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Notes: Cowden's disease is characterized by multiple hamartomas of the skin, breast, thyroid, and gastrointestinal tract. In the past, a viral hypothesis for the keratotic lesions of the skin has led to much controversy. The present study describes the results of a detailed fine structural analysis of 10 hyperkeratotic extremity lesions and 2 keratotic lesions from the face of a patient with Cowden's disease. Increases in the keratinocyte population were primarily confined to the basal and suprabasal regions. Differentiation products characteristic of keratinization were normal in both quantity and appearance. Nuclear remnants and number-ous lipid droplets, markers of abnormal keratinization, were noted within horny cells. However, viral particles and/or virus-like particles were not observed in keratinocytes. Melanocytes and Langerhans cells were numerous. The latter contained membrane-bound pigment vacuoles in addition to the characteristic Birbeck granules. These unusual Langerhans cells were observed in the dermis as well as the epidermis. A large number of fully granulated ‘resting” mast cells was uniformly distributed throughout the dermis, associated with a prominent cellular infiltrate. Our observations do not support the concept of a viral etiology for these tumors.

Notes: Recent observations indicate that stem cells of the murine hair follicle exist exclusively as a subpopulation of relatively undiffer-entiated outer root sheath cells located in the bulge region at the mid-portion of the follicle. Because it has been hypothesized that stem cells of interfollicular epidermis may represent targets of cytotoxic responses in acute graft-versus-host disease (AGVHD), we studied murine AGVHD and observed sequential skin biopsies for the presence and evolutionary pattern of follicular injury. Highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW-〉B6 strain combination, only CD8+ effector cells produced histologic evidence in skin of AGVHD, which peaked three weeks post-transplant. In the B10.D2-〉DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, GD8+ cells, mediated disease, which peaked during the fourth week posttransplant. Analysis of skin from both strain/effector cell combinations revealed follicular infiltrates preferentially involving follicular stem cell (FSC) regions (bulge) of anagen follicles between the second and third weeks post-transplant. These infiltrates often preceded infiltration of adjacent interfollicular epidermis and were associated with follicular involution to telogen (resting) phase. By the fourth week post-transplant, 〉 50% of follicles were in telogen phase and residual inflammation was minimal. This provided a unique opportunity to observe follicular recovery from telogen. This involved formation of buds of premordial hair matrix derived from FSC populations of the bulge regions, and subsequent descent of these buds, initially tethered by elongate columns of putative stem cell progeny, along the course of fibrous tracts corresponding to follicular sheaths. These findings suggest that stem cells of hair follicles, as well as epidermis, represent potential targets of cytotoxicity in AGVHD. Moreover, they provide in vivo demonstration that the newly-described FSC population of the follicular bulge give rise to germinative matrix epithelium upon pathological stimulation.

Notes: An ultrastructural study of eccrine sweat glands was carried out on three patients with iron overload (two with idiopathic haemochromatosis and one with transfusional haemosiderosis). In all three patients small electron-dense particles were seen in both eccrine sweat glands and macrophages. They appeared primarily in the clear cells of the eccrine sweat glands as membrane-bound irregularly shaped bodies, and were shown to contain iron by energy dispersive X-ray microanalysis. Iron aggregates in and around sweat glands were also seen on light microscopy.

Notes: The histopathology of striae distensae is disputed; different authorities give contradictory accounts of the microscopic changes, especially in elastic fibres.We re-evaluated the problem by taking eight elliptical biopsies across striae. Six were examined by light microscopy with appropriate stains for elastin and collagen. Two were prepared for scanning electronmicroscopy (s.e.m.), using a procedure which removes collagen, enabling the elastic network to be seen in its native form.By light microscopy, striae were sharply demarcated from normal skin, consisting mainly of fine, straight bundles of collagen arranged parallel to the surface. Fine elastic fibres were disposed similarly without fragmentation, fraying or curling.By s.e.m., the elastic network was found to be extraordinarily dense and well developed with many fine, curled fibres in random array. It was evident that the routine stains for elastin greatly underestimated the abundance of elastic fibres, probably because immature fibres contain insufficient protein matrix. The horizontal packing of collagen bundles was confirmed by s.e.m.These findings support the view that striae distensae are scars. There is no evidence that they form by stress-induced rupture of the connective tissue.