--partially cystic and calcified.

A large, calcified paratracheal mass was identified in a patient with secondary hyperparathyroidism. The mass proved to be a giant, calcified, cystic, hyperplastic parathyroid gland. Radiographic and ultrasonic imaging techniques were quite useful in diagnostic evaluation. Whenever a calcified mediastinal or neck mass is discovered, especially in a patient with hyperparathyroidism, parathyroid enlargement should be a diagnostic consideration.