Edward H. Bossen

Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases.

Ten cases of an unusual form of carcinoma involving the mucosa and underlying tissue of the tongue, hypopharynx, and larynx are described. All ten of the tumors were evaluated by light microscopy; five were also studied by electron microscopy. The major histopathologic feature is carcinoma with a basaloid pattern in intimate association with squamous cell carcinoma, carcinoma in situ, or focal squamous differentiation. The basaloid tumor consists of small crowded cells with hyperchromatic nuclei, scant cytoplasm, small cystic spaces, and foci of tumor necrosis. Prominent hyalinosis is evident. Ultrastructurally, the basaloid epithelial cells possess rare tonofilaments and varying amounts of desmosomes. The cystic spaces contain either loose stellate granules or replicated basal lamina arranged in parallel stacks or globoid masses. This unique tumor was found to be highly malignant, with histologically proved metastases in 80 per cent of the cases. Most of the patients were treated by radical surgery supplemented with radiation and/or chemotherapy. It is concluded that tumors with these characteristic features constitute a distinct histopathologic entity, not previously described, for which basaloid-squamous carcinoma is an appropriate term.

Characterization of pre- and post-treatment pathology after enzyme replacement therapy for pompe disease

In Pompe disease, a genetic deficiency of lysosomal acid α-glucosidase, glycogen accumulates abnormally in the lysosomes of skeletal, cardiac and smooth muscle, and contributes to clinically progressive and debilitating muscle weakness. The present study involved 8 infantile-onset Pompe patients, treated weekly with 10 mg/kg of recombinant human acid α-glucosidase (rhGAA). Muscle biopsies were obtained at baseline, 12 and 52 weeks post-treatment to establish an indicator of efficacy. Several histologic strategies were employed to characterize changes in pre- and post-treatment samples, including high-resolution light microscopy and digital histomorphometry, electron microscopy, capillary density and fiber type analysis, and confocal microscopy for satellite cell activation analysis. Histomorphometric analysis was performed on muscle samples to assess glycogen depletion in response to enzyme replacement therapy (ERT). The extent of glycogen clearance varied widely among these patient samples, and correlated well with clinical outcome. Low glycogen levels, mild ultrastructural damage, a high proportion of type I fibers, and young age at baseline were all features associated with good histologic response. There was no correlation between capillary density and glycogen clearance, and activated satellite cell levels were shown to be higher in post-treatment biopsies with poor histologic responses. This histopathologic study of infantile Pompe disease provides detailed insight into the cellular progression of the disease and its response to therapy while highlighting a number of methodologies which may be employed to assess regression or progression of the associated pathology. As enzyme replacement therapy becomes more prevalent for the treatment of lysosomal storage diseases, such evaluation of post-treatment pathology will likely become a more common occurrence in the daily practice of pathologists.

The management of desmoid tumors

PURPOSE To determine the efficacy of different treatment modalities for desmoid tumors. MATERIALS AND METHODS We reviewed the treatment of 40 patients with histologically confirmed desmoid tumors seen at Duke University Medical Center between 1974 and 1990. RESULTS Radiotherapy was administered to 16 patients (Group I)--14 with recurrent disease s/p surgery and in two as initial treatment. The average size of the irradiated lesions was 9.3 +/- 3.9 X 8.4 +/- 3.5 cm. With a median follow-up of 57.5 months and a median administered dose of 5400 cGy (mean 5286 cGy, range 4960-5620 cGy), local control has been obtained in 15/16 patients (94%). Complete regression (5/16), partial regression (5/16), or stable disease (5/16) was produced in 15 patients while one patient failed and was salvaged via gross total resection. Continued regression has been seen up to 60 months after treatment. Fourteen patients underwent primary gross total resection and two underwent subtotal resection (Group II). None received post-operative radiotherapy. Three of 14 patients (21%) recurred after gross total resection. All three were salvaged with subsequent gross total resection. After subtotal resection, 2/2 patients recurred. With a mean follow-up of 52 months, 14 patients are without evidence of disease, one is dead with disease (unrelated cause of death), and one was lost to follow-up after recurrence. Eight patients have been treated with combinations of chemotherapy, NSAIDS, anti-estrogens, and immunotherapy with mixed results (Group III). A subset of seven patients with retroperitoneal disease taken from all three groups had large tumor burden (mean size 17 X 15 cm), an infiltrative nature, as well as a difficult location. The disease was surgically resectable in three patients. One is without evidence of disease 9 years after gross total resection alone. Disease has been stabilized with radiotherapy in the other two patients after multiple unsuccessful surgical resections. Of four patients with unresectable disease, two are dead of disease, one died of unrelated causes with disease, and regression of disease was obtained in the other with Gamma-interferon after unsuccessful treatment with tamoxifen and vincristine, doxorubicin, and cyclophosphamide chemotherapy. CONCLUSION Gross total resection is the indicated initial therapy, if it can be performed without significant disfigurement. Radiotherapy is also excellent for obtaining local control, even in patients with a large burden of recurrent disease. Doses in the range of 50 to 55 Gy give a chance of local control equal to that obtained with higher doses previously reported.

Comparative stereology of the mouse and finch left ventricle

The volume fractions and surface per unit cell volume of some subcellular components of the left ventricles of the finch and mouse were quantitated by stereologic techniques. These species were chosen for study because they have similar heart rates but differ morphologically in some respects: fiber diameter is larger in the mouse; the mouse has transverse tubules while the finch does not; and the finch has a form of junctional sarcoplasmic reticulum (JSR), extended JSR (EJSR), located in the cell interior with no direct plasmalemmal contact, while the mouse interior JSR (IJSR) abuts on transverse tubules. Our data show that the volume fraction (Vv) and surface area per unit cell volume (Sv) of total SR, and free SR (FSR) are similar. The volume fractions of mitochondria, myofibrils, and total junctional SR were also similar. The Sv of the cell surface of the finch was similar to the Sv of the cell surface of the mouse (Sv-plasmalemma plus Sv of the transverse tubules). The principal difference was in the distribution of JSR; the mouse peripheral JSR (PJSR) represents only 9% of the total JSR, while the finch PJSR accounts for 24% of the birds JSR. The similar volume fractions of total junctional SR (PJSR + EJSR in the finch; PJSR + IJSR in the mouse) suggest that the EJSR is not an embryologic remnant, and raises the possibility that some function of JSR is independent of plasmalemmal contact.

Benign vaginal rhabdomyoma: a light and electron microscopic study.

A benign vaginal rhabdomyoma from a 49‐year‐old woman was examined by light and electron microscopy. While many of the ultrastructural features conformed to those noted in previously described rhabdomyomas, certain features are described for the first time. These include attachment plaques between cells enclosed within a common basement membrane, cytoplasmic bodies, and peripheral couplings. Finally, the literature is reviewed and the reported cases of rhabdomyoma are divided into adult and fetal types based upon light microscopic criteria.

Acute pancreatitis in an infant with lactic acidosis and a mutation at nucleotide 3243 in the mitochondrial DNA tRNALeu[UUR] gene

The A to G point mutation at position 3243 of the mitochondrial DNA tRNALeu(UUR)gene is commonly found in patients with the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). A male patient was referred at 7 months with failure to thrive, developmental delay, microcephaly and hypotonia since age 2 months. He had developed lactic acidosis and increasingly frequent seizures since age 5 months. The patient was admitted at 15 months with pleural and pericardial effusions, which resolved. Three weeks later he developed evidence of pancreatitis with hyperglycemia, sudden profound increase in lactic acidosis and increased serum lipase. He died unexpectedly the next day of cardiorespiratory collapse following an acute gastro-intestinal hemorrhage. Analysis of mitochondrial DNA (mtDNA) in muscle showed heteroplasmy for the mutation MTTL1*MELAS3243G (> 95%). Infants with this mutation commonly present with failure to thrive, significant developmental delay, and hypotonia, while stroke-like episodes occur later in survivors. They usually have lactic acidosis and a high percentage of mutant mtDNA in muscle.

Adenoid cystic carcinoma of the breast metastatic to the kidney. A clinically symptomatic lesion requiring surgical management

Adenoid cystic carcinoma (ACC) of the breast is a rare histologic type of breast cancer associated with a good prognosis. A woman who earlier had a pulmonary metastasis surgically resected 6 years postmastectomy developed clinically symptomatic bleeding from a renal metastasis 12 years postmastectomy. An atypical angiographic picture (moderate vascularization) for secondary renal neoplasms was observed. The characteristic histologic features of ACC were present in all specimens; ultrastructural characteristics of ACC were identified in the renal lesion. Successful surgical management of these metachronous solitary metastases demonstrates the therapeutic utility of aggressive management in maintaining disease control of this histologic type of breast cancer.

Comparative stereology of mouse atria

The left and right atria of the mouse were compared to each other and to the mouse left ventricle using stereologic techniques. The volume fraction (Vv) and surface area per unit cell volume (Sv) of the interior junctional sarcoplasmic reticulum (IJSR), total JSR and extended JSR were greater in the left atrium than in right. The Vv and Sv of the free SR, transverse tubules, and mitochondria were similar in the two atria. It is suggested that the differences in junctional sarcoplasmic reticulum between the atria can be accounted for by a difference in distribution of two types of cells whose anatomy is analogous to working and conducting fibers in the ventricle. The Sv and Vv of the transverse tubules, mitochondria, and all the components of the sarcoplasmic reticulum except for the free SR were greater in the left ventricle than in either atrium. The greater calcium content and sensitivity to extracellular calcium of the atria may explain the greater volume of free SR in the atria as compared to the left ventricle. The Sv of the plasmalemma of the atria and of the Sv of the plasmalemma of the transverse tubules of the left ventricles supports the suggestion of others that there is a constant ratio of surface area to cell volume in cardiac cells.

Comparative stereology of the lizard and frog myocardium.

The atria and ventricles of the frog and lizard were quantitated using stereologic techniques. The volume fraction (Vv) and surface density (Sv) of the free, junctional and total sarcoplasmic reticulum and mitochondria of the lizard atrium and ventricle were greater than in the corresponding chambers in the frog. Myofibrillar volume fraction and plasmalemmal surface density did not differ between the two species. The volume fraction and surface density of the free and total SR, and myocardial granules were greater in the lizard atrium than ventricle but the myofibrillar Vv and mitochondrial Vv and Sv were less. The Sv of the free SR, total SR, and the Vv and Sv of myocardial granules of the frog atrium were greater than in the frog ventricle. There were no differences between myofibrils and mitochondria in the frog atrium and ventricle.

Ceruminous gland adenocarcinoma. A light and electron microscopic study

Tumors of ceruminous gland origin in the external auditory canal are rare in man. A case is described in which such a tumor presented as an invasive vascular temporal bone neoplasm, mimicking a glomus jugulare tumor. Light and electron microscopic study of this tumor confirmed a diagnosis of ceruminous gland adenocarcinoma. Tumors of ceruminous gland origin appear to have a distinctive clinical behavior by virtue of their unique anatomical location in the external auditory canal. Our experience with this case establishes another clinical picture characterizing the histologic type of ceruminoma designated as a ceruminous gland adenocarcinoma. We feel that the generic term „ceruminoma,”︁ with its implied histologic subgroups, is useful to the clinician when he encounters a tumor arising from the modified sweat glands of the external auditory canal.