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Cystinosis is an autosomal recessive lysosomal storage disorder with intracellular cystine accumulation caused by mutations in the CTNS gene. We present a case of a 48-year-old woman with a history of cystinosis and squamous cell carcinoma treated with Mohs micrographic surgery where widespread deposition of cystine crystals were noted on frozen sections of the Mohs layers. These were rectangular to polygonal refractile crystals within the cytoplasm of dermal fibroblasts and macrophages which were highlighted by polarized light microscopy. This case illustrates the use of frozen section processing to demonstrate the presence of intracellular cystine crystals. Moreover, because patients with cystinosis may be predisposed to developing carcinomas postrenal transplantation, Mohs surgeons should be aware of this unusual phenomenon when evaluating the slides.

Accurate and complete pathology reports are critical for the optimal management of cancer patients. Protocols for the pathologic reporting of Merkel cell carcinoma (MCC) have been developed independently by the Royal College of Pathologists (UK) and the College of American Pathologists. In this study, data elements for pathologic reporting of MCC were analyzed by an international panel of pathologists and clinicians with the aim of developing a common, internationally agreed upon dataset useful for clinical practice. The International Collaboration on Cancer Reporting expert review panel developed a protocol containing "core" (required) and "noncore" (recommended) elements. Core elements were defined as those that had evidentiary support and were unanimously agreed upon by the review panel as essential for the clinical management, staging, and/or assessment of prognosis in patients with MCC. Noncore elements were those considered to be clinical of interest, but with lesser degrees of supportive evidence or nonactionable implications. Ten core data elements for pathology reports on primary MCC were defined. Development and agreement on this evidence-based protocol at an international level was accomplished in a timely and efficient manner. The template developed for melanoma reporting was used as a structural base for this initiative. It is applicable to, and may facilitate the development of, protocols for other tumor types. Widespread utilization of an internationally agreed upon structured pathology dataset for MCC can be expected to lead to improved patient management. It should also facilitate collaborative clinical research.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Cronkhite-Canada syndrome is an acquired inflammatory polyposis syndrome in which alopecia, onychomadesis and hyperpigmentation occur concurrently with gastrointestinal symptoms. The pathophysiology of alopecia in Cronkhite-Canada syndrome has not been definitively elucidated. We present evidence for alopecia areata incognita as a possible mechanism of hair loss.

Background Anagen effluvium with reversible scalp alopecia is a known side effect of chemotherapy. However, there are an increasing number of reports in the literature documenting permanent alopecia in patients treated with taxanes. Objective We sought to describe the clinicopathologic features in breast cancer patients who underwent treatment with taxanes and adjuvant hormonal chemotherapy. Methods We reviewed the clinical and histopathologic information of a cohort of 10 patients treated with taxanes and adjuvant hormonal chemotherapy. Results We have observed 3 types of clinical patterns of alopecia (types A, B, and C), and have validated the histopathologic features showing alopecia areata–like and female pattern hair loss. Limitations The study was based on a small sample size and retrospective retrieval of clinical information and histopathologic review of posttreatment slides. Conclusions We hypothesize a clinicopathologic model of hair follicle cycle disruption in response to the chemoinflammatory and hormonal insults to the hair follicles resulting in permanent alopecia. Clinicopathologic correlation is paramount to the understanding of the morphobiologic pathways in chemotherapy-induced alopecia caused by taxanes and adjuvant hormonal treatment.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. Mycosis fungoides classically presents in the skin as patches, plaques, tumors, or erythroderma, progressing to involve the lymph nodes and peripheral blood. The many clinical variants, with different histologic patterns, and the subtle early clinical and histologic changes may delay early diagnosis and present a diagnostic challenge for clinicians. The greatest challenge in diagnosis is the pre-mycotic stage, which may closely resemble eczematous or psoriasiform dermatitis clinically and histologically. The persistence of lesions and inadequate response to treatment are the first warning signs. Later stages of MF have a poor prognosis with poor therapeutic response and fatal outcome. We describe a 72-year-old man, who presented with a two-year history of an unusual eruption, which started on the abdomen, around the waistline, and gradually spread to involve his back, trunk, and buttocks. Clinically, the skin eruption presented as tiger-like stripes. The diagnosis was confirmed after histopathologic examination. The patient was treated with NB-UVB phototherapy with marked improvement.

Background We compared the use of an immunohistochemical (IHC) method using a monoclonal antibody to BRAF V600E (which detects the main BRAF mutation) with existing DNA probe screening in tissue samples from 71 patients with malignant melanoma. Materials and methods Paraffin blocks were cut to provide consecutive slides for haematoxylin and eosin staining, and for known positive micro-array DNA control material. IHC was performed by the Optiview detection system. All slides were scored independently by the clinical lead and the laboratory lead using a positive/negative system. Results The DNA method found 26 samples to be positive, the IHC found 21 to be positive, giving a sensitivity value for IHC of 80.8%. However, all of the 45 samples found to be negative by DNA were also negative by IHC, giving a specificity of 100%. There were 66 instances of full agreement, giving a concordance of 93%. Together, these data give a kappa statistic of 0.843, indicating very good agreement. Conclusion The data reveal a very close link between the two methods, supporting the use of the V600E as a primary screen for BRAF mutations in malignant melanoma. Samples found to be negative by this method may be retested by the DNA probe method. IHC detection conserves patient DNA from tumour blocks as only one section is required to perform the assay. The V600E antibody method is considerably cheaper and faster than the DNA probe assay, with a turn-around time of 24-48 hours, enabling more rapid clinical management.

Background Few histologic studies describe the histopathologic aspects of scleromyxedema. Objective We sought to describe the histopathologic and immunohistochemical features of scleromyxedema in a large series of patients. Methods We studied all the cases with scleromyxedema diagnosed between 2000 and 2014 at participating centers. Sections with hematoxylin-eosin and special stains were examined. Immunohistochemistry for CD3, CD4, CD8, CD20, CD68, and factor XIIIa was performed in 10 cases. Results A total of 44 skin biopsy specimens from 34 patients were reviewed. Two different histopathologic patterns were observed: the classic microscopic triad (dermal mucin deposition, fibroblast proliferation, fibrosis) was identified in 34 specimens, whereas an interstitial granuloma annulare–like pattern was found in 10 specimens. A superficial perivascular infiltrate with T lymphocytes was found in all specimens whereas an interstitial proliferation of CD68 + epithelioid cells was identified in the 10 specimens with an interstitial granuloma annulare–like pattern. Elastic fibers were largely lost, explaining the redundant folds of the disease. Limitations This was a retrospective study. Conclusions Scleromyxedema shows 2 histopathologic patterns, including the classic type with the microscopic triad of mucin, fibroblast proliferation and fibrosis, and an interstitial granuloma annulare–like pattern. Recognition of these histologic presentations expands the spectrum of scleromyxedema and highlights the difficulty in diagnosing this disabling condition in the absence of a clinicopathological correlation.

Woolly hair nevus is a mosaic disorder characterized by unruly, tightly curled hair in a circumscribed area of the scalp. This condition may be associated with epidermal nevi. We describe an 11-year-old boy who initially presented with multiple patches of woolly hair and with epidermal nevi on his left cheek and back. He had no nail, teeth, eye, or cardiac abnormalities. Analysis of plucked hairs from patches of woolly hair showed twisting of the hair shaft and an abnormal hair cuticle. Histopathology of a woolly hair patch showed diffuse hair follicle miniaturization with increased vellus hairs.

Deriving from the Greek word λειχήν for "tree moss" and the Latin word planus for "planar," lichen planus is a relatively uncommon and heterogeneous cutaneous disorder that typically develops in middle-aged adults. Despite the significant clinical burden associated with the disorder, little well-conducted molecular research has been undertaken, possibly because of heterogeneity impeding consistent and confident phenotyping. The multiple variants of lichenoid disease bear overlapping clinical and pathologic features despite manifesting as distinct clinical disorders. The first article in this 2-part continuing medical education series provides a comprehensive overview of the clinical and pathologic characteristics of cutaneous lichenoid dermatoses and links these manifestations to recent advances in our understanding of the underlying pathobiology of such diseases.

Having reviewed the diverse clinical subtypes of lichenoid disease and the postulated molecular basis thereof in the first article in this 2-part continuing medical education series, we discuss herein the existing and emerging treatment strategies in the most common clinical forms of lichenoid inflammation and provide an overview of their pharmacodynamics and evidence base. The scope of this review is not to exhaustively discuss treatment modalities for all lichenoid variants discussed in the previous article of this series. Instead, the focus will be on frequently encountered subtypes of lichen planus and on linking mechanisms of disease with mechanisms of drug action. Future directions and potential avenues for translational research will also be discussed.

“Mutational signatures” are patterns of mutations that report DNA damage and subsequent repair processes that have occurred. Whole-genome sequencing (WGS) can provide additional information to standard diagnostic techniques and can identify therapeutic targets. A 32-yr-old male with xeroderma pigmentosum developed metastatic angiosarcoma that was unresponsive to three lines of conventional sarcoma therapies. WGS was performed on his primary cancer revealing a hypermutated tumor, including clonal ultraviolet radiation-induced mutational patterns (Signature 7) and subclonal signatures of mutated DNA polymerase epsilon (POLE) (Signature 10). These signatures are associated with response to immune checkpoint blockade. Immunohistochemistry confirmed high PD-L1 expression in metastatic deposits. The anti-PD-1 monoclonal antibody pembrolizumab was commenced off-label given the POLE mutation and high mutational load. After four cycles, there was a significant reduction in his disease with almost complete resolution of the metastatic deposits. This case highlights the importance of WGS in the analysis, interpretation, and treatment of cancers. We anticipate that as WGS becomes integral to the cancer diagnostic pathway, treatments will be stratified to the individual based on their unique genomic and/or transcriptomic profile, enhancing classical approaches of histologically driven treatment decisions.

Background: Scleromyxedema is associated with a monoclonal gammopathy and other comorbidities. Its prognostic and therapeutic features are poorly documented because most reports deal with single cases or small series. Objective: We sought to describe the characteristics of patients with scleromyxedema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions, and course. Methods: We conducted a retrospective and prospective multicenter study. Results: We identified 30 patients with scleromyxedema (17 men and 13 women). The mean age at diagnosis was 59 years. The mean delay between disease onset and diagnosis was 9 months. Monoclonal gammopathy was detected in 27 patients. Extracutaneous manifestations were present in 19 patients including neurologic (30%), rheumatologic (23.3%), and cardiac (20%) manifestations. Two patients developed hematologic malignancies. The most common therapies included oral steroids and intravenous immunoglobulins. Although corticosteroids were ineffective, intravenous immunoglobulins (alone or in combination with other drugs) induced complete remission in 4 and partial remission in 9 patients with a mean treatment duration of 2 years. In all, 21 patients were followed up for a mean period of 33.5 months, at which time 16 patients were alive, 12 with and 4 without skin disease. Five patients died: 2 with dermatoneuro syndrome and 1 each with myeloid leukemia, Hodgkin lymphoma, and myocardial insufficiency. Limitations: This is mainly a retrospective study. Conclusions: Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required

We were interested to read the article Frontal Fibrosing Alopecia - Possible Association with Leave-on Facial Skin Care Products and Sunscreens; A Questionnaire Study by Aldoori et al1. The authors sought to identify possible causative environmental factors associated with frontal fibrosing alopecia (FFA). One conclusion was that the use of facial products containing sunscreens might be implicated. This article is protected by copyright. All rights reserved.

Since it was first described by Kossard in 1994, frontal fibrosing alopecia (FFA) has been something of an enigma. The clinical heterogeneity of FFA, its apparent rarity, and investigators' suboptimal access to phenotypically consistent patient cohorts, may all have had a negative impact on delineating disease pathogenesis. Moreover, there is a relative paucity of epidemiologic interventional and basic research studies, and there have been no advances in translational therapeutics, unlike for other inflammatory dermatoses, such as alopecia areata (AA). Dermatologists anecdotally describe an increasing incidence in FFA over the last decade, which has led to the notion that the disorder may be induced by unknown environmental triggers. On the other hand, segregation of FFA in some families lends support to an unexplored genetic element implicated in disease pathogenesis. We herein review what is known about the pathobiology of FFA and formulate working hypotheses to advance insight into this intriguing hair disorder. This article is protected by copyright. All rights reserved.

Primary vulvar carcinoma is rare and thought to arise from either anogenital mammary-like glands or native apocrine sweat glands. The diagnosis is predominantly based on tumor morphology with supportive evidence from immunohistochemical staining and exclusion of a primary breast carcinoma. The primary modality of treatment is surgery, while optimal managment of advanced disease is unclear. We present the case of a lady who had metastatic recurrent apocrine carcinoma expressing estrogen receptors, who had a complete response assessed by PET-CT scanning after 7 months of tamoxifen therapy. The report includes a discussion of the histological diagnosis and assessment of response to treatment by PET-CT scanning.

Cutaneous collagenous vasculopathy is characterized by generalized cutaneous telangiectasia and unique microscopic and ultrastructural vascular changes, consisting of marked collagen deposition within the vascular walls of the post-capillary venules in the superficial dermis. There are only 4 previous cases described in the medical literature, all in males, mostly middle-aged. We have recently seen two female patients with clinical and histopathologic features diagnostic of cutaneous collagenous vasculopathy, indicating that it is not restricted to males. As cutaneous collagenous vasculopathy can be clinically indistinguishable from generalized essential telangiectasia, and histopathologic studies are rarely performed for this condition, it is likely that cutaneous collagenous vasculopathy frequently passes unrecognized, but it may be more common than previously thought.

Background In frontal fibrosing alopecia (FFA), scalp alopecia dominates the clinical picture. However, eyebrow loss and hair loss in other body sites may also occur; this has been documented clinically, but rarely histopathologically. We describe the clinicopathological findings of 13 cases of FFA, with histopathologic data from the scalp, eyebrow, and body hair. Methods Thirteen patients with a diagnosis of FFA, seen between 2006 and 2008, were included. Scalp biopsies were performed in all patients for histology and direct immunofluorescence (DIF). Biopsy specimens for histology were taken from the eyebrow in 6 patients and from the upper limb in 5 patients. Results All 13 patients were female, 11 of whom were postmenopausal. The median age at onset of alopecia was 57 years. Clinical examination revealed a band of frontal hairline recession in all patients. Eyebrow loss was present clinically in all patients, with loss of body hair in 10 of 13. Histopathologic examination of the scalp, eyebrow, and upper limb skin biopsy specimens showed similar features, including a marked reduction in the number of hair follicles and a perifollicular lymphoid cell infiltrate with perifollicular fibrosis. Direct immunofluorescence was negative in all cases. Limitations Not all patients consented to biopsies of the eyebrows or upper limbs. Conclusion Eyebrow and peripheral body hair loss is not uncommon in FFA—a finding that is likely underreported. We have demonstrated that alopecia of the upper limbs in FFA is indeed common and, histopathologically, shows features of lichen planopilaris and scarring, similar to findings in the scalp and eyebrows. Consequently, the process of lichen planopilaris with scarring alopecia is generalized rather than localized only to the frontal scalp and eyebrows.

Early lesions of lichen sclerosus et atrophicus (LSA) may present as a mild lichenoid tissue reaction, occasionally together with basilar epidermotropism, mimicking early cutaneous T-cell lymphoma, mycosis fungoides (MF) variant. We report a case of extragenital LSA in which both histological patterns were present in the same clinically homogenous and stable lesion. A 27-year-old man presented with a history of white atrophic plaques on the trunk. A biopsy of an abdominal lesion revealed epidermal thinning, a superficial perivascular lymphoid cell infiltrate with focal epidermotropism, mild nuclear atypia and perinuclear halos. Immunophenotyping showed decreased CD5 and CD7, with a slight predominance of CD8-positive T-lymphocytes. All these changes were suggestive of MF. However, a repeat biopsy 3 months later from the same stable plaque revealed features diagnostic of LSA. LSA mimicking early MF histologically has been reported in genital skin. Conversely, MF may clinically and histopathologically resemble LSA. With gene rearrangement studies, clonal proliferation may not be detected in early MF but has been reported to occur in LSA. Awareness of the histopathologic spectrum of LSA within a stable plaque is important to avoid a potential diagnostic pitfall, and should prompt a repeat biopsy.

Nondermatophytic toenail infection with Scopulariopsis brevicaulis is rare, but may occur often in association with dermatophytes. We report a case of an 84-year-old man who presented with onychomycosis of the big toenail. Histopathologic examination of the avulsed nail showed evidence of S. brevicaulis coinfection with a dermatophyte, despite negative mycology results for the latter. Our case underscores the importance of histopathologic examination of nail specimens as an additional invaluable tool in the diagnosis of onychomycosis, as it may unmask false-negative mycology findings.

Background Scleromyxedema is associated with a monoclonal gammopathy and other comorbidities. Its prognostic and therapeutic features are poorly documented because most reports deal with single cases or small series. Objective We sought to describe the characteristics of patients with scleromyxedema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions, and course. Methods We conducted a retrospective and prospective multicenter study. Results We identified 30 patients with scleromyxedema (17 men and 13 women). The mean age at diagnosis was 59 years. The mean delay between disease onset and diagnosis was 9 months. Monoclonal gammopathy was detected in 27 patients. Extracutaneous manifestations were present in 19 patients including neurologic (30%), rheumatologic (23.3%), and cardiac (20%) manifestations. Two patients developed hematologic malignancies. The most common therapies included oral steroids and intravenous immunoglobulins. Although corticosteroids were ineffective, intravenous immunoglobulins (alone or in combination with other drugs) induced complete remission in 4 and partial remission in 9 patients with a mean treatment duration of 2 years. In all, 21 patients were followed up for a mean period of 33.5 months, at which time 16 patients were alive, 12 with and 4 without skin disease. Five patients died: 2 with dermatoneuro syndrome and 1 each with myeloid leukemia, Hodgkin lymphoma, and myocardial insufficiency. Limitations This is mainly a retrospective study. Conclusions Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required.

High-pressure paint guns deliver paint at approximately 3000 pounds per square inch. At this pressure, paint will penetrate the skin and spread quickly through fascial planes and tendon sheaths. The present case is that of a lesion from the finger of a 35-year-old white male in whom a history was initially unavailable. Histologic examination revealed diffuse fibrohistiocytic proliferation and giant cells, with numerous darkly pigmented, uniformly small-sized particles throughout the lesion. The initial impression was that of a giant cell tumor of tendon sheath. However, the pigment particles were negative for Perls stain, and polariscopic examination revealed clear refractile fragments. These findings raised the possibility that the lesion was the result of a traumatic event. On further inquiry, it was revealed that the patient had sustained a high-pressure paint-gun injury 1 year earlier. The simulation, histopathologically, of a giant cell tumor of tendon sheath by a high-pressure paint-gun injury has not, to our knowledge, been reported previously, nor has the histologic finding of small, uniformly sized pigment particles and polarizable refractile fragments in this particular type of injury.

A recent paper by Torres‐Cabala et al.1 published in the JCP reports that about 10% (13/136) of small (3 mm or less in size) dysplastic melanocytic nevi show severe architectural disorder, which, however, is almost never coupled with severe cytologic atypia. It is therefore suggested that, in order to avoid overdiagnosis of melanoma, the significance of architectural changes of small melanocytic lesions must be interpreted with caution; the small size of the lesion hampers the evaluation of some of these criteria (symmetry, confluence of junctional nests and degree of single cell proliferation).

Atypical moles (dysplastic nevi) are important markers for persons at increased risk for developing melanoma 1, 12 and are potential precursors to melanoma. 9 The clinical characteristics that distinguish an atypical mole are those normally attributed to melanoma, the ABCD s of dermatology: (A) asymmetrical shape or contour, (B) border irregularity, (C) color variegation, and (D) diameter greater than 6 mm. 8, 32 These criteria help differentiate atypical moles from common nevi clinically; however, because the criteria for melanoma are similar to those for atypical moles, a tendency to overdiagnose melanoma results. The difference between an atypical mole and melanoma is primarily dependent on the extent of these features; that is, the more dysmorphic the lesion, the more likely is a diagnosis of melanoma. Reliably differentiating atypical moles from early melanomas poses a considerable challenge to the clinician. Dermatologists correctly diagnosis melanoma about 65% of the time. 10, 15, 18, 24 In an attempt to improve on this rate, various noninvasive methods have been investigated as possible aids for the early diagnosis of melanoma, the most promising being dermoscopy (epiluminescence microscopy [ELM]). 28, 29, 33, 37 Dermoscopy increases the diagnostic accuracy for melanoma, particularly when the clinician is experienced with its use. 4, 5, 16, 25, 26, 28, 37 Despite the improvement in diagnostic accuracy with dermoscopy, a significant number of melanomas are missed by this technique. The reported sensitivity of dermoscopy for melanoma ranges from 62% to 94%. 5, 6, 16, 25, 26, 28, 34, 37 Although pathognomonic dermoscopic findings for melanoma have not been identified, 36 several are highly suggestive. These findings include an irregular pigment network with abrupt margins, radial streaming, pseudopods, depigmented areas, a whitish veil, brown globules and black dots of variable size and irregular distribution, and homogeneous areas. 14, 23, 28, 29, 34, 36 In general, a combination of features must be present to conclude with any certainty that a given lesion is benign or malignant. 17, 28, 36 Up to 10% of melanomas may be featureless, 22 probably accounting for the high rate of false-negative results reported by some investigators. 5, 26 In our study discussed herein, the usefulness of the aforementioned dermoscopic features is reexamined in differentiating early melanomas from atypical moles. Attempts also are made to identify potential new criteria for early melanoma detection by subjectively quantifying or characterizing dermoscopic structures.

A 26-year-old Libyan woman presented with asymptomatic nodulo-ulcerative skin lesions present for 1 year. Three years prior to presentation, she had experienced a nasal discharge followed by the development of a nodule in the nasal cavity and a plaque on the hard palate. These lesions had gradually increased in size and ulcerated, resulting in perforation of the nasal septum and palate. Two years later, the patient noticed the appearance of skin lesions: a nodule on the right thumb and numerous nodulo-ulcerative lesions on the extremities. General physical examination was normal with no significant lymphadenopathy. Examination of the oral cavity revealed perforation of the distal nasal septum, with a perforated nodular plaque involving the entire palate, associated with subluxation of the upper incisors (Fig. 1a). On skin examination, multiple firm nodules and nodulo-ulcerative lesions with a central eschar and raised margins were observed. The lesions ranged in size from 0.5 to 5 cm and were distributed on the right hand and fingers, left upper arm (Fig. 1b), left calf, and right thigh. Routine laboratory investigations (liver function tests, serum calcium, electrolytes, lipid profile, urine and stool culture studies) were normal. Immunoelectrophoresis disclosed normal levels of immunoglobulins IgG, IgA, and IgM. Serologic studies for human immunodeficiency virus (HIV) and syphilis, and a tuberculin test, were all negative. A Giemsa-stained tissue smear was negative for Leishmania tropica organisms. Radiological studies disclosed a slight haziness of the maxillary sinuses with perforation of the nasal septum. A chest X-ray was normal. Histopathologic examination of biopsies taken from both the palate and from ulcerated and nonulcerated skin lesions was performed, and all showed similar findings. The biopsy of a nonulcerated skin lesion showed pseudoepitheliomatous epidermal hyperplasia with neutrophilic microabscesses (Fig. 2a). A dermal diffuse and nodular granulomatous mixed infiltrate of lymphocytes, histiocytes, giant cells, numerous eosinophils, and neutrophilic microabscesses was seen in all tissues examined. Septate hyphae were present both within giant cells and free in the dermis (Fig. 2b). The hyphae were branching at a 45 degrees angle and were positive on periodic acid-Schiff and Grocott methenamine silver stains (Fig. 2c). Fungal culture studies of material taken from an ulcerated skin lesion grew Aspergillus flavus. Blood cultures were negative for Aspergillus sp. or other microorganisms. The patient was treated with intravenous amphotericin B, but the medication was discontinued due to her intolerance to the drug. She was subsequently lost to follow-up.

Extramammary Paget disease (EMPD) is a heterogenous entity representing either an intraepidermal adenocarcinoma in situ with apocrine differentiation or an expression of underlying malignancy of the skin or of the intestinal or genitourinary tract. The coexistence of EMPD with a benign underlying hidradenoma papilliferumn (HP) is, however, exceptional. We present the case of a 79-year-old woman with diffuse and patchy gray-white lesions involving her left vulva as well as an underlying 0.7-cm asymptomatic firm nodule. Histologically, the epidermis and dermis showed features characteristic of EMPD and HP, respectively. Malignant transformation in HP giving rise to EMPD in the overlying epithelium has been reported. In our case, however, failure to demonstrate continuity between the two lesions together with the lack of cytologic atypia, mitoses, and necrosis in the HP lends additional support to the possibility that the HP is "innocent" and that its association with EMPD is thus coincidental. A common histogenetic derivation of these two lesions from the mammary-like glands or from related germinative cells in the epidermis is suggested to explain this rare presentation.

We report a case of localized bullous pemphigoid (BP) in a woman patient with primary lymphoedema tarda. There is only one previous case reported of localized pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow circulation in the lymphatic vessels, increased capillary permeability with preferential localization of antibodies in the area, and potential cleavage of the epidermal junction due to increased hydrostatic pressure leading to autoimmunity, have all been advocated as possible pathogenic mechanisms. Nevertheless, we consider that the mechanism by which localized pemphigoid arises on lymphoedema remains elusive, based on a previous case of generalized BP sparing an area of postsurgical lymphoedema.

We report a unique case of a congenital keratinocytic naevus associated with severe alopecia, onychodysplasia and palmoplantar involvement in a 13-year-old girl. The lesions, consisting of scaly, spinous and verrucous papules and plaques, mainly followed Blaschko's lines and have remained unchanged since birth. The predominant histopathological picture was that of a column of parakeratosis overlying the eccrine ostia and hair follicles. This is the first case of a systematized keratinocytic naevus characterized by histopathology of eccrine and hair follicle porokeratosis and a widespread bilateral involvement. This may be a distinct entity to be included in the differential diagnosis of linear, hyperkeratotic dermatoses. We suggest its classification as systematized porokeratotic eccrine and hair follicle naevus.

Background: Hyperpigmentation is a side effect of several medications, including amiodarone, bleomycin, chlorpromazine, and minocycline. Objective: The purpose of this study is to describe the clinical and light microscopic findings in 4 patients with imipramine-induced hyperpigmentation and to better understand its origin. Methods: All 4 patients underwent a skin biopsy for light microscopy. In 1 patient, a biopsy specimen was obtained for electron microscopy. Tissue from patient 1 was analyzed with a mass spectrophotometer, and energy-dispersive x-ray analysis was performed on tissue from patients 1 and 2. Results: All 4 women had been taking imipramine for at least 2 years. Hyperpigmentation occurred in a photodistribution on the face, arms, and backs of the hands. Light microscopy in all cases demonstrated golden-brown granules in the superficial dermis, which were strongly positive for Fontana-Masson stain. Electron microscopy demonstrated areas of electron-dense inclusion bodies within macrophages, which were distinct from melanosomes. Mass spectrophotometric and energy-dispersive x-ray analysis of the electron-dense bodies showed the presence of sulfur atoms, and no peak corresponding to that expected for imipramine was found. A peak closely corresponding to phaeomelanin, a sulfur-containing compound, was found. Conclusion: Hyperpigmentation is a side effect of long-term imipramine use. It may result from the deposition of melanin in an unusual form. The melanin pigment is possibly complexed with a metabolite of imipramine, and does not represent the deposition of imipramine in its native form. (J Am Acad Dermatol 1999;40:159-66.)

Skeletal muscle (SM) regeneration is a pleomorphic yet benign reaction pattern that follows injury to SM and has been reported to simulate histologically various malignancies such as squamous cell carcinoma and rhabdomyosarcoma. A 61-year-old man presented with a 4-month history of an enlarging nodule on the upper lip following blunt trauma. An initial punch biopsy was non-diagnostic. A deeper biopsy revealed a multilobular proliferation of atypical and pleomorphic cells with vesicular nuclei, prominent nucleoli, and large amphophilic cytoplasm. Immunoperoxidase studies showed these cells to be positive for muscle-specific actin and desmin and negative for S-100 protein and smooth muscle actin. Based on these findings, a diagnosis of skeletal muscle regeneration (SMR) was made. To our knowledge, this is the first report of SMR presenting clinically as a rapidly growing cutaneous nodule on the lip following blunt trauma.

BACKGROUND: Macromelanosomes are melanin-containing granules characterized by their large size and spherical or ellipsoidal morphology. They are reported to be present in a variety of pigmented skin lesions, including lentigines. However, there is limited information on macromelanosomes in malignant melanocytic proliferations. The margins of a lentigo maligna/malignant melanoma in situ (LM/MMIS) and solar lentigo share morphological similarities, including lentiginous proliferation of melanocytes, increased melanin in basal cell layer keratinocytes, and solar elastosis. This may represent a potential diagnostic pitfall, particularly in small biopsies. We sought to identify whether the presence of macromelanosomes at the lesional margins of LM/MMIS may represent a morphological clue in distinguishing between these 2 entities. METHODS: Data were obtained from 2 different institutions between 2001 and 2010. 619 cases of solar lentigo and 117 cases of LM/MMIS were screened for the presence and distribution of macromelanosomes. RESULTS: 25 of 117 cases (21%) of LM/MMIS had macromelanosomes identified at the lesional margins, compared with 7 of 619 (1%) of solar lentigo cases (P < 0.0001). CONCLUSIONS: Our data demonstrate that the identification of macromelanosomes within a lentiginous melanocytic proliferation should prompt further evaluation to rule out the possibility of a contiguous LM/MMIS, particularly in a small biopsy.

Catamenial dermatoses are unusual, cyclic, perimenstrual reactions to hormones produced during the menstrual cycle. They occur in a variety of clinical presentations, including urticaria, eczema, fixed drug eruptions, erythema multiforme and anaphylaxis. Autoimmune progesterone dermatitis is the most common, and is caused by an autoimmune response to endogenous progesterone in women of reproductive age. We report a case of catamenial dermatosis in a 42-year-old Jamaican woman with a 10-year history of cyclic blistering and ulcerative eruptions of her mouth and limbs. Her symptoms were fully in keeping with a Stevens-Johnson-type reaction, and were associated with production of prostaglandins occurring during her menstrual cycle.

EMLA(®) (eutectic mixture of local anesthetics, 2.5% each of lidocaine and prilocaine in an oil and water emulsion) is used as a topical anesthetic. We report three cases of EMLA(®) -induced histopathologic changes on the vulvar epithelium. While there are some similar histopathologic features to those reported in extragenital skin, we describe additional findings on vulvar epithelium, which, to our knowledge, have not been reported previously. The patients presented with clinical signs suggestive of lichen sclerosus or erosive lichen planus (LP), but were all confirmed histopathologically as LP. The biopsy was taken after 15 min of EMLA(®) application and intradermal injection of 1% lidocaine. Blistering prior to intradermal lidocaine and the biopsy procedure was observed in two patients. The histopathologic changes observed in the epithelium included pallor of the upper epidermis, mild spongiosis, intraepidermal subcorneal and suprabasal acantholysis, congestion of the papillary dermal capillaries and extravasated erythrocytes. Basophilic granules were present, but rare, while the necrosis with multifocal clefting was more marked than in extragenital skin. It is important to be aware of these changes occurring on genital mucosa; these may occur in the absence of clinical signs and may obscure the primary underlying pathology, thus representing a diagnostic pitfall.

Exceedingly rare cases of neoplasms with clear-cut histopathologic features of benignity can show locoregional or even distant spread. Such cases can become putative examples of "benign metastasis" when a completely favorable clinical outcome is documented after an adequately long follow-up. We report 8 cases of morphologically benign clear cell nodular hidradenoma (CCNH) with lymphatic involvement. In 5 cases the cutaneous tumor showed small foci of intravascular deposits of neoplastic cells; in 2 cases the cutaneous tumor presented with a synchronous tumor in a regional node; in 1 case a nodal location CCNH was found with no evidence of any primary in the skin. All the cases were treated with conservative surgery and none of them showed disease progression during a follow-up period ranging from 2 to 11 years. These data suggest that in the absence of other histopathologic features of malignancy, lymphatic spread in CCNH can still carry an excellent prognosis and can be therefore considered as an example of "benign metastasis." As the latter concept can be set forth only after an uneventful long-term follow-up, in routine practice, cases of morphologically benign CCNH with lymphatic involvement are best labeled "atypical CCNH," or "CCNH-like tumor of uncertain malignant potential."

The histopathologic assessment of a scalp biopsy for alopecia relies largely on the quality of the specimen provided for evaluation. There are a number of different protocols in the literature which have been proposed over the years, but no consensus has yet been reached as to the appropriate number of biopsies to be taken, or to which sectioning technique is the gold standard for achieving the best diagnostic yield. We herein review the pros and cons of the various protocols and share the experience with our St John's protocol.

The objective of follow-up examinations of patients who have had Stage I invasive malignant melanoma is the early detection of local recurrences, metastases, and new primary melanomas. Model schedules for follow-up intervals were developed based on a survey of eight physicians. These melanoma experts agree that regular follow-up examinations are indicated and that the time intervals between examination vary according to the thicknesses of the melanomas. The patient follow-up schedule derived is: for melanomas up to 0.75-mm thick, every 6 months for years 1 and 2, and annually for years 3, 4, and 5; for melanomas 0.76-1.50 mm thick, every 3 months for years 1 and 2, semi-annually for years 3, 4, and 5; and for melanomas > 1.50 mm thick, every 3 months for years 1, 2, and 3, and semi-annually for years 4 and 5. After the fifth year, the recommendation is to examine all patients annually for life because of the continued risk for recurrences and new primary melanomas. For those individuals at especially high risk for developing multiple primary melanomas more frequent examinations may be appropriate.

CD20 is a transmembrane protein that is expressed by B cells during their development and is, therefore, commonly used to label cells of B lineage in lymphoid infiltrates. CD20-positive T-cell lymphoma is infrequent but well recognized. Cases reported in the literature show a variety of clinical and histoimmunochemical profiles. Primary cutaneous CD20-positive T-cell lymphoma is vanishingly rare; only eight cases have been previously reported. We present two new cases of this entity and describe their clinical, histological and immunohistochemical features. CD20 is a highly specific B-cell marker. However, it has been reported in a subset of normal T-cells in peripheral blood and bone marrow of healthy individuals. This subset of T-cells also expresses more often CD8 and g/d than the CD20-negative T-cells. Two main theories have been postulated to explain the expression of CD20 by neoplastic T-cells. The first possibility is that these lymphomas develop from the CD20-positive subset of normal T-cells. The second theory regards CD20 as an activation marker. Prognostic implications and therapeutic options of T-cell lymphomas with positivity for CD20 remain to be elucidated.

We describe a rare case of primary cutaneous marginal zone B-cell lymphoma (PCMZL) in a 33-year-old male affected by hepatitis B virus (HBV)-related chronic active hepatitis. The patient presented with multiple cutaneous papulonodular lesions characterized by polymorphic immunomorphology, with inverse pattern of immunoglobulin light chain restriction in two different lesions, coupled with mucin deposition and anetoderma in a third lesion. The involution of lesions of PCMZL with secondary anetoderma has been previously described, but this has not been reported in the context of multiple lesions showing differing immunoglobulin light chain restriction. We speculate that these findings may be secondary to a variable interaction between a chronic antigenic stimulus (i.e. HBV) and its specific immune response.

Purpose We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. Patients and Methods Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. Results The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. Conclusion This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

Determining the underlying etiology of recurrent erythema multiforme (EM) can be a difficult endeavor. Although infection with herpes simplex virus (HSV) has been implicated in some cases, the precise trigger of a given patient's recurrent EM often remains elusive. We discuss the case of a woman with a recurrent blistering eruption that was clinically and histopathologically consistent with EM. An investigation into the etiology of the patient's EM suggested that HSV was not the causative factor but instead pointed toward a hormonal influence that we interpret as autoimmune progesterone dermatitis (APD). This case is presented to highlight the importance of considering hormonal triggers in women with recurrent EM that consistently flares during the luteal phase of the menstrual cycle, the point at which serum progesterone levels peak. A brief review of the literature regarding the diagnosis, histopathology, etiology and treatment of APD is further provided.