Factor XIIIa-positive dermal dendritic cells and HLA-DR expression in radial versus vertical growth-phase melanomas.

Fifty nevomelanocytic lesions, including 10 typical compound nevi and 20 radial and 20 vertical growth-phase melanomas, were evaluated for factor XIIIa and HLA-DR (LN3) expression within dermal dendritic cells (DDCs) or dermal dendrocytes to determine if DDCs proliferate and/or participate as possible antigen-presenting cells in the local tissue response to benign and malignant nevomelanocytic lesions. There was no statistical difference in factor XIIIa staining of DDCs between nevi and radial or vertical growth-phase melanomas, suggesting that DDCs do not significantly proliferate in nevomelanocytic lesions. However, studies to determine proliferation rate, apoptosis, and influences of local mediators on cell growth and/or recruitment were not done. HLA-DR staining by DDCs was significantly increased (p<0.001) in both melanoma groups when compared to compound nevi, but did not significantly differ between radial and vertical growth-phase melanomas. The intensity of HLA-DR expression appeared to correlate with the presence or absence of lymphocytic inflammation; HLA-DR intensity was judged greater in melanomas characterized by a brisk and infiltrative lymphocytic host response. We propose that DDCs may participate in the dermal immune response to invasive melanomas, probably as antigen-presenting cells to skin-associated lymphocytes.

Usefulness of the staged excision for lentigo maligna and lentigo maligna melanoma: the "square" procedure.

BACKGROUND: Management of lentigo maligna (LM) and lentigo maligna melanoma (LMM) may present problems because of the characteristic, yet unpredictable, subclinical peripheral and periadnexal extension of atypical junctional melanocytic hyperplasia beyond the visible margins. OBJECTIVE: We used paraffin-embedded (permanent) peripheral vertical section margin control in a staged fashion in the management of LM and LMM. METHODS: We used a modification of surgical excision in a staged fashion by means of a two-bladed knife with permanent peripheral vertical section margin control. RESULTS: This method is technically easy and results in complete histologic evaluation of the peripheral margins without compromising the measurement of tumor thickness of the primary melanoma. CONCLUSION: The use of the "square" procedure, a staged excision with permanent peripheral vertical section margin control, is useful in the management of LM and LMM.

The t(2;5)-associated p80 NPM/ALK fusion protein in nodal and cutaneous CD30+ lymphoproliferative disorders.

A high percentage of extracutaneous CD30+ anaplastic large cell lymphomas (nodal ALCL) carry a specific chromosomal translocation, t(2;5) (p23;q35), that results in abnormal expression of p80 NPM/ALK chimeric protein (p80). The protein p80 may be detected by immunohistochemistry using polyclonal (anti-p80) or monoclonal (ALK1) antibody directed against the ALK epitope. Although nodal ALCL, primary cutaneous ALCL, and lymphomatoid papulosis type A (lyp A) have similar histologic and immunohistochemical features, the expression of p80 in these cutaneous lesions has not been extensively studied. We immunostained tissues from 10 nodal ALCL, 8 primary cutaneous ALCL, 24 lyp A, and positive and negative controls using polyclonal rabbit anti-p80 and the avidin-biotin-peroxidase labeling method. Reactivity was determined by comparing staining intensity to positive controls [4 nodal ALCL with t(2;5)] and negative controls (21 non-ALCL lymphomas). Only cutaneous lesions staining positively with anti-p80 were further studied with the monoclonal antibody ALK1 and reverse transcription polymerase chain reaction (RT-PCR) for p80 messenger RNA. All positive controls (4/4), but none of the negative controls (0/21) nor lyp A (0/24), were immunoreactive for anti-p80. Sixty percent (6/10) of nodal ALCL and a single case (12%) of primary cutaneous ALCL were immunoreactive for anti-p80. In this exceptional cutaneous lesion, although we did not find NPM/ALK by RT-PCR, we detected strong expression of ALK using ALK1. We conclude that t(2;5) is rarely involved in the pathogenesis of cutaneous CD30+ lymphoproliferative disorders.

Recurrent trichofolliculoma of the upper eyelid margin.

We report a woman who had a recurrent trichofolliculoma on the upper eyelid margin. Only three cases of this benign tumor on the eyelid have been reported, and no recurrence in this location had been noted in the literature. The lesion, present for 6 years, had been excised twice previously (3 and 4 years before), recurred, and had been injected with a steroid preparation 2 years earlier. Lashes, both normal-looking and immature, arose from the center area of this lesion, and telangiectatic vessels were on its surface. Full-thickness wedge resection was used to excise the lesion completely. Complete primary excision of trichofolliculoma is important, and local steroid preparations should not be used.

Cicatricial alopecia.

Scarring alopecias are of diverse etiology and pathogenesis. They may be histologically classified as primary or secondary, depending on involvement of reticular dermis. The most important primary scarring alopecias include pseudopelade, lichen planopilaris, and diffuse scarring of the vertex in African-Americans. The most important secondary scarring alopecias include folliculitis decalvans and late-stage lupus erythematosus.

Cutaneous malignant melanotic neurocristic tumors arising in neurocristic hamartomas. A melanocytic tumor morphologically and biologically distinct from common melanoma.

Cutaneous neurocristic hamartomas (CNH) are pigmented lesions of neural crest origin that involve the skin and superficial soft tissue. They consist of a complex proliferation of nevomelanocytes, schwann cells, and pigmented dendritic and spindled cells. Malignancies can arise within the lesions, but few studies have dealt with this issue. We studied seven cases of CNH in which malignancy supervened. They included four congenital and three acquired lesions that involved the head and neck (five cases) or back (two cases) in patients aged from 11 to 67 (mean, 32) years. Malignant tumors developed 15 to 67 (mean, 32) years after identification of the pigmented lesion in the congenital CNH and after 1 to 6 (mean 3.5) years in the acquired CNH. The malignant tumors had a deep intradermal or subcutaneous origin and lacked a junctional component. Most were circumscribed, multinodular, melanin-containing tumors composed of bland, small, rounded to spindled cells, focally displaying a trabecular or nested growth pattern. Nuclear palisading and perivascular pseudorosettes were present in several tumors. In two examples, the neoplasm consisted predominantly of large pleomorphic epithelioid cells. Tumors contained immunoreactive S-100 protein (all of seven cases), a melanoma-associated antigen (HMB-45)( five of six cases, neuron-specific enolase (five of seven cases) and vimentin (six of six cases). The four patients with congenital lesions tended to have multiple recurrences and died of disease after 2 to 20 (mean, 9) years, three with metastases, one with direct invasion of the posterior fossa. The three patients with acquired lesions are alive after 1 to 5 years two with persistent disease. In contrast to common melanomas, these tumors have a propensity to recur as bulky nodules and to metastasize after many years or decades. Because these tumors exhibit melanocytic differentiation and arise in hamartomatous lesions composed of neural crest derivatives, we have designated them cutaneous malignant melanotic neurocristic tumors.

Fibroblastic rheumatism.

BACKGROUND: Fibroblastic rheumatism was first described in the French literature in 1980. Since that time, 11 other patients with this disorder have been identified in the literature, mostly from France. This is a unique syndrome characterized by the sudden onset of symmetric polyarthritis and cutaneous nodules ranging from 5 to 20 mm in diameter, with predilection for the upper and lower extremities. While the cutaneous findings resolve spontaneously after several months, permanent joint sequelae are common. OBSERVATIONS: We present the first two patients with fibroblastic rheumatism reported in the United States. The clinical features and histologic findings were identical to those of patients described in the European literature. CONCLUSIONS: Fibroblastic rheumatism is a relatively rare syndrome characterized by the association of multiple cutaneous nodules with polyarthritis. The clustering of cases in France may, in part, be attributable to increased recognition by clinicians owing to prevalence of reports in the European literature. Perhaps, as clinicians in the United States become familiar with this disorder, further cases will be diagnosed, and the pathogenesis of the disorder will be elucidated.

Periocular granuloma annulare, nodular type. Occurrence in late middle age.

We describe the two oldest individuals with nodular granuloma annulare (pseudorheumatoid nodules) in the ophthalmologic literature and propose a unified classification scheme that recognizes pseudorheumatoid nodules to be granuloma annulare, nodular type. All lesions in both cases revealed so-called necrobiotic granulomas, characterized by an acellular central area containing mucin (hyaluronic acid) surrounded by palisading histiocytes (macrophages), diagnostic of granuloma annulare. These features are identical to those reported in the ophthalmologic and older general pathology literature as pseudorheumatoid nodules and the contemporary general and dermatologic pathology literature as granuloma annulare. We believe the diagnosis of nodular granuloma annulare should be employed for necrobiotic lesions displaying distinctive clinicopathologic features to unite the ophthalmologic, general, and dermatologic pathology literature. Granuloma annulare, nodular type, must also be considered in the differential diagnosis of ocular and periocular lesions at any age.

Telogen effluvium. New concepts and review.

BACKGROUND: Telogen effluvium is the result of a perturbation of the hair cycle that is manifest by increased loss of normal club hairs. Although diverse causes for telogen effluvium have been proposed, this article suggests several diverse mechanisms for the first time. OBSERVATIONS: Five different functional types of telogen effluvia are proposed based on changes in different phases of the follicular cycle. These are immediate anagen release, delayed anagen release, short anagen syndrome, immediate telogen release, and delayed telogen release. Diverse causes are confirmed and drug-related telogen effluvia are reviewed. CONCLUSIONS: The five diverse mechanisms proposed for telogen effluvia are generally confirmed and supported by clinical findings.

Psammomatous melanotic schwannoma. A new cutaneous marker for Carney's complex.

BACKGROUND: Noncutaneous psammomatous melanotic schwannoma has recently been reported as an unusual component of Carney's complex (myxomas, spotty pigmentation, and endocrinopathy). The most common locations for this lesion include peripheral nerve roots and the gastrointestinal tract. OBSERVATIONS: A cutaneous psammomatous melanotic schwannoma is reported in a patient with known Carney's complex. This neoplasm was pseudoencapsulated, with epithelioid to spindle-shaped cells and no nuclear atypia. Immunostaining was positive for S100 protein and vimentin, as well for HMB-45 antibody. Electron microscopy showed melanosomes in cytoplasmic processes of cells that were ensheathed by layers of reduplicated basal lamina. CONCLUSIONS: Location in the superficial soft tissues is extremely unusual for psammomatous melanotic schwannomas. Recognition of this new cutaneous marker as a part of this complex may aid in identification of individuals at risk for cardiac myxomas. It is also important that this lesion is not mistaken for melanoma, given the strong HMB-45 positivity.

Oral submucosal dendrocytes: factor XIIIa+ and CD34+ dendritic cell populations in normal tissue and fibrovascular lesions.

Factor XIIIa+ and CD34+ dendritic cells, believed to be subsets of monocyte/macrophages, have been identified in dermis and in dermal tumors. The purpose of this study was to determine the presence and distribution of analogous cell types in oral submucosa and oral fibro-vascular lesions. Antibodies to XIIIa, CD34, S-100 protein, and macrophage antigen (MAC 387) were tested on formalin-fixed, paraffin-embedded tissue sections from normal mucosa, peripheral fibroma (PF), peripheral ossifying fibroma (POF), peripheral giant cell granuloma (PGCG), pyogenic granuloma (PG), lymphangioma (La), benign fibrous histiocytoma (BFH), idiopathic histiocytosis (IH), angiofibroma (Af) using an ABC immunoperoxidase technique. Numbers of positively stained cells were compared to unstained cells in the tumors. XIIIa positive submucosal dendrocytes (CD34-, S-100-, MAC 387-) were found in abundance in normal tissue in characteristic distributions: collagen-associated, vessel-associated, and lymphoid-associated. The percentage of XIIIa+ cells in the oral tumors was as follows: PF: 10-30%, POF: 5-10%, PGCG: 0-5%, PG: 5-20%, La: 0%, BFH: 5-25%, IH: 0%, and Af: 10-20%. CD34+ dendrocytes (XIIIa-, S-100-, MAC 387-) were few in number and were found in deeper submucosa, especially around skeletal muscle. Other than blood vascular endothelium, CD34+ cells were not generally seen in the oral tumors studied. It is concluded that two previously unrecognized dendrocyte populations reside in normal submucosa. XIIIa+ cells participate in the formation of some oral reactive and neoplastic lesions.

Varied clinical spectrum of necrobiotic xanthogranuloma.

Four cases are presented that illustrate a wide spectrum of ophthalmologic and systemic features of necrobiotic xanthogranuloma (NXG). Case 1 initially had signs of Cogan syndrome, and then developed chronic lymphocytic leukemia. Case 2, the first case of NXG to undergo autopsy, had progressive cicatricial lid retraction and corneal perforation. Case 3 had a more typical presentation of diplopia and blepharoptosis caused by orbital and periorbital infiltrative masses. Case 4 had nondeforming periocular skin lesions over a 6-year period. In all four cases, the diagnosis was made on the basis of characteristic histopathologic and laboratory findings. Although the cause of NXG is still obscure, in many cases it appears to be a forerunner of lymphoproliferative diseases.

Aggressive-growth basal cell carcinoma in young adults.

Aggressive-growth basal cell carcinoma (AG-BCC) defines a group of basal cell cancers that are histologically and clinically aggressive. This group includes morpheaform, infiltrating, and recurrent BCCs. Because of the clinical observation that the incidence of AG-BCC may be increased in patients under 35 years of age, compared with those older, we performed a retrospective study. We reviewed the pathologic findings of 3381 patients diagnosed with BCC, including 102 patients with BCC referred for Mohs surgery to determine whether AG-BCC occurs with increased frequency in patients younger than than 35 years of age. Among patients under 35 years of age, 38% of women had AG-BCC compared with 9% of women in the older age group. Similarly, 25% of men under 35 years of age had AG-BCC compared with 11% among men in the older age group. Aggressive-growth BCC is more frequently noted in patients under 35 years of age than in those older. Failure to diagnose this type of BCC, which may be clinically subtle, may lead to incomplete or inadequate treatment. Because of the tendency of these tumors to recur, greater long-term morbidity may result.

Cutaneous lymphadenoma.

Thirteen cases of a unique cutaneous tumor are presented. The lesions presented as single, nondescript, skin-color nodules. Eleven were located on the head and two were on the legs. The male/female ratio was 8:5. The age at diagnosis ranged between 21 and 55 years (mean: 39). The duration of the lesions was from several months to more than 20 years. All tumors were excised and did not recur. The tumors typically presented as well-circumscribed nodules with scant or no epidermal connections. (One example, however, had a plate-like configuration amply connected with the basal layers of the epidermis.) The proliferation consisted of multiple, rounded lobules of basaloid cells with some degree of peripheral palisading, immersed in a dense, fibrous stroma. There was an intense infiltrate of small lymphocytes within the lobules, with some spillage into the stroma. No clear adnexal differentiation was noted except for rare isolated cells showing apparent sebaceous differentiation within the tumor lobules. Areas of central keratinization were also present. Numerous cells with ample amphophilic cytoplasm, large vesicular nuclei, and prominent nucleoli were also seen. Immunohistochemistry confirmed the presence of keratin within tumor cells. Common leukocytic antigen highlighted the intense intralobular lymphocytic component. Vimentin not only highlighted the stromal fibroblastic component, but also stained scattered intralobular cells. Epithelial membrane antigen was positive within some of the large intraepithelial cells. S-100 protein was extensively positive within dendritic intralobular and stromal cells. Lymphocytic markers demonstrated a polyclonal B and T population. This unique tumor appears to represent a form of adnexal neoplasm with basaloid features, possibly immature pilosebaceous differentiation.

Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin.

We performed a 22-month trial of topical tretinoin (retinoic acid) in the treatment of photoaging. Thirty patients participated in a 4-month, randomized, blinded, vehicle-controlled study that has been reported previously; 21 patients continued tretinoin therapy on an open-label basis, participating in the study for a total of 10 months, and 16 patients continued for 22 months. During the open-label study, the statistically significant improvement that had occurred in fine and coarse wrinkling and skin texture during our original study was sustained, despite reductions in dose or frequency of application of tretinoin. The number of discrete lentigines decreased by 71% compared with the number before therapy. Histologic findings included a statistically significant thickening of the epidermis. Side effects were limited to a cutaneous retinoid reaction that diminished as therapy proceeded.