Robert G. Freeman

On the Pathogenesis of Pseudoepitheliomatous Hyperplasia

Examples of acanthosis of epithelium of skin appendages are illustrated and a concept of pathogenesis of some instances of pseudoepitheliomatous hyperplasia from acanthotic appendages is presented.

Cutaneous defects of focal dermal hypoplasia: an ectomesodermal dysplasia syndrome

The 5 major cutaneous defects of development found in focal dermal hypoplasia, an ectomesodermal dysplasia syndrome, are: aplasia cutis congenita, multiform atrophy‐like areas, striate, papillomatous, and lipomatous lesions of skin. Subepidermal lipomatosis, present in some lesions, has been reported to be due to absence of dermis or a striking underdevelopment of connective tissue with replacement by adipose tissue from herniation of subcutaneous fat through multiple areas of hypoplasia. We believe this theory to be a major error in interpretation of the microscopic findings. We have had the unique experience of studying 2 patients periodically for 27–30 years and 2 additional patients for a shorter time. Biopsy specimens were removed at intervals for analysis from the same or similar lesions (43 specimens) from these 4 individuals. Our evidence strongly supports the concept that the cutaneous defects of development involving‐fat cells represent heterotopic fat i.e. a fat nevus resulting from dysplasia, not hypoplasia followed by herniation of subcutaneous fat.

Benign non-X histiocytosis: A unique case bridging several of the non-X histiocytic syndromes

We present a patient with a papular eruption of 4 years duration that clinically resembled xanthoma disseminatum or the indeterminate cell disorder. On light microscopy his disorder resembled generalized eruptive histiocytoma or the indeterminate cell disorder. Special stains, cultures, and electron microscopy were noncontributory. Indirect immunofluorescence studies with monoclonal antibodies to cell surface markers demonstrated infiltrating cells of monocyte/macrophage lineage (OKM1, MAC-1, HLA-DR, and HLA-DQ positive) rather than Langerhans or indeterminate cell lineage (OKT6 negative). This case may overlap two or more of the previously reported non-X histiocytic syndromes, suggesting that perhaps these syndromes should be viewed as a spectrum of disease rather than as discrete entities. We recommend performing cell phenotyping on all new cases of non-X histiocytosis because clinical, microscopic, and ultramicroscopic findings often prove inadequate for classification.

Structure and significance of the pits with their tumors in the nevoid basal cell carcinoma syndrome

Parallel histopathologic, histochemical, scanning, and transmission electron microscopic (EM) observations were made on palmar pits of one patient and on palmar pits, with an unprecedented number of basal cell carcinomas. of another patient. The first scanning view of tumor growing into the lumen of a pit from the genetically defective epidermis below is presented. The anatomy of the pit is demonstrated for the first time by scanning view of a transected pit. Our observations confirmed those of Hashimoto et al on the mechanisms involved in premature desquamation of the stratum corneum and on the true nature of the epithelium at the base of the pit. This epithelium resembled closely basal cell epithelioma and represented carcinoma in situ. The striking demarcation afforded by the axure B stain of normal and abnormal portions of the palmar epidermis with pit and the poor stainability of the pit with tumor was likewise confirmed. The tumors exhibit aggressive behavior infrequently.

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 (DBS) 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.

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.

Wrinkling due to mid-dermal elastolysis: two cases and literature review.

Background: Mid-dermal elastolysis is an acquired disorder of elastic tissue clinically characterized by diffuse fine wrinkling, most often of the trunk and arms. Histologically, a clear band of elastolysis is present in the mid-dermis. Objective: Although examples of diffuse elastolysis are well known, only a small number of patients with mid-dermal elastolysis have been reported to date. We present two patients with clinical and histological evidence of mid-dermal elastolysis, review the literature, and summarize the salient features of some common disorders of elastic tissue. Methods: The first patient presented with fine wrinkles and papules over the upper arms, upper chest, and axillae, and demonstrated increased laxity of the eyelids. The second patient had striking wrinkles extending in a band-like pattern on her arms, upper chest, back, and abdomen. Neither one of our patients had a previous history of skin inflammation, urticaria, or any other underlying diseases related to their skin changes. Skin biopsies were taken from lesional and perilesional skin of both patients, and were stained with hematoxylin and eosin, and with elastic tissue stain. In addition, a tissue sample from Patient 1 was fixed for electron-microscopy. Results: Hematoxylin and eosin stains did not demonstrate specific changes or diagnostic patterns. However, elastic tissue stains revealed a band-like loss of elastic tissue in the mid-dermis. Elastic tissue in the remaining superficial and deep dermis stained normally. Electron-microscopy was consistent with these findings and revealed significant loss of elastic tissue limited to the mid-dermis. Conclusion: We have presented two cases of mid-dermal elastolysis and reviewed the literature. To date, the pathophysiology of mid-dermal elastolysis had not been elucidated and no definitive therapy exists.

Topical 5-fluorouracil treatment of superficial basal cell epithelioma. A light and electron microscopic study.

A 27‐year‐old patient developed superficial basal cell epitheliomas approximately 20 years after taking Fowlers solution. One of the lesions was successfully treated with topical 2% 5‐fluorouracil solution under occlusion. Sequential biopsies of the lesion before, during and after therapy were examined by light and electron microscopy, and the changes at various stages are described. Changes occurred only in tumor cells and adjacent epidermis, and only after occlusion of 5‐FU. After one week of occlusive therapy, focal discontinuities in the basal lamina and intercellular spaces were wider with reduction and condensation of tonofilaments. Mitochondrial degeneration was seen along with irregularities in nucleoli. These changes were most prominent after two weeks of occlusive therapy, and many degenerating keratinocytes were seen detached from other cells. One month after cessation of therapy, the entire area was excised, and no evidence of tumor was seen.