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Eccrine squamous syringometaplasia (ESS) has been associated with several conditions including morphea, linear scleroderma, and burns. It is yet to be reported in lichen sclerosus et atrophicus (LSA). We describe a bullous LSA plaque on the forearm of a woman with pre-existing genital LSA and vitiligo. Besides the histopathological findings of bullous LSA, numerous small irregular squamoid structures were present in the mid and upper dermis always above the normal eccrine glands. The histopathology, periodic acid-Schiff stain, and positive immunostains for P63, low molecular weight keratins 818, epithelial membrane antigen, and carcinoembryonic antigen supported the diagnosis of ESS. The pathogenesis of ESS in LSA may be related to ischemia, inflammation, and fibrosis.

BACKGROUND Periodic acid-Schiff (PAS) staining of nail clippings is an adjunct diagnostic tool for onychomycosis. OBJECTIVE To detect histopathological findings as clues to the presence of PAS-positive (+) fungal elements in nail clippings. METHODS Four hundred sixteen consecutive nail clippings suspected of onychomycosis were stained with hematoxylin and eosin, and with PAS stains. All cases were studied histopathologically. The clinical files of the cases with neutrophils were reviewed. RESULTS PAS+ staining for fungi were demonstrated in 159 (38%) of the nail clippings. Neutrophils, parakeratosis, plasma globules, and bacteria were observed in 43 (27%), 108 (67%), 80 (50%), and 80 (50%) of the PAS+ cases, respectively, and in 17 (6%), 109 (41%), 84 (32%) and 140 (54%) of the PAS- cases, respectively (P < 0.01). Neutrophils showed by far the highest specificity (93%), although with low sensitivity (27%) for the presence of PAS+ fungi. Among the 43 PAS+ and 17 PAS- specimens with neutrophils, only 1 (2.3%) and 3 (17%) had overt psoriasis, respectively. CONCLUSION Neutrophils in nail clippings may serve as a clue for onychomycosis. PAS staining with neutrophils is not necessarily associated with psoriasis.

Neonatal autoimmune subepidermal blistering disease is rare. Mucosal involvement is more common in neonatal linear immunoglobulin A (IgA) bullous dermatosis. We describe a neonate with subepidermal cutaneous blistering disease with severe laryngeal and esophageal involvement leading to acute respiratory distress. Histopathology demonstrated a subepidermal blister with neutrophils and eosinophils at the dermal base. Collagen IV was detected at the dermal floor, and direct immunofluorescence showed linear IgG, IgA, and C3 deposits at the basement membrane zone. The patient demonstrated markedly increased serum levels of anti-BP180 NC16A and anti-BP230 IgG antibodies (Abs) but failed to show anti-LAD-1 IgA Abs. His healthy mother showed serum anti-LAD-1 IgA Abs but did not show anti-BP180 and anti-BP230 Abs. The neonate responded promptly to systemic corticosteroid therapy. A review of the literature detected 11 cases of neonatal subepidermal blistering disease with linear IgA deposits. Nine of these cases demonstrated coexisting linear IgG deposits, often with C3. Respiratory compromise was present in most of the cases. Neutrophils and eosinophils were commonly present in the inflammatory cell infiltrates. Besides our case, 2 cases of neonatal IgG/IgA subepidermal blistering disease with esophageal involvement were previously described. IgA Abs were present in the sera of both cases. Anti-LAD-1 IgA Abs were detected in the mother's serum of our case alone, but IgA Abs do not cross the placenta. Our case was consistent with neonatal IgG/IgA pemphigoid. Neonatal IgG/IgA subepidermal blistering disease may be associated with severe laryngeal and esophageal involvement leading to respiratory compromise. Expedited diagnosis and prompt treatment are warranted.

The development of T-cell lymphomas, granulomatous reactions, and autoimmunity has been observed in immunodeficiency due to milder forms of recombination activating gene (RAG) deficiency. A few cases of cutaneous clonal papulonodular CD8 lymphocytic infiltrates and cutaneous CD8 granulomatous T-cell lymphoma have been described in association with common variable immunodeficiency, and with X-linked agammaglobulinemia. We describe a 15-year-old girl with several autoimmune disorders and recurrent infections that presented with several nodules on her cheek. Histopathological studies demonstrate histological, immunohistochemical, and molecular findings compatible with a primary cutaneous clonal CD8 T-cell lymphoproliferative disorder. Vacuolar interface changes were also seen in the involved skin, reminiscent of cutaneous lupus erythematosus. Molecular genetic analysis revealed a germline novel homozygous missense mutation in RAG1 (T1003>C). The parents were heterozygous carriers. The facial cutaneous lesions recurred despite local radiation therapy. Because of recurrent life-threatening systemic infections, allogeneic bone marrow transplantation was performed. The pathogenesis of this primary cutaneous clonal CD8 T-cell lymphoproliferative disorder may have been related to a chronic stimulation of autoreactive T cells in the involved skin paired with reduced RAG1 activity.

Pigmented contact dermatitis (PCD) is a noneczematous variant of allergic contact dermatitis, and benzyl salicylate is one of its causes. This type of PCD shows nonlichenoid interface dermatitis with pigment incontinence. We aimed to characterize the earliest histopathological changes of this reaction. A 51-year-old man presented with persistent facial eruption composed of hyperpigmented and hypopigmented macules due to exposure to benzyl salicylate present in his aftershave. The biopsies obtained from hyperpigmented and hypopigmented macules, and from the positive patch test site to benzyl salicylate, showed a nonlichenoid focal vacuolar interface dermatitis with mononuclear cells in the papillary dermis and around the pilosebaceous units, along with melanophages. A MART-1 immunostain showed intact melanocytes in all 3 biopsies. A Fontana-Masson stain demonstrated intact melanin in the basal cell layer of a facial hyperpigmented macule and the patch test site, but melanin was reduced in the biopsy taken from a hypopigmented facial macule. There were more epidermal and dermal CD1a+ Langerhans cells in the patch test biopsy than in the other 2 biopsies. Most of the mononuclear cells were CD3+. The CD4+ to CD8+ ratio was approximately 1:1 in the facial macules; yet, CD4+ cells outnumbered CD8+ cells in the patch test biopsy. There were a few TIA-1+ cells in all 3 biopsies. In conclusion, the earliest histopathological and immunophenotypical events in PCD due to benzyl salicylate are similar to those of longer-standing lesions, i.e., a nonlichenoid focal interface dermatitis involving the epidermis and pilosebaceous unit, along with dermal melanophages.

Background Several cases of folliculotropic mycosis fungoides, associated with immunosuppressive therapy, including calcineurin inhibitors, have been reported in solid organ transplant patients. We have encountered 3 patients on immunosuppressive therapy who developed follicular eruptions with folliculocentric infiltrates of nonatypical lymphocytes. Objective To characterize these follicular eruptions and review the literature. Methods Three patients, aged 7-15 years, who were treated with systemic immunosuppressive therapy developed follicular eruptions characterized histopathologically by folliculocentric lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly for T-cell receptor (TCR) gene rearrangement. Results All 3 cases were characterized histopathologically by folliculocentric infiltrates of nonatypical CD3 T lymphocytes with variable follicular exocytosis. Two cases also showed follicular mucinosis. Marked reduction in CD7 staining, and marked predominance of CD4 cells over CD8 cells was observed in all 3 cases. The TCR gene rearrangement studies were monoclonal in 2 cases. Oral calcineurin inhibitors (2 cyclosporine A and 1 tacrolimus) were part of the therapeutic regimen in all 3 patients. Their cessation along with local corticosteroid creams in 2 patients, and phototherapy with oral acitretin in one patient, was associated with complete clinical remission. Conclusions Patients undergoing systemic immunosuppressive therapy that includes calcineurin inhibitors might develop follicular eruption with some immunophenotypical variations and a monoclonal TCR gene rearrangement but lack sufficient cytomorphological features of folliculotropic mycosis fungoides. Altering the immunosuppressive agent including calcineurin inhibitors may result in regression of the eruptions.

Background Several cases of pityriasis lichenoides (PL) have been reported to evolve into mycosis fungoides (MF). Objective To elucidate clues to this progression. Methods Fifty-eight patients with PL between 2000 and 2013 (follow-up: 3-16 years, average: 8.3). Results A total of 3 (5.2%) of the 58 patients with PL developed MF after 3-11 years of prolonged clinical course. Papules and small plaques characterized PLs, and patches and larger plaques subsequent MFs. A total of 35 of 41 (85%) followed up non-MF associated patients with PL reported lasting complete remissions. Histopathologically, apoptotic keratinocytes disappeared mostly or completely in subsequent MFs. The presence of epidermotropism, folliculotropism, and epidermal lymphocytic nuclear atypia in PLs was not predictive of MF. CD8 cells were the dominant intraepidermal lymphocytes in the 3 PLs but remained so in only 1 subsequent MF. CD7 lymphocytes decreased substantially in 2 MFs, and lymphocytic nuclear atypia increased markedly in 1. T-cell receptor gene rearrangement studies demonstrated clonal populations in 1 of 2 studied PLs and in all 3 subsequent MFs. Conclusions A few PLs may evolve into MF. Prolonged clinical course, appearance of patches and larger plaques, markedly increased lymphocytic nuclear atypia, marked diminution of apoptotic keratinocytes and CD7 and CD8 lymphocytes, and clonal T-cell receptor gene rearrangement may serve as clues.

Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny.

Background Histopathology plays an important role in the diagnosis of cutaneous leishmaniasis (CL) but Leishman-Donovan (LD) bodies may not always be discernible. Recently, anti-CD1a antibody (Ab), clone MTB1, was found to decorate LD bodies immunohistochemically. Objective Can histopathology without discernible LD bodies be used to diagnose CL, and can immunohistochemistry using anti-CD1a Ab, clone MTB1, detect LD bodies in these cases. Methods Suspected CL lesions were studied histopathologically and immunohistochemically, and the patients' clinical files were reviewed. Results Of the 196 patients with suspected CL, direct smear demonstrated LD bodies in 50 (25.5%). Of the remaining 146 patients, 118 underwent biopsy. In 56 (47.5%) patients, the hematoxylin-eosin-stained sections revealed LD bodies. In 47 (39.8%) patients, LD bodies were not discerned but the histopathology demonstrated histiocytic infiltrates with varying numbers of plasma cells along with other inflammatory cells, and negative Ziehl-Neelsen and periodic acid-Schiff stains. This pattern was termed "histopathology consistent with leishmaniasis." The history, clinical findings, and response to anti-leishmania therapy supported the diagnosis of CL in all of them, and immunostains for CD1a, clone MTB1, detected LD bodies in 11 (23.4%) of these 47 patients. Conclusions "Histopathology consistent with CL" along with appropriate clinical findings supports the diagnosis of CL in an endemic area, and immunostains with CD1a Ab, clone MTB1, may help in the minority of the cases.

Demodex is a saprophytic mite in humans commonly present in the pilosebaceous units, which has been implicated as a pathogen in several skin conditions. The clinical presentation and histopathology of Demodex folliculitis of the scalp have been described in only a few case reports. This study was performed to further elucidate the clinicopathological features of this entity. We have studied 333 consecutively submitted scalp biopsies performed for hair loss and alopecia. All specimens were completely step-sectioned. Biopsies with Demodex mites were further studied histopathologically, and the patients' clinical files were reviewed. There were 17 biopsies (5.1%) with Demodex in at least 1 pilosebaceous unit. Based on the clinical presentation, histopathology, and response to therapy, Demodex was considered to be nonpathogenic in 13 cases. The remaining 4 cases were characterized by hair loss, scalp erythema, scales, and pustules. There were 2 or more pilosebaceous units with Demodex along mononuclear and/or neutrophilic infiltrates around and in the involved follicles and occasionally granulomas. All 4 cases responded completely to metronidazole therapy. In conclusion, Demodex is infrequently found in scalp biopsies for hair loss and alopecia, and, in most cases, it does not seem to be pathogenic. Occasionally, however, it is associated with folliculitis characterized by hair loss, erythema, scales, and pustules clinically; neutrophilic and/or mononuclear-cell folliculitis with occasional granulomas histopathologically; and a prompt response to anti-Demodex therapy.

T-cell receptor gene rearrangement studies are considered to be an adjunct to the histopathological diagnosis of mycosis fungoides (MF). Fluorophore-coupled primers in polymerase chain reactions followed by fragment analysis with a capillary electrophoresis device (GeneScan analysis) have been recently advocated and widely used. This study was performed to assess T-cell receptor γ-gene rearrangement GeneScan as an adjunct to the histopathological diagnosis of MF. We studied 163 cases. The rates of clonality using this technique were found to be 22/37 (59.5%) in early patch MF, 30/46 (65.2%) in more advanced stages, 13/34 (38.2%) in inconclusive cases, and 10/46 (21.7%) in benign inflammatory dermatoses. Our results support the histopathological criteria for the diagnosis of early patch MF, because of the close rates of clonality obtained in early patch MF with subtle histopathological findings, and in the more advanced subtypes of MF with more overt and specific histopathological criteria.

Bone involvement has been described in tumors with melanocytic differentiation such as melanotic neuroectodermal tumor of infancy, and very rarely in cellular blue nevi and neurocristic cutaneous hamartoma. We present an unusual case of facial congenital melanocytic tumor that involved the underlying bones and maxillary sinus and led to unilateral blindness. A newborn with a large red bluish patch with peripheral brown and black macules overlying marked swelling on the left side of his face was presented. The tumor was shown by magnetic resonance imaging, scintigraphy, and histopathology to invade the underlying bones and maxillary sinus and to compress the left eyeball resulting in blindness. Histopathology, immunohistochemistry, morphometric computerized microscopy, molecular genetic mutation analysis, and fluorescent in situ hybridization studies were more congruent with a melanocytic nevus. An 8.5-year follow-up was uneventful, with spontaneous partial shrinkage of the tumor.

The relationship between acrokeratosis verruciformis (AKV) of Hopf and Darier disease (DD) has been debated for several decades. Both diseases are now thought to result from mutations in the same gene, that is, the ATP2A2 gene encoding the sarco (endo) plasmic reticulum Ca ATPase2 pump (SERCA2), although their histopathological features are different. We sought to detect possible overlapping histopathological features between AKV and DD. Fourteen members of a family affected by AKV were analyzed for the underlying molecular genetic derangement, and 3 cases were studied histopathologically using multiple step sections. A heterozygous P602L mutation in ATP2A2 was identified as the underlying cause in this family. This mutation and a heterozygous A698V were previously described in AKV. Both mutations were not among the 162 mutations in ATP2A2, which were reported to date in DD. The histopathological study demonstrated in several consecutive step sections of 2 of the 3 studied cases, foci of small suprabasal clefts with acantholytic keratinocytes, some of which were mildly dyskeratotic. These focal features were reminiscent of the basic histopathological characteristics of DD. These shared histopathological features of AKV with DD suggest that AKV and DD are allelic disorders with variable expression of the same disease, although identical mutations in ATP2A2 in AKV and DD were not reported to date.

The diagnosis of onychomycosis, using direct microscopy and fungal cultures, is often negative despite the presence of disease. Periodic acid-Schiff (PAS) staining of nail clippings, using histopathological processing, may be positive in these cases. It is not always clear, however, whether the fungal elements detected by PAS staining are pathogenic fungi or some are saprophytes. We aimed to study the efficacy of histopathological PAS staining of nail clippings as a second-line diagnostic tool in onychomycosis. The study included 100 consecutive cases in which direct microscopy and fungal cultures from suspected onychomycosis were negative on one occasion or more. The obtained nail clippings were processed for routine histology, stained with hematoxylin and eosin and PAS, and examined microscopically. Of the 100 cases, 38 (38%) showed positive fungal elements. As a result, 9 patients had sought and received oral antifungal therapy and all achieved complete clinical cure. The histological examination also revealed parakeratosis and globules of plasma, which were statistically significantly more common in the fungal infected nail samples. This may indicate an ongoing inflammatory process associated with onychomycosis. Neutrophils and bacteria were not statistically and significantly more common in the fungal infected nails. We conclude that as a second-line diagnostic tool, PAS stain of nail clippings increases markedly the diagnostic yield of onychomycosis and, consequently, the outcome of therapy.

H syndrome (OMIM 612391) is a recently described autosomal recessive genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin and systemic manifestations including hepatosplenomegaly, cardiac anomalies, hearing loss, hypogonadism, low height, hypertriglyceridemia, hallux valgus, and flexion contractures. H syndrome results from mutations in the SLC29A3 gene, which encodes the human equilibrative nucleoside transporter hENT3. The cutaneous histopathology is characterized by a striking mononuclear cell infiltrate in the dermis consisting of CD68+ monocyte-derived cells and CD34+ and factor XIIIa+ dendrocytes. We describe a case of H syndrome in which the infiltrating mononuclear cells were CD68+, CD163+, S-100+, and CD1a-, thus simulating the immunophenotype observed in Rosai-Dorfman disease (RDD). The immunostaining for CD21, fascin, and CD34 were negative, and there were also many factor XIIIa+ dendrocytes interspersed within the dense mononuclear cell infiltrate. Recent findings of biallelic mutations in SLC29A3 in 2 families reported to have familial RDD and in a kindred with Faisalabad histiocytosis (OMIM 602782), which is an autosomal inherited form of histiocytosis with similarities to RDD, may explain the RDD-like immunophenotype in our H syndrome case.

Background The classical histopathological findings in the epidermis of pityriasis rubra pilaris (PRP) do not include acantholysis; however, acantholysis was described in several case reports and a few series of PRP with variable frequencies. We sought to establish the incidence of acantholysis in biopsies from consecutively referred PRP cases using multiple-step sections and clinicopathologic correlations. Methods Twenty-three biopsies from 12 consecutively referred patients with classical (type 1) PRP were studied histopathologically. Each specimen was completely step sectioned. The clinical files of the patients were also reviewed. Results Small foci of acantholysis were observed in some of the step sections of 5 of 23 (22%) biopsies obtained from 4 patients. Three biopsies showed suprabasal acantholysis, 1 of which also demonstrated mild dyskeratosis and 2 showed midepidermal acantholytic foci as well. The remaining 2 biopsies demonstrated midepidermal and subcorneal acantholysis, respectively. Small erosions were described in the physical examination of 2 of the 4 (50%) patients with acantholysis and in 1 of the 8 (12.5%) patients without acantholysis. Limitations The number of cases. Conclusions Small foci of acantholysis may be found in the minority of PRP biopsies, and it may be related to small erosions clinically in some patients.

Pleomorphic small/medium-sized cutaneous T-cell lymphoma is a recently recognized rare type of cutaneous T-cell lymphoma which is clinicopathologically different from mycosis fungoides and Sezary syndrome. By definition the phenotype of the neoplastic lymphocytes in pleomorphic small/medium-sized cutaneous CD3CD4CD8 but CD8 pleomorphic small/medium sized cutaneous T-cell lymphoma cases have been occasionally described. We describe a 55-year-old female with a pruritic erythematous nodule on the lateral aspect of her right foot present for 1.5 years. Histology revealed a nonepidermotropic lichenoid infiltrate in the papillary dermis and a patchy infiltrate in the mid and lower dermis composed of small to medium-sized pleomorphic lymphocytes. The immunophenotype of these lymphocytes was CD3CD4CD8TIA-1. Staining for CD20, CD30, CD56, TdT, and LMP1 were negative, and the Ki-67 proliferation index was 5% to 10%. Gene rearrangement studies demonstrated a T-cell clone. The laboratory and imaging workup did not reveal extracutaneous involvement. The lesion was treated by local irradiation but a follow-up biopsy demonstrated only partial remission. Consequently, the lesion was treated by surgical excision.

Alemtuzumab is a humanized mouse antibody targeting the CD52 cell surface, which has been effective in patients with advanced stage mycosis fungoides (MF) including erythrodermic MF and Sezary syndrome. There are a few descriptions of large cell transformation after its administration. A young patient with an acute onset of Sezary syndrome treated initially unsuccessfully with fludarabine and cyclophosphamide and later on successfully with alemtuzumab has been described. Three weeks after the beginning of therapy, however, she developed transformed T-cell lymphoma indistinguishable from CD30 anaplastic large-cell lymphoma. After bone marrow transplantation, the transformed CD30 cutaneous T-cell lymphoma recurred as a transformed CD30 plaque MF. All 3 types of lesions showed the same T-cell receptor clonal gene rearrangement, which supports the notion that Sezary syndrome, CD30 anaplastic large-cell lymphoma, and MF are interrelated.

A cutaneous eruption simulating insect bites has been repeatedly described in association with chronic lymphocytic leukemia (CLL). It was only rarely described with mantle cell lymphoma (MCL). Our study was performed to elucidate the clinical, histologic, immunopathological, and molecular characteristics of insect bite like reaction (IBLR) associated with MCL. The clinical presentation and histologic findings in 3 IBLR cases associated with MCL were found to be similar to 3 IBLR cases associated with CLL. The eruptions consisted of itchy erythematous papules, nodules, plaques, and vesicles. Non-vesicular lesions were characterized histologically by normal or mildly spongiotic epidermis. Vesicular lesions were characterized by marked spongiosis and intraepidermal spongiotic vesicles containing eosinophils, or marked subepidermal edema occasionally leading to a dermoepidermal separation. Most of the lesions were characterized by superficial and mid dermal to deep perivascular and interstitial, and occasionally periadnexal, inflammatory-cell infiltrate consisting of mononuclear cells and eosinophils. The densities of the infiltrates varied and the inflammatory-cell infiltrate extended often into the fat lobules. Neutrophils and nuclear dust were found more frequently and abundantly in the IBLR lesions associated with MCL. Immunophenotyping, direct immunofluorescence (DIF) tests, and IgH gene rearrangement studies were performed in the lesions associated with MCL only. The majority of the infiltrating lymphocytes were CD3+, CD5+ and CD43+, more CD4+ than CD8+, and only a small minority was CD20+. The cells did not stain for bcl-1 protein and CD30, and with no evidence of clonality. The DIF test result was negative. The IBLR eruption associated with MCL resembles clinically and histologically IBLR associated with CLL. The eruption seems to be reactive rather than neoplastic, because there is no evidence of MCL involvement in the skin lesions.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by progressive, tumor-like calcifications in the dermis and subcutaneous tissues. The disease is associated with primary hyperphosphatemia due to increased renal tubular reabsorption of phosphate. We recently identified mutations in GALNT3 as the proximal cause of this metabolic disorder. GALNT3 encodes the glycosyltransferase UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (ppGalNAc-T3), which initiates mucin-type O-glycosylation and thus takes part in posttranslational modification and formation of mucin-type glycoproteins. A number of studies have previously described the histopathological and ultrastructural features of lesional skin in HFTC, but little is currently known about the morphology of the normal-appearing non-lesional skin. We obtained biopsies of uninvolved skin from two HFTC patients carrying a known splice site mutation in GALNT3. Light and electron microscopic examination of a biopsy of one of the two patients did not reveal abnormal findings in the epidermis or dermis. However, immunohistochemical studies of frozen skin sections of biopsies of the two patients using monoclonal antibodies directed against three ppGalNac isoforms revealed the complete absence of immunostaining for ppGalNAc-T3 while the staining pattern for ppGalNAc-T2 and -T6 was identical in skin biopsies obtained from HFTC patients and healthy control individuals. Our data provide for the first time evidence for ppGalNAc-T3 deficiency in the skin of HFTC patients and suggest that immunostaining of skin biopsy samples for ppGal-Nac-T3 might be a useful tool for the diagnosis of HFTC.

Multiple trichoepitheliomas (TEs), especially in the familial setting, have been associated with germline heterozygous mutations in the CYLD gene. Heterozygous germline CYLD mutations and loss of heterozygosity of the CYLD gene in the TE tumor cells have been recently demonstrated in some of the multiple TE cases irrespective of a family history. The histopathological differential diagnosis of TE from basal cell carcinoma may be difficult especially in cases with multiple TEs. Immunohistochemical markers may be used, although some with conflicting results. We describe a 35-year-old woman with multiple facial TEs, in whom the molecular genetic analysis revealed a novel heterozygous c.1843delT mutation in the CYLD gene. This frameshift mutation was also present in a heterozygous state in the TE tumor cells. The demonstration of a novel CYLD mutation was used as an adjunct to the histopathological diagnosis in this case.

Electron microscopic examination still is the gold standard for classifying epidermolysis bullosa, although it is relatively expensive, time consuming, and not readily available. Immunoreagents have been developed recently to map antigens in the basement membrane on routinely processed specimens. The current study was performed to examine the diagnostic usefulness of immunohistochemistry, as compared with electron microscopic examination, for analyzing routine formalin-fixed paraffin-embedded sections of epidermolysis bullosa. This study investigated 39 consecutively diagnosed cases of epidermolysis bullosa in which both electron microscopic examination and immunohistochemistry were used. In each case, three monoclonal antibodies were used to stain for laminin 1, collagen IV, and keratin. The immunohistochemical patterns were defined as follows: epidermolysis bullosa simplex (laminin, collagen IV, or both at the dermal floor of the blister and keratin at both the dermal floor and the epidermal roof), junctional epidermolysis bullosa (laminin, collagen IV, or both at the dermal floor of the blister and keratin only at the epidermal roof), and dystrophic epidermolysis bullosa (collagen IV, laminin, or both, and keratin all at the epidermal roof). Altogether, electron microscopic examination subclassified epidermolysis bullosa into its three major forms in 37 of the 39 cases (95%), and immunohistochemistry in 33 of the 39 cases (85%). All of the classifiable cases were concordant. Specifically, immunohistochemistry was diagnostic in 10 of 14 (71%) epidermolysis bullosa simplex cases, 14 of 14 (100%) junctional epidermolysis bullosa cases, and 9 of 11 (82%) dystrophic epidermolysis bullosa cases. The most frequent cause for inconclusive immunohistochemical results was failure in staining of the basement membrane with the antibodies to both laminin and collagen IV. In conclusion, the use of immunohistochemistry on routinely processed specimens may be useful for subclassifying epidermolysis bullosa into its major forms in the majority of the cases, although it still cannot fully replace electron microscopic examination or immunofluorescence mapping in the diagnosis of epidermolysis bullosa.

Routine histologic study usually is insufficient to subclassify epidermolysis bullosa (EB); currently, electron microscopic evaluation has been the gold standard. A major advance recently has been made in elucidating the molecular basis of several major forms of EB. Concomitantly, immunoreagents have been developed to map antigens in the basement membrane zone. Some of these reagents facilitate the classification of EB into types and subtypes and can be used as an adjunct informative screening procedure to direct mutation identification efforts using DNA technologies. The current review provides an overview of these recent developments and a more detailed account of the immunohistopathologic diagnosis of EB.