Aurel Lupulescu

The dermatopathology of Cowden's syndrome*

During the past 2 years we have studied eighty‐nine biopsy specimens from nineteen patients with Cowdens syndrome. Among fifty‐three facial lesions, twenty‐nine were trichilemmomas. Twenty‐ three of the others were consistent with trichilemmoma, showed a non‐specific benign verrucous acanthoma, or were not diagnostic; one was a bluenaevus. All fourteen oral mucosal biopsy specimens were benign fibromas. Nineteen of twenty‐two biopsy specimens from the hands and feet showed the pattern of benign keratosis. Multiple trichilemmomas were found in all patients with Cowdens syndrome, but at times several biopsy specimens were required before a diagnostic picture was un‐ covered. All patients with multiple facial trichilemmomas were found to have Cowdens syndrome. The combination of multiple facial trichilemmomas, oral fibromas, and benign acral keratoses enables one to diagnose Cowdens syndrome at a stage before serious internal complications develop.

Hormones, vitamins, and growth factors in cancer treatment and prevention: A critical appraisal

Hormones, hormone agonists, hormone antagonists, vitamins and their synthetic analogues, and growth factors are currently the most widely used anticancer drugs. Although in many cases they provide dramatic results, in other cases their effects are conflicting. A critical appraisal of the effects of these drugs is needed.

Lung cancer: A transmission and scanning electron microscopic study

Transmission and scanning electron microscopic studies of adenocarcinoma, epidermoid carcinoma, and undifferentiated small cell carcinoma (oat cell carcinoma) of the lung are described and illustrated. This combined study demonstrates some characteristic architectural and ultrastructural changes of the malignant cells valuable for diagnosis and classification of lung tumors. This study also provides a better understanding of the morphology and growth of these common tumors.

Bowen's disease of genital areas. An ultrastructural study.

Ultrastructural changes in specimens removed from Bowens diseased genital areas of five patients are described, and a comparison is made with the tissue from the surrounding normal skin. Electron microscopic findings in Bowens disease include an advanced dyskeratosis, acantholysis due to dissolution of desmosomal‐tonofilament complexes, enlarged nuclei and nucleoli, increased polysome populations, mitochondrial alterations and nuclear inclusions. The basement membrane remains intact. Occasionally, atypical cells are undergoing cytolysis and are engulfed and phagocytized by the neighboring keratinocytes (apoptosis). The normal epithelium at the periphery of the lesion exhibits only a minimal degree of ultrastructural change.

Effect of protective agent against lipid-solvent-induced damages

The ultrastructural and relief (cyto-architectural) changes of human epidermis following exposure to a protective gel and acetone or kerosene were studied in healthy volunteers. Topical applications of acetone and kerosene on unprotected skin produced cell damage and a disorganized pattern in the upper layers of epidermis. The ultrastructural changes following acetone consisted of large paranuclear vacuoles, swollen mitochondria, and clumped tonofilaments. Severe disorganization with intense cytolysis and enlarged intercellular spaces occurred after exposure to kerosene. Scanning electron microscopy revealed edematous connified cells (corneocytes) following acetone exposure, whereas kerosene induced the occurrence of large lacunae in the swollen corneocytes. The application of a protective agent prior to solvent exposure substantially reduced the ultrastructural and relief changes of epidermal cells.

Multiple vascular fibromas and myxoid fibromas of the fingers: A histologic and ultrastructural study

A father and his son were seen because of multiple wartlike lesions on their fingers and palms. On histologic examination, these lesions showed changes compatible with vascular fibromas, myxoid fibromas, and, in a few instances, verruca vulgaris. We are not aware of reports of similar cases in the dermatologic literature.

Ultrastructural studies of xeroderma pigmentosum

Electron microscopic observations of both sun-exposed and sun-protected skin from a black patient with xeroderma pigmentosum (XP) revealed abnormal ultrastructural changes in the melanin pigmentary system, tonofibrillar-desmosome complexes, endoplasmic reticulum, mitochondria, and nucleoli of all keratinocytes. The difference between the cellular changes in the sun-exposed skin and that protected from sunlight was quantitative rather than qualitative in character. The most salient changes were seen in sun-exposed specimens: melanosomes limited by a membrane showed a high degree of polymorphism with a tendency to form large complexes, and many fibroblast-like cells displayed an intense phagocytic activity for melanosomes, the latter finding not previously reported. The present study supports the conclusions of other investigators that XP is a heterogeneous disease. Clarification of the XP entities by continued research may identify the defective gene and lead to methods of correction by the molecular biologist.

Ultrastructural and cell surface changes of human psoriatic skin following Goeckerman therapy.

Ultrastructural and cell surface studies of skin in psoriatic patients prior to and after Goeckerman therapy (crude coal tar and UVB‐light) have demonstrated significant cellular changes following this treatment: hyperactivity of melanocytes with melanosome polymorphism, increase of desmosomes, tonofilaments, keratohyaline granules, a decrease in mitochondria, keratinosomes, polysomes, dark cells and a reduction in size of nuclei and nucleoli. The enlargement of intercellular spaces and the redundancy of basement membrane were also reduced. Langerhans cells were moderately decreased and exhibited a normal ultrastructural pattern. No significant changes in cutaneous nerve distribution or morphology were observed in these cases. Scanning electron microscopy following treatment revealed a regular surface and orientation of corneocytes, with flattened surfaces; and a reduction of their ridges on the surfaces, as well as of the intercellular spaces and red blood cells. These findings indicate that Goeckerman therapy restored the ultrastructural and cell surface pattern in the psoriatic skin by inducing orthokeratinogenesis, development of the tonofïbrillar‐desmosome system, and decrease in mitochondria, nuclei and nucleoli.

Ultrastructural pathology of the thyroid gland

Morbid changes which occur in the human thyroid gland can be understood only from the standpoint of normal histology and physiology of the thyroid. Conventional transmission electron microscopy (TEM), freeze-etching and scanning electron microscopy (SEM) have revealed that the ultrastructural pattern of the normal human thyroid gland is quite similar to normal patterns already described in other mammals (mouse, rat, rabbit, guinea pigs, dogs), resembling especially the thyroid glands of guinea pigs and dogs (1–4). The functional unit is the follicle (Fig. 1). The human thyroid gland is composed of follicles separated by capillaries, lymph vessels, large areas of connective tissue and interfollicular cells (mast cells, fibroblast). Thyroid follicles are heterogenous; some are large, composed of flat cuboidal cells and filled with a homogenous dense colloid; others are small and outlined by columnar cells. No vacuoles can be seen at the periphery of the colloid (Fig. 2). Light microscopic autoradiography further delineates the heterogeneity of the thyroid gland. Radioiodine (131I or 125I) is incorporated differently; fewer grains are seen in the larger follicles compared with smaller, in which a more isotopic incorporation can be seen as mottled grains within the follicular colloid.