Thomas A. Seemayer

Infiltrating lipomas and angiolipomas revisited

Twenty‐seven soft tissue tumors composed of benign adipose tissue are presented featuring extensive local invasion and recurrence. Infiltrating angiolipomas and infiltrating lipomas are two distinct entities with different clinical and histologic features. The surgical approach demands wide local excision assisted by frozen section analysis to assure adequacy of removal. Extensive histologic sampling is mandatory to demonstrate the infiltrative character of the tumor and yet eliminate from consideration liposarcoma with which it may be confused. Although locally recurrent, neither has yet undergone malignant transformation.

The Functional and Histological Basis for Graft‐versus‐Host‐Induced Immunosuppression

The GvH reaction resulting from the injection of parental strain cells into adult F1 hybrids suppresses both cell-mediated and humoral immune responses and is dependent on the donor-host combination and the number of parental cells used to induce the GvH reaction. The early suppression is due, at least in part, to the increased number of macrophages and the activation of suppressor macrophages which act directly on the T-helper cell and perhaps the B-cell as well. The macrophage suppression is associated with an increase in PGE production. The long-term T-cell immunodeficiency is mediated by GvH-induced thymic dysplasia resulting in a block or an arrest in T-cell differentiation and deficient IL-2 production. The B-cell immunodeficiency is associated with both a decrease in B-cell production from lymphoid progenitors and a decrease in CFU-s production. The GvH reaction induces 2 types of thymic lesion, a stress-related effect causing atrophy of the thymic cortex and a cytolytic process causing severe-to-moderate lesions in the thymic medulla as a consequence of injury to medullary epithelial cells and a loss of Hassalls corpuscles (thymic dysplasia). By employing the NK-cell-deficient beige mutation, it was shown that the severe-to-moderate thymic medullary lesions occurred in F1 mice only in those transplant situations in which the donor inoculum was of the +/bg genotype, regardless of the genotype of the recipient. It is proposed that activation of parental T cells may contribute to the early immunosuppressive events; however, the relatively permanent immunosuppression appears to be associated with NK-like effector cells which are capable of causing injury to lymphoid and epithelial tissue, especially epithelium of the thymic medulla. These studies raise the possibility that the GvH reaction may contribute to some T- and B-cell immunodeficiencies observed in the SCID and AIDS syndromes, as well as in patients following bone marrow transplantation.

Peripheral nerve tumors involving paranasal sinuses: A case report and review of the literature

A 45‐year‐old man, afflicted with von Recklinghausens disease, with symptomatic schwannomas and plexiform neurofibromas involving the right maxillary antrum, a rare site for peripheral nerve tumors, is presented. After a literature review, 15 cases were considered adequate for a clinicopathologic study. Twelve schwannomas, 2 plexiform neurofibromas, 2 neurofibromas, and 1 probable malignant schwannoma were included. Epistaxis was common in tumors of the ethmoid sinus and nasal fossae, while pain was related to lesions of the maxillary sinus. Two benign schwannomas recurred and were cured by surgery alone. The importance of early diagnosis and thorough surgical excisions is emphasized, especially for those tumors associated with von Recklinghausens disease. The difficulties involved in the diagnosis of primary malignant peripheral nerve tumors are discussed.

Stromal myofibroblasts in primary invasive and metastatic carcinomas

A series of 23 primary invasive and 7 metastatic carcinomas was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunofluorescence (IF), the latter employing an anti-actin antibody. The results were correlated with macroscopic features such as retraction and consistency. Stromal cells rich in actin, readily identified by IF in firm and retracted carcinomas, were rare or absent in neoplasms lacking these features. TEM established the myofibroblastic nature of these stromal cells. Alternate sections (LM, IF) of each neoplasm demonstrated that myofibroblasts were more numerous in “young” mesenchymal stroma than in densely sclerotic areas. The connective tissue adjacent to intraductal mammary carcinoma lacked myofibroblasts, suggesting that epithelial stromal invasion is required to evoke a myofibroblastic stromal response. Myofibroblasts which possess synthetic (type III collagen) and contractile properties may well contribute to the firm consistency and retraction which characterize many carcinomas. The induction of myofibroblasts might represent an important host stromal response directed toward containment of invasive and/or metastatic carcinoma. This response may be especially important in neoplasms with weak antigenicity and/or slow doubling times.

Diabetes prevention in BB rats by inhibition of endogenous insulin secretion

Chronic prophylactic exogenous insulin treatment commenced in young diabetes susceptible BB rats has been shown to prevent type I diabetes. This study was undertaken to examine whether this diabetes protection resulted from inhibition of beta-cell insulin secretion by exogenous insulin administration or from either a metabolic (chronic hypoglycemia) or immune effect of this treatment. We compared the effects of prophylactic exogenous insulin treatment with those of an insulin secretion inhibitor, diazoxide, an oral hypoglycemic agent, glyburide, and, water alone as controls in randomly divided BB diabetes-prone littermates treated from age 30 to 150 days. These experiments confirmed that exogenous insulin can prevent type I diabetes in the BB rat. Diazoxide, which inhibits endogenous insulin secretion while causing hyperglycemia (rather than hypoglycemia with insulin), also offered protection from diabetes. In contrast, the oral hypoglycemic agent glyburide, which increased insulin secretion, but decreased plasma glucose during the early part of the experiment, did not affect the incidence of diabetes. The lymphocyte subpopulations were unaffected by these treatments. These data support the hypothesis that decreased beta-cell activity is responsible for the protection against the immune beta-cell destruction.

Spontaneous diabetes mellitus syndrome in the rat. IV. Immunogenetic interactions of MHC and non-MHC components of the syndrome.

We have examined the frequency of three phenotypic characteristics of the syndrome of spontaneous diabetes (overt IDDM, lymphocytic infiltration of the pancreas, and depression of T lymphocytes) in the offspring of crosses between IDDM BB rats and rats of strains with the same and different RT1 genotypes. On the basis of these observations we propose that there are at least three components of the diabetic syndrome in the rat: (1) a requirement for the RT1u haplotype from the BB strain or a gene in close linkage with the gene coding for this haplotype, (2) a susceptibility for development of insular, periductular, or intraacinar lymphocytic infiltration in the pancreas, and (3) a susceptibility to depression of T lymphocytes. Interactions between these components as well as with other genetic and environmental factors contribute to the full expression of the syndrome.

Histological and cytogenetic findings in a malignant tumor of the chest wall and lung (Askin tumor)

This report describes a histological and cytogenetic study of a malignant tumor involving the chest wall and lung (Askin tumor) of a young girl. Although initially considered to represent a variant of Ewings sarcoma, immunocytochemical studies disclosed neuron-specific enolase in neoplastic cells. Ultrastructural study revealed rare cells which contained microtubules and/or dense core neurosecretory type granules. Cytogenetic analysis of neoplastic cells disclosed a reciprocal translocation (11;22) (q24;q12) and occasional extrachromosomal structures interpreted as double minute chromosomes. The latter finding, an indication of gene amplification, is commonly identified in neural crest-derived neoplasms. These ultrastructural, immunocytochemical, and karyotypic data provide evidence in support of a neuroepithelial histogenesis for the Askin tumor.

Further observations on carcinoma in situ of the urinary bladder: Silent but extensive intraprostatic involvement

Of seven patients with carcinoma in situ of the urinary bladder in the absence of an associated papillary carcinoma, five were found to have silent but extensive intraductal prostatic involvement. In three of these the carcinoma in situ was associated with microinvasion. The mean age at the time of diagnosis was 68 years. All had symptoms characteristic of carcinoma in situ, including hematuria, dysuria, and urgency. In three patients the prostatic involvement was diagnosed on transurethral resection. In two it was discovered only after radical cystectomy. The prostatic involvement was neither suspected clinically nor has it been previously emphasized. Although three patients are alive, apparently free of disease up to 15 months postcystectomy, two have died, one of disease. The importance of prostatic assessment in the evaluation of the patient with carcinoma in situ of the urinary bladder is emphasized.

On the ultrastructure of hibernoma

An electron‐microscopic study of hibernoma and a review of the histogenesis, development, and post‐natal structural composition of brown and white adipose tissue are presented. The ultrastructural features of hibernoma include multivacuolated and univacuolated cells containing variable numbers of lipid vacuoles, abundant moderately pleomorphic mitochondria with transverse cristae, lysosomes, lipofuscin granules, pinocytotic vesicles, well‐formed basal lamina, and prominent subplasmalemmal condensations. The latter have not been previously reported in hibernoma, brown adipose tissue or white adipose tissue, although gap junctions have been observed in brown adipose tissue of newborn mice. It is concluded that the ultrastructural observations support the concept proposed decades ago that hibernoma represents the neoplastic counterpart of brown adipose tissue.

Pituitary craniopharyngioma with tooth formation

A classic pituitary craniopharyngioma was removed from the suprasellar and intrasellar regions of a 4‐year‐old boy. In each of 2 separate surgical specimens, a rudimentary tooth was found buried within the tumor. The implication of this finding in characterizing the embryology of the development of the tooth and pituitary is discussed. It is concluded that this tumor arose from tissue which, by the production of a tooth, expressed its fullest capacity of differentiation, and that the craniopharyngioma is developmentally related to the adamantinoma of the jaw.