Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease.

BACKGROUND: Galli-Galli disease (GGD) is a rare genodermatosis. Its clinical presentation is identical to that of Dowling-Degos disease (DDD), but the presence of the histopathological feature of acantholysis in GGD is thought to distinguish the two disorders. Mutations in the keratin 5 gene (KRT5) have been identified in the majority of patients with DDD and in a small number of patients with GGD. OBJECTIVES: To provide further support for the hypothesis that GGD is merely a variant of DDD, and to examine whether acantholysis is genuinely rare in DDD or rather a common but under-reported histological feature of DDD. METHODS: We conducted the first systematic mutational investigation of patients with GGD and re-examined the histopathology of patients previously assigned a diagnosis of DDD. For the mutational investigation, KRT5 was sequenced in seven unrelated patients with clinically and histopathologically confirmed GGD. In addition, the histopathological findings of six patients with DDD were re-evaluated. RESULTS: The mutation c.418dupA was found in five patients with GGD. The typical histopathological features of GGD were identified in six patients who had previously been assigned a diagnosis of DDD. CONCLUSIONS: We found further evidence to suggest that GGD is indeed a variant of DDD and not a distinct disease entity. Two facts in particular support this conclusion: the same KRT5 mutation was found in patients with GGD and in patients with DDD, and acantholysis seems to be present in a large number of patients who had previously been assigned a diagnosis of DDD.

Rudimentary meningocele: remnant of a neural tube defect?

BACKGROUND: Rudimentary meningocele, a malformation in which meningothelial elements are present in the skin and subcutaneous tissue, has been described in the past under a variety of different terms and has also been referred to as cutaneous meningioma. There has been debate as to whether rudimentary meningocele is an atretic form of meningocele or results from growth of meningeal cells displaced along cutaneous nerves OBJECTIVE: We reviewed the clinical, histological, and immunohistochemical characteristics of rudimentary meningocele in an attempt to assess the most likely pathologic mechanism for it. DESIGN: Retrospective study. SETTING: University hospitals. PATIENTS: Thirteen children with rudimentary meningocele. MAIN OUTCOME MEASURES: Medical records were reviewed and histopathologic examination as well as immunohistochemistry studies were performed for each case. A panel of immunoperoxidase reagents (EMA, CD31, CD34, CD57, S-100, and CAM 5.2) was used to assess lineage and to confirm the meningothelial nature of these lesions. RESULTS: Recent evidence indicating a multisite closure of the neural tube in humans suggests that classic meningocele and rudimentary meningocele are on a continuous spectrum. CONCLUSION: Rudimentary meningocele seems to be a remnant of a neural tube defect in which abnormal attachment of the developing neural tube to skin (comparable to that in classic meningocele) could explain the presence of ectopic meningeal tissue. In the majority of cases, no underlying bony defect or communication to the meninges could be detected. However, in light of the probable pathogenesis, imaging studies to exclude any communication to the central nervous system should precede any invasive evaluation or intervention.

Granulomatous cheilitis and Borrelia burgdorferi: polymerase chain reaction and serologic studies in a retrospective case series of 12 patients.

BACKGROUND: Granulomatous cheilitis (GC) is a chronic granulomatous inflammation of the lips of unknown etiology, which may be associated with peripheral facial nerve paralysis and/or lingua plicata (Melkersson-Rosenthal syndrome [MRS]). Borrelia burgdorferi is a spirochete that causes Lyme borreliosis, a multisystemic infectious disease with frequent occurrence of facial nerve paralysis. An etiologic role of B burgdorferi in various granulomatous diseases has been suggested. The present study was performed to examine a possible causative role of B burgdorferi for GC/MRS by B burgdorferi-specific polymerase chain reaction analysis of biopsy specimens from affected lip tissue and determination of B burgdorferi IgG and IgM serum antibodies using enzyme-linked immunosorbent assay and immunoblot tests. OBSERVATIONS: We examined a retrospective case series of 12 patients with GC/MRS from a Lyme borreliosis endemic area (median duration of disease, 8 months [range, 3-348 months]). Borrelia burgdorferi-specific DNA could not be amplified by polymerase chain reaction in any of the 12 patients. One (13%) of 8 patients tested had a serum B burgdorferi IgG response on enzyme-linked immunosorbent assay, and 2 patients (25%) had an IgM response, but immunoblot testing yielded negative results in all 8 patients. CONCLUSION: The results of the present study do not indicate that B burgdorferi has an etiologic role in GC/MRS.

Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma.

The morphologic spectrum of large B-cell lymphoma is broad. Several unusual variants have been described such as lymphoma with myxoid stroma, sclerosing B-cell lymphoma, signet ring-cell lymphoma, and multilobated B-cell lymphoma among others. We report on five cases of cutaneous large B-cell lymphoma in which the neoplastic cells were spindle-shaped. In two cases, the clinical features fulfilled those of a primary cutaneous lymphoma; in the three other cases, the lymphoma most likely arose primarily in the skin, but incomplete clinical workups precluded definite categorization. The patients ranged in age from 30 to 89 years and presented with solitary lesions on the trunk or head. Histopathologic examination revealed nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm. Immunohistologic analysis revealed that both round or oval and spindled cells were positive for CD20 in all cases; in all cases tested, these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43, CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the rearrangement of the J(H) gene by polymerase chain reaction performed in one case showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise primarily in the skin in some cases. Recognition of this variant is necessary to avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.

Merkel cells and sclerosing epithelial neoplasms.

Merkel cells are normal constituents of the basal layer of the epidermis and the follicular epithelium. They have been identified in benign neoplasms with follicular germinative differentiation but seem to be absent in basal cell carcinomas (BCCs). Because sclerosing epithelial neoplasms are often sampled by small biopsies, any method that enables distinction among them would be welcome. We used immunohistochemical staining for cytokeratin 20 to assess the presence of Merkel cells in 14 cases of desmoplastic trichoepithelioma (DTE), 12 specimens of syringoma, 11 samples of morpheiform BCC, and 8 specimens of microcystic adnexal carcinoma (MAC). Merkel cells were found in association with all 14 specimens of DTE and in 1 of 11 cases of morpheiform BCC (p < 0.005) but in none of the specimens of syringoma or MAC. Our study supports previous findings that Merkel cells are seen in association with cutaneous neoplasms that are benign and of a follicular germinative origin. Although MAC may differentiate along follicular-sebaceous-apocrine lines, the absence of Merkel cells within it is consistent with its malignancy. The identification of Merkel cells in a sclerosing epithelial neoplasm of the skin points to DTE as the most likely diagnosis.

[The spectrum of cytotoxic lymphomas of the skin]. / Das Spektrum der zytotoxischen Lymphome der Haut.

Cytotoxic lymphomas are peripheral T- and natural killer-cell lymphomas with primary or secondary skin manifestations. They constitute a heterogeneous group of lymphoproliferative disease. They are characterized by expression of cytotoxic proteins and are frequently associated with an aggressive clinical course. A brief introduction to cytotoxic lymphocytes and proteins is followed by a detailed description of clinical, histological, immunohistochemical and genetic characteristics of cutaneous cytotoxic lymphomas.

The clinicopathologic spectrum of cytotoxic lymphomas of the skin.

Cytotoxic lymphomas of the skin comprise a spectrum of peripheral T cell and natural killer cell lymphomas with primary or secondary skin manifestations. They comprise a broad, heterogeneous group of lymphoproliferative disorders, and are characterized by expression of cytotoxic proteins (TIA-1, granzyme A and B, and perforin). These lymphomas often show an aggressive clinical course. In this article a detailed description of clinical, histopathologic, immunohistochemical, and molecular characteristics of cutaneous cytotoxic lymphomas follows a brief introduction on cytotoxic lymphocytes.

Histopathologic interobserver agreement on the diagnosis of melanocytic skin lesions with equivocal dermoscopic features: a pilot study.

AIMS AND BACKGROUND: Dermoscopy (dermatoscopy, skin surface microscopy, epiluminescence microscopy) has been increasingly employed in recent years for the preoperative detection of cutaneous melanoma, and dermatoscopic features of pigmented skin lesions have been previously defined using histopathology (HP) as the "key to the code". The aim of the present study was to evaluate the interobserver agreement on the HP diagnosis in a series of epiluminescence microscopy equivocal melanocytic skin lesions. STUDY DESIGN: Ten melanocytic skin lesions were selected on the basis of diagnostic disagreement of at least 2 out of 9 epiluminescence microscopy observers. The histologic specimens from the 10 lesions were examined by 9 HP observers. The agreement of the HP diagnoses was calculated by means of Fleiss' k statistics. RESULTS: The overall HP agreement was less than excellent (k = 0.5). When considering the prevailing epiluminescence microscopic and HP diagnoses, 2 cases were shown to be epiluminescence microscopy false-negative melanomas. Virtually no agreement was found among epiluminescence microscopy observers in 4 cases (40%) or among HP observers in 3 cases (30%). However, only one pigmented skin lesion remained unclassifiable on epiluminescence microscopy as well as HP. CONCLUSIONS: When at least 2 epiluminescence microscopy experts disagree in the evaluation of a given melanocytic skin lesion, even HP consultations may give equivocal results. The need to establish more reliable epiluminescence microscopic and HP criteria by performing an improved and meticulous clinicopathologic correlation, e.g. by using telecommunication via Internet, is emphasized.

Solitary skin lesions with histopathologic features of early mycosis fungoides.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually begins with cutaneous patches that evolve into plaques and tumors. A few recent reports describe a solitary variant of MF distinct from localized pagetoid reticulosis, a disease in which solitary verrucous lesions occur on acral skin. Solitary skin lesions with some of the histopathologic features of MF rarely occur during treatment with several drugs, especially antidepressants or antihistamines. We analyzed the clinicopathologic features of 20 patients with solitary skin lesions showing histopathologic features of patch- or early plaque-stage MF. Eight men and 12 women (mean age 50.6, range 23-82, median 49) had solitary, small erythematous patches or plaques located on the trunk (16 cases, 6 of them on the breast), upper extremities (3 cases), and inguinal region (1 case). Ten patients were treated with one or more drugs; only two of them received antidepressants or antihistamines. Histopathologic examination revealed in all cases a band-like infiltrate in the upper dermis, frequently with epidermotropism of solitary lymphocytes. Atypical lymphocytes were present in a minority of cases. Immunohistology showed a predominance of CD3+ T lymphocytes, in most cases admixed with clusters of CD20+ B-cells. Only a small proportion of the infiltrate was CD8+. Molecular analysis of the rearrangement of the T-cell receptor genes was performed in 16 cases using the polymerase chain reaction (PCR) technique and revealed a monoclonal band in 8 of them. After surgical excision, 2/14 patients had a recurrence near the surgical scar. In 18 patients with complete follow-up data, no evidence of "classic" MF could be observed after a mean follow-up of 31.9 months. Solitary skin lesions with the histopathologic features of MF can be considered as a distinct clinicopathologic entity, probably representing a solitary variant of mycosis fungoides.