Clinical and Serological Characterization of Orf-Induced Immunobullous Disease.

Importance: Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic. Objective: To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity. Design, Setting, and Participants: This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti-laminin 332 IgG were performed. Exposures: The disease course and clinical characteristics of orf-induced immunobullous disease were observed. Main Outcomes and Measures: Orf-induced immunobullous disease is primarily characterized by anti-laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease. Results: In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The α3, ß3, and γ2 chains were recognized in 2, 4, and 1 patient(s), respectively. Conclusions and Relevance: In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti-laminin 332 pemphigoid is proposed as distinct clinical entity.

Desmoplastic cellular neurothekeoma: Clinicopathological analysis of twelve cases.

BACKGROUND: Cellular neurothekeoma is a benign lesion most commonly found on the face and upper extremities in the first two decades of life. METHODS: Retrospective clinicopathologic review of 12 examples of cellular neurothekeoma typified by prominent stromal sclerosis, a distinctive variant that we refer to as desmoplastic cellular neurothekeoma. RESULTS: The mean age was 30 years (range, 3-55 years, 3 males, 9 females). The site was the head and neck in 3 cases, upper extremity in 4, lower extremity in 2, and trunk/abdomen in 3. All cases showed fascicles of slightly spindled and polygonal cells arrayed haphazardly in a prominent sclerotic background in the dermis and superficial subcutis. The cells displayed pale cytoplasm with indistinct membranes and vesicular nuclei with a single nucleolus. Lesional cells expressed NKI/C3, laminin, CD68, and CD10 and lacked expression of S-100 protein, EMA, and CD34. Clinical follow up was available on 10 cases with a mean duration of 24 months (range, 11-42 months) with no local recurrences or metastases. CONCLUSIONS: The immunohistochemical staining pattern, clinical findings, and benign nature are similar to "conventional" cellular neurothekeomas. The differential diagnosis includes desmoplastic melanocytic lesions, desmoplastic spindle cell carcinoma, dermatofibroma, "immature" scar, plexiform fibrohistiocytic tumor, perineurioma, and piloleiomyoma.

Orf-induced immunobullous disease: A distinct autoimmune blistering disorder.

BACKGROUND: Many complications have been reported after orf infection, including lymphadenopathy, secondary bacterial infection, and erythema multiforme. Rare associations with papulovesicular eruptions, including a bullous pemphigoid-like eruption, have also been described. OBJECTIVES: Our purpose was to clinically, histologically, and immunologically characterize two cases of orf-induced blistering disease, and to determine whether this condition represented a novel disease entity distinct from known immunobullous diseases. METHODS: Two patients were clinically described and skin biopsy specimens were collected for routine histology, direct immunofluorescence studies, and polymerase chain reaction analysis to detect orf viral DNA. Patients' sera were assessed for autoantibodies by indirect immunofluorescence studies using normal-appearing human salt-split skin, by Western blot analysis using keratinocyte extracts, dermal extracts, and recombinant type VII collagen, and immunoprecipitation studies of extracts from biosynthetically radiolabeled human keratinocytes. RESULTS: Two distinctive cases of severe, diffuse blistering eruptions after orf infection are described. In one patient, orf virus DNA was detected in the inciting orf lesion, but not in blistered skin, ruling out disseminated orf infection as a cause of the blisters. In both cases, histology revealed subepidermal blisters with mixed inflammatory cell infiltrates containing neutrophils and eosinophils, direct immunofluorescence microscopy studies demonstrated IgG and C3 deposited at the dermoepidermal junctions of perilesional skin, and indirect immunofluorescence studies demonstrated circulating antibasement membrane IgG that bound the dermal side of salt-split skin. Extensive immunoblot and immunoprecipitation studies failed to reveal a consistent, identifiable autoantigen. LIMITATIONS: We describe only two cases. The autoantigen recognized by circulating autoantibodies was not identified. CONCLUSIONS: Orf-induced immunobullous disease is a unique disease entity that is clinically and immunologically distinct from bullous pemphigoid, epidermolysis bullosa acquisita, and other known immunobullous conditions.

Clear-cell acanthoma versus acanthosis: a psoriasiform reaction pattern lacking tricholemmal differentiation.

Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely.

Cutaneous lupus erythematosus simulating squamous neoplasia: the clinicopathologic conundrum and histopathologic pitfalls.

BACKGROUND: The clinical distribution and character of cutaneous lupus erythematosus lesions can simulate squamous neoplasms, leading physicians to submit a shave biopsy specimen with a differential diagnosis of squamous neoplasm. OBJECTIVE: Our aim was to describe histologic features of interface dermatitis that cause difficulty in distinguishing between cutaneous lupus erythematosus and squamous neoplasia in shave biopsy specimens and to identify distinguishing criteria. METHODS: Twenty-six biopsy specimens from 10 patients initially diagnosed with squamous neoplasia that ultimately proved to be cutaneous lupus erythematosus were identified. Comparisons were made of these to 38 control biopsies of chronic cutaneous lupus erythematosus and 34 control biopsies of keratoses/carcinomas without lupus. All biopsies were scored (0 or 1: absent or present) with respect to 11 histologic criteria. RESULTS: The criteria of perifollicular inflammation, follicular plugging, vacuolar interface change, compact orthokeratosis, and acrosyringeal inflammation were significantly more common in the lupus cases than in the keratoses/carcinomas controls. The mean lupus case score was 6.88, lupus control score 6.55, and keratoses/carcinomas control score 5.08. LIMITATIONS: A limited number of patients were studied. Microscopic observations and assumptions with inherent subjectivity were used in establishing the histologic scores. CONCLUSION: Use of the criteria presented, although not absolute, should alert one to the possibility of lupus in an atypical squamous proliferation, especially in suspected squamous neoplasms that worsen or recur after therapy.

Cutaneous clear-cell granular cell tumors: the histologic description of an unusual variant.

BACKGROUND: Granular cell tumors (GCTs) are neoplasms showing nerve sheath differentiation that can arise in the skin but, to our knowledge, have not been associated with significant clear-cell morphology. METHODS: Two patients developed four separate GCTs with distinctive, diffuse clear-cell change, which completely camouflaged the primary differentiation. The morphology, histochemistry and immunohistochemistry of the lesions are described and are compared with the presence and extent of clear-cell change in 14 other cases of GCTs. RESULTS: The index cases were relatively broad proliferations with uniform diffuse clear-cell change and only minimal overlying epidermal hyperplasia. Prominent lymphoid nodules were present at the periphery. These clear-cell granular tumors were positive for S-100 protein, p75, CD68, NKI/C3 and neuron-specific enolase and were negative for epithelial mucin, periodic acid-Schiff, carcinoembryonic antigen, HMB-45, Melan-A, smooth muscle actin, Leu7, synaptophysin, CD34, factor XIIIa, epithelial membrane antigen and cytokeratin. Three of the fourteen comparison cases were found to have no clear-cell change, eight showed focal clear-cell change and three showed moderate clear-cell change. CONCLUSIONS: The distinctive morphology and the immunohistochemical results are discussed in the context of the differential diagnosis of clear-cell cutaneous tumors.

Self-healing juvenile cutaneous mucinosis: cases highlighting subcutaneous/fascial involvement.

BACKGROUND: Self-healing juvenile cutaneous mucinosis is a rare disease affecting young people characterized by transient cutaneous lesions and sometimes mild inflammatory symptoms. The deep dermal and subcutaneous features of this disorder have not yet been well described. OBJECTIVE: The purpose of our study was to present 3 cases of self-healing juvenile cutaneous mucinosis in which the histopathologic features caused diagnostic confusion between this disorder and proliferative fasciitis. METHODS: The study includes clinical and histologic findings of 3 patients, complemented by a literature review. RESULTS: The histologic descriptions of nodular lesions in self-healing juvenile cutaneous mucinosis reveal features of proliferative fasciitis, including a myxoid stroma and gangliocyte-like giant cells. LIMITATIONS: Self-healing juvenile cutaneous mucinosis is a rare condition and has not been frequently reported in medical literature. Our findings are based on the pathologic features of 3 patients. CONCLUSIONS: Our findings further elucidate the histologic features of self-healing juvenile cutaneous mucinosis and expand the differential diagnosis for entities in which gangliocyte-like giant cells are noted.

The dark side of photomicrographs in pathology reports: liability and practical concerns hidden from view.

The rapid evolution of digital imaging has facilitated the ability to include photomicrographs in pathology reports. Although these pictures may seem to be an informative accompaniment to the written report, there are many problems raised by the images, which are not generally recognized. These include lack of quality standards, selection of representative images, and liability implications, which are addressed by well-established legal precedent. For dermatologists there is no such thing as a casual interest in a photomicrograph on a report, for it acts to distribute a share of liability by obligating the clinician to interpret the image properly. The risk management ramifications of these unintended consequences should be strongly considered by clinicians who favor the receipt of photomicrographic images in their pathology reports.

Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma.

It is well documented that nevus cells can be found within the fibrous capsule and trabeculae of lymph nodes; however, it is less well known that nevus cells can also be found in the lymph node parenchyma. We report the findings in 13 cases of nevus cell aggregates located within the cortical and/or medullary parenchyma of lymph nodes. Seven of the 13 patients had a primary diagnosis of melanoma, three had no known malignancy, one had breast carcinoma, one had adnexal carcinoma of the skin, and one had squamous cell carcinoma of the tonsil. Of the seven patients with melanoma, four had axillary lymph node dissections and three had inguinal lymph node dissections. The patient with adnexal carcinoma had metastatic carcinoma in 14 of 20 lymph nodes that had been dissected; one of them also had intraparenchymal nevus cells. The patient with squamous cell carcinoma of the tonsil had an intraparenchymal nevus cell aggregate in one of the 21 dissected lymph nodes; all 21 were negative for carcinoma. Nests of intraparenchymal nevus cells ranged from clusters of only a few cells up to 2.1-mm aggregates. No mitotic figures, prominent nucleoli, or lymphatic-vascular invasion were detected in any of the melanocytic aggregates. The melanocytic cells of the nevus cell aggregates expressed S-100 protein and/or MART-1 but not gp100 protein (HMB-45). Less than 1% of the nevus cells expressed Ki-67. The purpose of this study was to draw attention to the finding of nevus cells in the parenchyma of lymph nodes and to alert pathologists to this as a potential diagnostic pitfall, especially in patients with concurrent melanoma or carcinoma. Awareness that nevus cells can be present in nodal parenchyma, analysis of their morphologic features (including comparison with any previous or existing melanoma or carcinoma), and immunophenotyping will help pathologists to establish the correct diagnosis in most instances.

Microtubule associated protein (MAP-2) expression defines the companion layer of the anagen hair follicle and an analogous zone in the nail unit.

BACKGROUND: Microtubule associated protein 2 (MAP-2) is one of a group of polypeptides that are an integral component of the microtubular cytoskeletal structure of the central and peripheral nervous system. During the course of another investigation that utilized immunohistochemistry, MAP-2 expression was observed in the hair follicle, almost exclusively in the innermost layer of the outer root sheath of the anagen follicle. This innermost layer, the so-called companion layer, has unique properties that clearly distinguish it from the rest of the outer root sheath. Among these are diminished glycogenation and an intimate association with the Henle's layer, which it directly apposes. Numerous intercellular connections exist between the companion layer and Henle's layer and, in fact, the companion layer accompanies Henle's layer during its vertical ascent in the follicle. Circumferentially oriented keratin filaments have also been demonstrated between the companion layer and Henle's layer, apparently providing structural support to the inner root sheath. Experimentally, disturbances in the keratin filaments of the companion layer in animals ultimately results in destruction of the hair follicle and an alopecia. METHODS: Immunohistochemical studies for MAP-2 were performed on 25 additional paraffin-embedded scalp specimens using standard techniques. Because of the parallels between the follicle and nail, MAP-2 expression in the nail unit was also investigated in three specimens. RESULTS: The presence of MAP-2 in the companion layer was confirmed in all cases. Intense MAP-2 expression in the companion layer begins at the B-fringe (the start of the keratogenous zone with cornification of the Henle's layer of the inner sheath) and extends to the level of the isthmus where the inner root sheath exfoliates. MAP-2 is also expressed in the upper layers of the nail matrix. CONCLUSION: The expression of MAP-2 almost exclusively in the companion layer is probably related to the unique cytoskeletal structure of this microanatomic layer. Since experimental evidence has shown that the cell cytoskeleton is important to the integrity of the hair follicle, it is probable that MAP-2 expression is also important and disturbances in its expression could play a role in the pathogenesis of some alopecias. MAP-2 may play a similar role in the nail matrix.