Detection of intraepidermal malignant melanoma in vivo by confocal scanning laser microscopy.

The early detection of malignant melanoma remains challenging for physicians. New techniques are being explored in order to improve diagnostic accuracy. Confocal scanning laser microscopy (CSLM) represents one such novel imaging modality. It allows in vivo microscopic analysis of skin lesions at a level of resolution approaching histological detail. Therefore, interpretation of optical sections represents in principle a histopathological analysis. Pigmented lesions are particularly amenable to examination by CSLM, since melanin pigment provides endogenous contrast, facilitating the recognition of melanocytes and their distribution within the epidermis. As a first step to explore the use of CSLM in the detection of melanoma, we sought to determine whether images obtained by CSLM are suitable for analysis by established histopathological criteria for the diagnosis of melanoma. We examined five pigmented lesions clinically suspicious for melanoma from five individual patients. Following imaging by CSLM, the clinical lesions were excised for examination by conventional histology. The melanocytes in the confocal images were recognized within the epidermis by their bright cytoplasmic signal intensity. They were round to oval in shape and frequently showed dendritic processes of various lengths. Confocal images of melanoma showed an increased number of intraepidermal melanocytes in solitary units at all layers of the epidermis, including the upper spinous and granular cell layers. Our results demonstrate that intraepidermal melanoma can be recognized by CSLM through analysis of the intraepidermal growth patterns of melanocytes using the same criteria as established for conventional histology. Thus, the application of CSLM represents a new tool for non-invasive screening of intraepidermal pigmented lesions in vivo and offers the opportunity to bring histopathological analysis to the bedside.

Regional magnetic fields as navigational markers for sea turtles.

Young loggerhead sea turtles (Caretta caretta) from eastern Florida undertake a transoceanic migration in which they gradually circle the north Atlantic Ocean before returning to the North American coast. Here we report that hatchling loggerheads, when exposed to magnetic fields replicating those found in three widely separated oceanic regions, responded by swimming in directions that would, in each case, help keep turtles within the currents of the North Atlantic gyre and facilitate movement along the migratory pathway. These results imply that young loggerheads have a guidance system in which regional magnetic fields function as navigational markers and elicit changes in swimming direction at crucial geographic boundaries.

Clinicopathologic variants of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinomas (SCC) are one of the most common malignancies, which, with early recognition, may be curable. These tumors represent a broad spectrum of disorders with many significant clinical, morphologic, and etiologic distinctions. The objective of this article is to review the important clinicopathologic features of SCC with particular emphasis on important recent developments, practical application, and their relevance to the practice of pathology. The most pertinent literature of the last 5 years was reviewed and capsulized. Appropriate histologic interpretation and clinical management of patients with cutaneous SCC requires a comprehensive understanding of the latest advances in the broad field of dermatopathology. Squamous cell carcinoma of the skin represents a complex group of disease subtypes, each with its own characteristics, which may influence morphologic diagnosis as well as treatment and clinical management.

A conceptual shift in the grading of meningiomas.

Grading schemes for meningiomas have traditionally designated tumors as "meningioma," "atypical meningioma," or "anaplastic (malignant) meningioma," depending upon the presence of histopathologic features thought to indicate aggressive behavior. In the past, most systems have considered brain invasion by tumor as the best evidence of malignancy. Perry et al. have recently investigated the significance brain invasion as a prognostic feature in meningiomas. The authors studied a series of 116 patients who had been diagnosed previously with "malignant meningioma" due to the presence of brain invasion, histologic anaplasia, or metastasis. On the basis of a multivariate analysis of histopathologic features and their relationship to tumor recurrence and patient survival, the authors concluded that brain invasion should be considered one of the diagnostic features of atypical meningioma. Accordingly, the diagnosis of malignant meningioma should be reserved for those tumors that are frankly anaplastic and/or contain (> = 20 mitoses per 10 high-power fields (HPF). Due in large part to the strength of evidence in this study, the World Health Organization (WHO) has adopted a grading scheme for meningiomas that incorporates many of the authors' proposals. New diagnostic criteria will result in improved reproducibility with fewer diagnoses of malignant meningioma (WHO grade III).

Bcl-2: bax and bcl-2: Bcl-x ratios by image cytometric quantitation of immunohistochemical expression in ovarian carcinoma: correlation with prognosis.

Bcl-2 is a proto-oncogene which is involved in prolonging cell survival by inhibiting programmed cell death. Bax and bcl-x are members of the bcl-2 family; when overexpressed, they can counteract the ability of bcl-2 to inhibit apoptosis. This suggests a model in which the ratios of bcl-2 to bax and bcl-x can be used to determine response to therapy and prognosis. The expression of bcl-2, bax and bcl-x was studied in 50 ovarian carcinomas. The percentage of positive area immunostained (PPA) in the nucleus and cytoplasm of each ovarian carcinoma was quantitated in 15 high power fields by image cytometry. The ratios were obtained by dividing the PPA of bcl-2 by the PPA of bax and bcl-x. 17 of 50 ovarian carcinomas (34%) stained positively for bcl-2, 39 for bax (78%) and 47 for bcl-x (94%). Although there is no significant statistical correlation between expression of bcl-2, bax or bcl-x and grade (P = 0.15; P = 0. 47; P = 0.56), stage (P = 0.71; P = 0.6; P = 0.42), and overall or disease-free survival (P = 0.26; P = 0.55; P = 0.16), increased bcl-2 expression was demonstrated in patients with shortened overall and disease-free survival. Also, increased expression of bax and bcl-x was associated with increased overall and disease-free survival. Bcl-2:bax and bcl-2:bcl-x ratios less than 1 are associated with survival advantage, although not statistically significant (P = 0.83; P = 0.93). Image cytometric measurement of bcl-2, bax, and bcl-x expression is feasible. There is a tendency for their expression to correlate with prognosis in ovarian carcinomas.

Synthesis and secretion of low molecular weight cuticular proteins during heat shock in the tobacco hornworm, Manduca sexta.

In the tobacco hornworm, Manduca sexta, heat shock normally elicits synthesis of the classic heat-shock proteins. A 1-hr heat shock of 42 degrees C and above can also increase the relative synthesis of certain 12-18 kD proteins in the epidermis. These 12-18 kD proteins were identified as cuticular proteins for several reasons. Like cuticular proteins, they appear only in the epidermis. They can be precipitated from epidermal homogenates with an antiserum to larval cuticle. The same conditions that increased labeled 12-18 kD proteins in the epidermis also increased labeled 12-18 kD proteins in the cuticle. Some of the epidermal increase may result from a partial inhibition of secretion to the cuticle during 46 degrees C heat shock, causing abnormal accumulation in the epidermis. However, slight increases also occur at lower temperatures, which do not inhibit secretion detectably. Preliminary results also indicate that total quantities of at least one cuticular protein mRNA may increase during heat shock, either because of increased transcription or increased mRNA stability.