George W. Elgart

Comparative structural analysis of desmoplakin, bullous pemphigoid antigen and plectin: members of a new gene family involved in organization of intermediate filaments

Desmoplakins (DP) and bullous pemphigoid antigen (BPA) are major plaque components of the desmosome and hemidesmosome, respectively. These cell adhesion structures are both associated intimately with the intermediate filament (IF) network. Structural analyses of DP and BPA sequences have indicated that these molecules are likely to form extended dumbbell-shaped dimers with a central rod and globular end domains. Recent sequence data have indicated that the N-terminal domains of both DP and BPA (like their C-terminal domains) are highly related: the former contain regions of heptad repeats that are predicted to form several alpha-helical bundles. Comparisons of DP and BPA protein sequences with that of plectin (PL), a 466 kDa IF-associated protein, have also revealed large scale homology. Identities between their N-terminal domains are: DP:BPA = 35%, DP:PL = 32%, BPA:PL = 40%, suggesting that BPA is more closely related to PL than DP in this region. In the C-terminal domains, which contain a 38-residue repeating motif, however, DP and PL are closer relatives (identities: DP:BPA = 38%, BPA:PL = 40%, DP:PL = 49%). The central domains of all three proteins have extensive heptad repeat substructure, express the same periodic distribution of charged residues, and are predicted to form two-stranded alpha-helical coiled-coil ropes. These observations suggest that DP, BPA and PL belong to a new gene family encoding proteins involved in IF organization.

Treatment of pyoderma gangrenosum with cyclosporine: Results in seven patients

The mainstay of therapy for pyoderma gangrenosum has been corticosteroids, but many patients respond poorly. During the past 2 years we have treated seven patients who had pyoderma gangrenosum with cyclosporine after their condition proved resistant to conventional therapy. No evidence of permanent toxicity from cyclosporine was detected and treatment with other immunosuppressive agents was discontinued in five of seven cases. Tuberculosis was reactivated in one patient. Three patients had a remission, three had an intermediate response, and one did not respond. These results indicate that cyclosporine is useful in the treatment of patients with refractory pyoderma gangrenosum and suggest an immune mechanism in the pathogenesis of this disorder.

Is there a special relationship between CD30‐positive lymphoproliferative disorders and epidermal proliferation?

The relationship between CD30+ lymphoma and epithelial proliferations is not well defined. CD30+ lymphoma and lymphomatoid papulos (LyP) share immunohistochemical epitopes and some other features. A single case of LyP associated with multiple keratoacanthomas (KAs) was recently reported. We report two cases of atypical lymphocytic proliferation with features of CD30+ lymphoma and LyP intimately associated to KA and squamous cell carcinoma (SCC), KA type. This similar combination of an epidermal tumor and apparent involvement with atypical lymphocytic infiltrates raises the possibility of an association between the two entities. We speculate that the association may be more than expected to occur by chance and suggest several mechanisms by which the association may evolve.

Cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Report of a case and discussion of the origin of pseudoepitheliomatous hyperplasia

We report a case of cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and may complicate the diagnosis of cutaneous melanoma. This diagnostic pitfall is important to both recognize and be cognizant of, so as to avoid diagnostic errors. The observation of the pseudoepitheliomatous hyperplasia, in this case with an extensive proliferation of eccrine ducts, provides further evidence that cutaneous pseudoepitheliomatous hyperplasia arises within the eccrine apparatus.

Postoperative pressure‐induced alopecia: report of a case and discussion of the role of apoptosis in non‐scarring alopecia

We report a case of postoperative pressure induced alopecia in a 21‐year‐old black female after multiple intraoperative procedures. The histopathology is distinctive and demonstrated features in common with trichotillomania and alopecia areata, including the presence of pigment casts, catagen follicles, melanophages and apoptotic bodies. External hair manipulation is considered the primary event in the etiology of pigment casts, however, our present case demonstrated numerous pigment casts despite a complete lack of evidence of external hair manipulation. We performed pattern analysis and in situ end‐labeling in 19 cases of non‐scarring alopecia. Pigment casts were seen in postoperative alopecia (1 case), alopecia areata (1 case) and trichotillomania (5 cases). These forms of alopecia have in common the sudden termination of the anagen phase of the hair cycle. When the anagen portion of the hair cycle is prematurely disrupted hairs enter into catagen. Pigment casts may represent a non‐specific reaction pattern of follicles that are suddenly transformed from anagen to catagen. We therefore propose that hair manipulation is not uniquely responsible for the formation of pigment casts. The primary pathophysiology resulting in the formation of pigment casts more correctly reflects the sudden termination of the anagen phase of the hair cycle.

High Proliferative Activity Excludes Dermatofibroma: Report of the Utility of MIB-1 in the Differential Diagnosis of Selected Fibrohistiocytic Tumors

CONTEXT Dermatofibroma is a benign fibrohistiocytic tumor composed of a mixture of fibroblastic and histiocytic cells. The diagnosis of this tumor is generally uncomplicated; however, rare variants may be difficult to distinguish from malignant fibrohistiocytic tumors. Deep penetrating dermatofibroma may be difficult to distinguish from dermatofibrosarcoma protuberans, and pseudosarcomatous dermatofibroma and dermatofibroma with monster giant cells share morphologic similarities with malignant fibrous histiocytoma and atypical fibroxanthoma. OBJECTIVE To find an immunohistochemical marker or markers that differentiate between fibrohistiocytic lesions of skin. DESIGN We evaluated the immunophenotypic characteristics of 83 fibrohistiocytic tumors (36 typical dermatofibromas, 16 cases of dermatofibrosarcoma protuberans, 16 malignant fibrous histiocytomas, and 15 atypical fibroxanthomas) using antibodies against MIB-1 (Ki-67), factor XIIIa, CD34 (HPCA-1), HHF35 (muscle-specific actin), 1A4 (smooth muscle actin), cytokeratin (AE1/AE3, CAM 5.2, and 34betaE12), S100 protein, and desmin. RESULTS A high proliferative index detected by MIB-1 staining excluded the possibility of dermatofibroma and was diagnostically useful in separating this entity from dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and atypical fibroxanthoma. A low proliferative index, however, could not differentiate dermatofibroma from dermatofibrosarcoma protuberans. Factor XIIIa reactivity was not helpful for the diagnosis of dermatofibroma, whereas CD34 reactivity was statistically significant in the diagnosis of dermatofibrosarcoma protuberans. The sensitivity of these 2 markers is low and therefore of questionable practical diagnostic value. CONCLUSION Evaluation of the proliferative index may further assist in distinguishing dermatofibroma from dermatofibrosarcoma protuberans, atypical fibroxanthoma, and malignant fibrous histiocytoma.

Potential Role of Human Growth Hormone in Melanoma Growth Promotion

BACKGROUND Human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the malignant transformation and progression of a variety of cancers. HGH is also known to upregulate molecular signaling pathways implicated in the pathogenesis of melanoma. Although HGH has previously been implicated in promoting the clinical growth of both benign and malignant melanocytic neoplasms, to our knowledge there are no conclusive studies demonstrating an increased risk of melanoma following HGH therapy. Nevertheless, there are reports of melanoma developing subsequent to HGH coadministered with either other hormones or following irradiation. OBSERVATION A 49-year-old white man presented with a new pigmented papule that was diagnosed as melanoma. The patient reported using HGH for 3 months prior to the diagnosis. His 51-year-old wife, who also was white, had also been using exogenous HGH for 3 months and had been diagnosed as having a melanoma 2 weeks prior. CONCLUSIONS Given the unlikelihood of 2 unrelated people developing melanoma within a short time span, it is reasonable to assume that a common environmental component (HGH or other shared exposure) contributed to the development of both melanomas. Because of the increased use of exogenous HGH as an antiaging agent, it is important to be aware of the growth-promoting effects of this hormone. Until better data are available that determines the true risk of exogenous HGH, its use as an antiaging agent merits increased surveillance.

Coma blisters in two postoperative patients.

Coma blisters are self-limited cutaneous bullae that occur in the setting of loss of consciousness because of a drug, illness, or accident, with the most common settings being barbiturate overdose and neurological disorders. The etiology behind coma blisters is poorly understood and is not related to underlying infections or autoimmune conditions. The clinical presentation consists of bullae, erosions, and violaceous plaques usually involving sites of pressure. The skin lesions usually occur within 48-72 hours of the start of a coma and resolve within 2-4 weeks. We present one case of a 5-month-old infant with severe valvular disease who required surgical repair. He was placed on extra corporeal membrane oxygenation and developed multiple tense coma blisters during the course of therapy. Skin biopsy revealed a noninflammatory subepidermal blister with necrosis of the overlying epidermis and necrosis of the eccrine ducts. We also present a second case of an 18-year-old female patient who underwent surgical resection of a benign mandibular tumor. She subsequently developed bullae on both arms 4 days after surgery. The skin biopsy showed a necrotic epidermis, a subepidermal blister, and diffuse necrosis of the eccrine coils.

Erythema multiforme major associated with CMV infection in an immunocompetent patient.

Background: Cytomegalovirus (CMV) infection usually remains asymptomatic in immunocompetent adults, and few cases of complicated disease in nonimmunosuppressed patients have been reported. Erythema multiforme (EM), an acute and self-limiting skin eruption characterized by a typical targetoid lesion that may also affect the mucosa, is a hypersensitivity reaction that usually occurs after herpes simplex virus infection or use of certain drugs and resolves without complications in healthy individuals. To our knowledge, CMV infection has been associated with EM in only six patients. Objective: We present a case of an EM caused by CMV infection in a 35-year-old nonimmunosuppressed patient who was successfully treated with ganciclovir. Conclusion: Our report, like other similar reports found in the literature, suggests that CMV can trigger EM in apparently healthy individuals. Intravenous ganciclovir appears to be a good treatment option in these cases.

Confocal Microscopy of Challenging Dermoscopic Diagnoses

D ERMOSCOPIC EVALUATION HAS BEEN shown to reduce unnecessary biopsies and to increase the accuracy of melanoma diagnosis. However, some lesions remain dermoscopically challenging, as in the 3 paired malignant and benign cases shown in the Figure: A and B reveal a disorganized reticular pattern and a moth-eaten border; C and D reveal structureless areas and areas of gray and asymmetrical dots; and E and F reveal a disorganized reticular pattern, structureless areas, and areas of gray and moth-eaten borders. Reflectance confocal microscopy provides additional information that can serve to facilitate the correct diagnosis. Please go to http://www.archdermatol.com to view the confocal features and diagnosis for each of these cases (eFigures). Confocal microscopy also reveals some lesion structural details that are not readily appreciated by standard histopathology. This is particularly evident for the extension of melanocytic dendrites and for the presence of retractile (presumably melanocytic) cells in the papillary dermis residing under some histologically diagnosed in situ melanomas.