Immunohistochemical evaluation of toxic epidermal necrolysis treated with human intravenous immunoglobulin.

AIM: Toxic epidermal necrolysis (TEN) is a severe drug reaction characterized by massive epidermal cell death. The authors of the current study and others have noted improved outcomes in TEN patients treated with human intravenous immunoglobulin (IVIG), purportedly due to its ability to inhibit the fas/fas-ligand (Fas-L) apoptotic pathway, but published case series evaluating TEN through the use of immunohistochemical antibody stains for Fas and Fas-L before and after IVIG treatment are lacking. The authors hypothesized that due to IVIG's ability to arrest the evolution of TEN, expression of Fas/Fas-L on keratinocytes would be decreased or absent following IVIG treatment. METHODS: Ten patients diagnosed with TEN underwent biopsies of their lesions prior to and five days after treatment with IVIG. Seven post-treatment biopsies were of sufficient quality to undergo evaluation. RESULTS: All ten pretreatment biopsies had Fas and Fas-L expression by immunohistochemistry, while six out of seven (85.7%) post-treatment biopsies failed to demonstrate Fas or Fas-L expression. One of seven post-treatment biopsies stained positive for Fas and Fas-L. CONCLUSION: This reduced immunohistochemical expression of apoptotic markers may represent IVIG inhibition of the pathogenic mechanism of TEN. Alternatively reduced Fas and Fas-L may be a feature of reepithelialization in TEN, or characteristic of rapidly proliferating epidermis.

Mucocutaneous pigmented macule as a result of zinc deposition.

BACKGROUND: Mucocutaneous depositions of various metals such as silver, lead, gold, arsenic, mercury, iron, and bismuth have been previously published. Heavy metal deposition typically occurs in the setting of either prolonged topical application to intact skin, topical application to eroded or ulcerated skin, as a result of either parenteral administration, or due to penetrating traumatic exposure. METHOD: We report a unique case of mucocutaneous pigmentation occurring in a snow skier after topical application of a zinc-containing sunblock. Formalin-fixed paraffin-embedded tissue was utilized for electron microscopy. RESULT: Backscatter electron imaging and energy dispersive spectroscopy revealed that the dominant metal present was zinc. CONCLUSIONS: Mucocutaneous deposition of metals is enhanced by damage to the surface epithelium. Metal-containing topical agents, although commonly used, may rarely result in a permanent pigmentary alteration. We believe similar cases of mucocutaneous deposition of zinc exist; however, as these may be currently misdiagnosed as amalgam tattoos, the true incidence of this disorder is presently undefined.

Seborrheic keratoses, solar lentigines, and lichenoid keratoses. Dermatoscopic features and correlation to histology and clinical signs.

Evaluation of the three benign lesions discussed here form the basis for dermoscopic evaluation of other pigmented skin lesions. The features of seborrheic keratosis, including [figure: see text] the various forms of fissures, comedo-like openings, and milia-like cysts, often allow easy interpretation of seborrheic keratosis; however, similar structures are commonly associated with melanocytic neoplasms, notably congenital nevi. Understanding solar lentigo and its dermoscopy features allows for the appreciation of pigment networks common in lentiginous melanocytic nevi and melanoma. The lichenoid keratosis is the model for lichenoid inflammation elsewhere, notably in halo nevi, regressing melanoma, and other melanocytic neoplasms with significant host inflammatory reactions.

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.

Analysis of thyroid transcription factor-1 and cytokeratin 20 separates merkel cell carcinoma from small cell carcinoma of lung.

Merkel cell carcinoma needs to be separated from small cell carcinoma metastatic from visceral sites to skin. Pulmonary small cell carcinoma is the most common primary site of small cell carcinoma. We evaluated the immunophenotypic characteristics of 21 Merkel cell carcinomas and 33 small cell carcinomas of lung using thyroid transcription factor-1 and cytokeratin 20. Thyroid transcription factor-1 was 100% specific for the diagnosis of small cell carcinoma of lung associated with a diagnostic sensitivity of 85%. Cytokeratin 20 was present in 95% of Merkel cell carcinomas; however, 33% of small cell carcinoma of lung were also positive. Both antibodies typically demonstrate diffuse and intense staining of their respective tumor cells. We conclude that thyroid transcription factor-1 is a sensitive and specific marker for small cell carcinomas of lung and that a combination of thyroid transcription factor-1 and cytokeratin 20 is indicated to assist in the differentiation of metastatic small cell carcinoma of lung from merkel cell carcinoma.

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.

Hansen's disease in a patient with a history of sarcoidosis.

We report a rare case of concomitant Hansen's disease (HD) and sarcoidosis. Reticulin staining may be a helpful diagnostic tool in establishing the diagnosis of sarcoidosis in skin lesions. The diagnosis of HD can be established despite negative polymerase chain reaction results for the detection of Mycobacterium leprae DNA. Finally, a well-established diagnosis of sarcoidosis does not preclude the development of another granulomatous disorder. Hence, when new lesions developed in a patient with sarcoidosis despite appropriate therapy, other concurrent diagnoses should be pursued.

The use of chlorambucil with prednisone in the treatment of pemphigus.

BACKGROUND: Chlorambucil is an alkylating agent that preferentially affects B cells over T cells and has been shown to be effective in the treatment of bullous pemphigoid. OBJECTIVE: Our purpose was to determine whether chlorambucil is effective in the treatment of pemphigus. METHODS: We retrospectively reviewed the medical records of 9 patients with pemphigus (7 with pemphigus vulgaris and 2 with pemphigus foliaceus) in whom therapy with other immunosuppressive regimens failed and who were subsequently treated with chlorambucil and prednisone. RESULTS: There was clinical improvement in 6 of 9 patients and a decrease in indirect immunofluoresent antibody titers in 3 of the 5 patients who had titers drawn before and after treatment with chlorambucil. Three of the 9 patients failed treatment with chlorambucil, as evidenced by lack of improvement of lesions. CONCLUSION: Chlorambucil may be a potential adjuvant therapeutic approach with steroid-sparing effects in patients with pemphigus who have failed treatment with other immunosuppressive regimens.

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.

Behavior of tissue-engineered skin: a comparison of a living skin equivalent, autograft, and occlusive dressing in human donor sites.

OBJECTIVE: To compare the behavior of a tissue-engineered living skin equivalent (LSE) with an autograft in acute donor site wounds. DESIGN: Paired-comparison, randomized control trial. SETTING: A university dermatology service. PATIENTS: Three donor sites were created on the anterior thigh of each of 20 patients requiring split-thickness skin grafts. INTERVENTION: For each patient, the donor sites were randomly assigned to be treated with meshed LSE, meshed autograft, or a polyurethane film (PUF) occlusive dressing. Blood and biopsy samples were taken for immunologic and histological studies. MAIN OUTCOME MEASURES: Toxic effects or clinically apparent rejection, humoral and cellular immune responses, clinical take, healing time, pain, and 1-month histological appearance. RESULTS: There was no toxic effect or clinically apparent rejection of LSE. Results of humoral and cellular studies were unchanged from baseline. The average time to healing for LSE with clinical take was 7.3 days (SD, +/- 0.8 days); for autograft, 7.6 days (SD, +/- 1.1 days); and for PUF, 9.5 days (SD, +/- 1.8 days). The difference between LSE or autograft and PUF was statistically significant at the .001 level. Pain was experienced by 1 patient, no patients, and 10 patients at the LSE, autograft, and PUF sites, respectively. Histologically, LSE had the thickest epidermis (P = .02), PUF had the greatest degree of fibrosis (P = .02), and autograft had the least degree of increased inflammation (P = .004) and vascularity (P = .01). CONCLUSIONS: In acute donor site wounds, LSE appeared to clinically take and to be a safe and usable form of tissue therapy.

Bednar tumor (pigmented dermatofibrosarcoma protuberans) occurring in a site of prior immunization: immunochemical findings and therapy.

Bednar tumor is a rare pigmented variant of dermatofibrosarcoma protuberans (DFSP). Because of its rarity, information is lacking regarding the optimal therapy and potential utility of immunohistochemistry in diagnosis. We report a case of Bednar tumor in which the diagnosis was aided by immunohistochemistry for CD34, an antigen known to be expressed in DFSP but not previously reported in Bednar tumor. Our case was also striking because it represents the first reported appearance of a Bednar tumor at a site of prior immunization, a phenomenon previously noted in some cases of DFSP. The patient was treated effectively with Mohs surgery and is without recurrence at 9 months.

Routine histologic examination for the diagnosis of onychomycosis: an evaluation of sensitivity and specificity.

Clinical differentiation of dermatophyte infection from dystrophic changes due to psoriasis may be challenging. Typically, potassium hydroxide (KOH) preparations, fungal culture, and occasionally, nail unit biopsy specimens are utilized to help differentiate between the two. These tests are often time-consuming and may yield false-negative results. Increasing regulation of the office laboratory has caused some physicians to forgo this testing, which was previously routine. We investigated the utility of routine histologic examination of nail clippings in differentiating onychomycosis from psoriatic onychodystrophy. Twenty-three distal nail clipping specimens (twelve specimens from patients with onychodystrophy of unknown cause and eleven control specimens from nails with known cause) were evaluated by routine histology and periodic acid-Schiff (PAS) staining. Of the dystrophic cases, four were demonstrated to be onychomycosis by the presence of hyphae on histologic evaluation and by culture, whereas only three of these cases yielded positive results on KOH examination. Eight cases of onychodystrophy were due to psoriasis. Yeast forms were detected on one case of psoriatic onychodystrophy that demonstrated yeast growth on culture. In our study, routine histologic examination with PAS staining was equal to culture and superior to KOH preparation in leading to the correct diagnosis of dermatophyte infection. In addition, the diagnosis of psoriasis of the nail plate was detected accurately by routine histologic examination. Routine histologic examination with PAS staining is a rapid, simple, and reliable test in the evaluation of onychodystrophy.

Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum.

BACKGROUND: Recombinant human interferon beta-1b has been recently approved for the treatment of multiple sclerosis. A significant proportion of patients treated with this medication experienced cutaneous reactions. OBJECTIVE: We describe the clinical and histologic features of cutaneous reactions to recombinant human interferon beta-1b. METHODS: Consecutive patients with cutaneous reactions to recombinant interferon beta-1b were evaluated clinically and by biopsy. RESULTS: Clinical lesions varied from subtle uninflamed sclerotic dermal plaques to erythematous plaques to cutaneous ulcers at injection sites. The nonsclerotic lesions were frequently painful. The firm plaques showed fibrosis histologically, whereas nonsclerotic inflammatory lesions demonstrated a consistent pattern of vascular thrombosis. Hematologic evaluation demonstrated platelet activation in most patients with inflammatory lesions, a feature also noted before interferon treatment in some patients. CONCLUSION: Therapy with recombinant interferon beta-1b is associated with a spectrum of cutaneous reactions and vascular thrombosis.

Dermatopathology via a still-image telemedicine system: diagnostic concordance with direct microscopy.

OBJECTIVE: To determine the concordance of dermatopathology diagnosis by still-image telemedicine technology and direct microscopy. MATERIALS AND METHODS: Skin specimens (N = 79) were examined by a dermatopathologist using a still-image phone system, and the diagnoses were compared with those made by the same dermatopathologist 1 year earlier by direct microscopy. The telemedical diagnoses were reached first without, and then with, patient histories. RESULTS: When the patient history was available, identical diagnoses were made in 66 of the 79 cases (84% concordance rate). Without patient history, the concordance rate was 80%. The diagnostic concordance rate for the diagnosis of benign nevocytic nevi, inflammatory diseases, and benign and malignant non-squamous cell carcinoma neoplasms was statistically significantly greater than the concordance rate for the diagnosis of squamous cell carcinoma and squamous cell carcinoma in situ (P = 0.005). CONCLUSIONS: The diagnostic concordance rate achieved by teledermatopathology using a still-image phone system fell short of the 99% intraobserver diagnostic concordance rate using direct microscopy.

Chromoblastomycosis.

Chromoblastomycosis is a chronic cutaneous infection due to several varieties of pigmented fungi. Diagnosis is straightforward and based on clinical and microscopic findings. Despite the protracted course of the disease, dissemination of the infection is rare. New insights into the pathophysiology may permit a closer appreciation of the clinical course. Treatment in advanced cases is difficult and frequently requires extensive surgery or lengthy therapy with physical or medical approaches.

Cloning of the 5' mRNA for the 230-kD bullous pemphigoid antigen by rapid amplification of cDNA ends.

The 230-kD bullous pemphigoid antigen (BPAG1), defined by autoantibodies in patient sera, is a hemidesmosomal plaque protein in the same gene family as the intracellular proteins desmoplakin I/II and plectin. We had previously isolated, from a lambda gt11 library, overlapping cDNA clones with 6921 bp of mRNA sequence for BPAG1. The coding sequence encoded by these clones included the 3' stop codon but not the 5' coding and non-coding region of the mRNA. To obtain these sequences we used the polymerase chain reaction (PCR) method called rapid amplification of cDNA ends (RACE). The PCR products were cloned into plasmids and sequenced. With five PCR primers we were able to obtain overlapping clones containing the 5' region of the mRNA. An upstream stop codon in frame with the rest of the coding sequence demonstrates that the full 5' coding sequence is obtained. Four different PCR products from two separate reactions had the same 5' end, suggesting that this 5' end is near, or at, the transcription start site. No alternatively spliced clones were found and no transmembrane site was predicted, confirming that BPAG1 is an intracellular hemidesmosomal plaque protein.