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Malignant melanoma (MM) may display highly variable phenotypic diversity, sometimes associated with loss of immunohistochemical melanocytic markers and acquisition of nonmelanocytic lineage of differentiation. Primary cutaneous MM with rhabdomyosarcomatous differentiation is extremely rare with only 5 reported cases in the literature. To date, a chronological progression of a MM to rhabdomyosarcoma has not been conclusively documented. A 96-year-old man underwent a re-excision of an "atypical fibroxanthoma" of the forearm, which revealed a small lentigo maligna melanoma associated with a dominant dermal high-grade spindle cell nodule admixed with a population of malignant polygonal epithelioid cells. On immunohistochemical studies, the spindle cells were completely negative for all melanocytic markers, whereas a small population of polygonal neoplastic cells at the periphery was positive for Desmin and Myo-D1, supporting early rhabdomyosarcomatous transformation. Several subsequent re-excisions demonstrated merely nodules of malignant pleomorphic epithelioid cells with rhabdomyosarcomatous differentiation and devoid of melanocytic markers. In addition, both rhabdomyosarcomatous component and original MM displayed identical mutations. Therefore, the histologic, immunohistochemical, and molecular findings documented for the first time a chronological progression from an invasive MM to a pleomorphic rhabdomyosarcoma through an intermediate stage of undifferentiated sarcoma/atypical fibroxanthoma. Interestingly, subsequent recurrences of pure rhabdomyosarcomatous component displayed skip lesions/microsatellitosis, marked tumor-infiltrative lymphocytes, and rare junctional nests of rhabdomyosarcomatous cells in the epidermis, histologic features that were not described in primary cutaneous rhabdomyosarcoma and therefore could serve as morphologic clues to the diagnosis of rhabdomyosarcomatous transformation in an MM.

One of the pathogenic causes of cutaneous inflammatory pseudotumors is chronic localized fibrosing leukocytoclastic vasculitis (CLFLCV), a vasculitic reaction pattern seen in granuloma faciale (GF), a localized vasculitis, and erythema elevatum diutinum (EED), a generalized vasculitis. Patients with myelodysplastic syndromes (MDSs) are at risk for a diverse spectrum of cutaneous neutrophilic dermatoses such as EED. Herein, we report a 74-year-old man who presented with a large ulcerative, fungating tumor affecting the right flexor ankle caused by CLFLCV. During his workup and management, MDS and Philadelphia chromosome-negative chronic myeloid leukemia was diagnosed. Surgical excision of the inflammatory mass promptly triggered tumor recurrence, whereas antineutrophil therapy (dapsone coupled with hydroxyurea, and prednisone) lead to tumor regression. Histopathologic examination revealed an eosinophilic-rich small-vessel neutrophilic vasculitis associated with storiform and angiocentric fibrosis (GF-like). In the regions of fibrosis, dilated lymphatic and vascular spaces were numerous, some of which were congested with small CD3-positive lymphocytes (intralymphatic and intravascular lymphocytosis). These findings indicate coexisting localized lymphedema. By direct immunofluorescence, IgM and C4d vessel deposits were detected. The pathogenesis of the fibrotic nodules and plaques of CLFLCV is suspected to be due to recurring bouts of immune-complex vasculitis, creating a cycle of vessel damage followed by reparative granulation tissue. Poor lymphatic drainage may be the underlying factor initiating and maintaining recurrent, localized episodes of immune-complex vasculitis and progressive fibrosis. Although his tumor histopathology resembled GF-eosinophilic rich CLFLCV-the clinical context points to a solitary and paraneoplastic case of EED.

Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0-9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.

The co-existence of Darier disease (DD) and acrokeratosis verruciformis of Hopf (AKV) has been noted for decades and the relationship between the 2 entities remains controversial. Although, it has been shown that both diseases are associated with mutations in ATPA2 gene, it is yet to be determined if they are the same disease, or separate but allelic, or interlinked in some other fashion. Herein, the authors report the case of a 13-year-old girl presenting with shiny flat-topped verruca plana-like papules, on the dorsal hands and feet and red-brown crusted papules on her forehead and along the sides of her neck. Histological evaluation of a wart-like lesion shows features of AKV, a verruca plana-like histopathology and focal acantholytic dyskeratosis. Forehead biopsy also demonstrated focal acantholytic dyskeratosis supporting the diagnosis of DD. Polymerase chain reaction for human papillomavirus (HPV) DNA detected HPV-17, a human betapapillomavirus in the verruca plana-like papule. Cytoplasmic expression of the L1 capsid expression was seen in areas of hypergranulosis. The presence of productive betaPV infection in the setting of DD and AKV suggests a susceptibility to HPV infection.

Introduction Morbihan disease (MORD) is rare with only 45 clear-cut cases previously reported. Histopathologic findings are supposed to be nonspecific. We report 14 patients and review the previous cases. Objectives To characterize the clinicopathologic findings, outcomes, and immunophenotype of MORD. Material and methods Inclusion criteria were a clinical picture of persistent, nonpitting edema affecting the mid and or upper third of the face and histopathological findings fitting previous reports and exclusion of other entities. Results The majority of our patients were males (71.5%) with a male/female ratio of 10/4. The mean age when diagnosed was 58.8 years. Eyelids and forehead were the most frequently involved areas. Two of the patients presented previous rosacea. Most constant histopathological findings were lymphatic vessel dilatations in the upper dermis and the presence of mast cells (7.5 in 10 high-power field as a mean). Mild edema was also present in most of the cases. Granulomas were found in 7 of the cases, and immunostaining with CD68 and CD14 only revealed an additional case. Conclusions MORD occurs more in middle-aged males, not associated with rosacea and mostly affects eyelids and forehead. Granulomas are not mandatory for the diagnosis. Histopathology of MORD fits within the spectrum of localized lymphedema.

Neutrophilic dermatosis (ND) confined to postmastectomy lymphedema, localized Sweet syndrome, is a newly recognized disease. In this study, the authors describe a 44-year-old obese woman with chronic myelogenous leukemia in molecular remission on dasatinib therapy, who presented with a painful urticarial eruption limited to lipo-lymphedematous skin and accompanied by malaise, episodic fever, diarrhea, neutrophilia, and leukocytosis. Initially transient and migratory, the rash became fixed, papular, and vesicular and showed minimal response to corticosteroids. Biopsy demonstrated sparse perivascular and interstitial dermal neutrophilic infiltrates, without vasculitis or significant dermal edema. Aggregates of neutrophils were found within and surrounding lymphangiectases. Biopsy of a new onset papule 3 weeks later demonstrated papillary dermal edema, denser neutrophilic infiltrate, and vasculitis-like changes. These 2 histopathologic patterns of ND, early and late, resemble neutrophilic urticarial dermatitis (also known as neutrophilic dermatitis with systemic inflammation) and Sweet syndrome, respectively. Extensive workup did not reveal evidence of relapsed chronic myelogenous leukemia, infection, or a coexisting systemic inflammatory disease. Dasatinib was discontinued and the eruption gradually resolved over 2.5 months. Still in molecular remission (no detectable BCR-ABL gene fusion), dasatinib therapy was recommenced at 3-month follow-up. After 10 months, she complains of malaise and arthralgia, but no cutaneous symptoms. The evolution and slow resolution of this ND in lipo-lymphedematous skin implicate poor lymphatic clearance of factors, antigenic and/or toxic, involved in the pathogenesis of ND.

The Jarisch-Herxheimer reaction (JHR) is a transient inflammatory syndrome triggered hours after the start of antibiotic treatment of spirochete infections, namely syphilis. Clinically, JHR manifests as an abrupt onset of constitutional symptoms and exacerbation of cutaneous lesions that resolve without intervention. JHR's pathogenesis is unclear and it is histopathologically rarely reported. Herein, the authors report a 47-year-old woman, with solitary erythema migrans and positive Lyme disease serology, who presented for medical care 14 days after commencement of doxycycline therapy. She complained of malaise, facial flushing, gingival erythema, and acquisition of additional plaques characterized by swelling, increased erythema, pruritus, and exfoliative scale. Punch biopsies demonstrated subacute to chronic spongiotic psoriasiform reaction patterns with a superficial lymphocytic infiltrate. By Borrelia-specific immunohistochemistry, spirochetes were found in the deep dermis, unassociated with inflammation, and focally in the upper spinous layer, associated with spongiosis. Borrelia burgdorferi DNA was detected by nested polymerase chain reaction. Doxycycline was discontinued, and symptoms and signs resolved within a few days. Liberation of endotoxin-like materials (eg, lipoproteins) from degenerating spirochetes and concomitant cytokine production is the suspected cause of JHR and supported by the finding of lesional spirochetes. Alternatively, a reversal reaction with a delayed-type hypersensitivity reaction is also a plausible cause based on spirochetes found in the lymphocytic spongiotic dermatitis.

Viral associated trichodysplasia spinulosa (VATS) is a rare cutaneous eruption characterized by folliculocentric papules, keratin spicules, and alopecia associated with trichodysplasia spinulosa-associated polyomavirus (TSPyV) infection. We report a case of a 6-year-old male child who presented with a generalized papular eruption during chemotherapy for acute lymphoblastic leukemia. The papules were tested for human papillomavirus (HPV) DNA by nested polymerase chain reaction (PCR) and TSPyV using PCR and gene sequencing studies. The lesions were positive for TSPyV by PCR combined with sequencing and showed high copy number with real-time PCR, and beta-papillomavirus was identified by PCR and sequencing. Immunohistochemistry revealed inner root sheath keratinocytes expressing nuclear HPV L1 capsid antigen. To our knowledge, this is the first case of concomitant productive HPV and TSPyV infection in a VATS-affected patient. The presence of HPV may be coincidental, however, further studies are needed to establish whether specific HPV genotypes influence the development of abnormal inner root sheath trichohyalin granules found in VATS.

Inflammatory and subcutaneous nodules can arise in treated and untreated cases of Whipple disease (WD). The inflammatory immune reconstitution syndrome describes paradoxical clinical inflammatory worsening of a preexisting condition because of a return of immune function. Clinicopathologic examination of 4 patients with WD who presented with erythema nodosum leprosum (ENL)-like lesions and the findings of a systematic review of this phenomenon revealed that ENL-like lesions occurred in predominantly middle-aged male patients who suffered from WD, mostly on the legs. Patients showed a nonvasculitic, mostly septal panniculits with neutrophils, macrophages, and lymphocytes. Numerous bacteria-laden periodic acid-Schiff + macrophages and free bacilli were detected in the dermis, as well as subcutaneous septae and adipose lobules. These lesions occurred in both untreated and treated patients as part of inflammatory immune reconstitution syndrome. In conclusion, ENL-like lesions represent a characteristic histopathologic pattern associated with WD, which can occur in different contexts whenever there is a change in the immunological status of the patient. This change can be triggered by antimicrobial treatment, immunomodulatory and immunosuppressant therapy, or occur spontaneously, rarely.

A minority of eyelid hidrocystomas are pigmented containing brown-black contents. Chromhidrosis describes the excretion of colored secretions composed of lipofuscin pigments in apocrine gland-rich anatomic locations. The objective of this study is to evaluate the clinicopathologic features of pigmented eyelid cysts. A case-control study was conducted, examining consecutive pigmented and nonpigmented eyelid hidrocystoma excision specimens. Over a 4-year period, 9 pigmented eyelid hidrocystomas were identified, representing 13% (9/70) of all hidrocystoma excisions. Compared to controls (n = 14), no difference existed for age [mean age 59 (44-78 years) vs. 60 (42-82 years)] or size [mean diameter 2.3 (1-4 mm) vs. 2.7 (1-5 mm)] (pigmented vs. nonpigmented, respectively), but a trend for female, left side, and lower lid predominance for pigmented hidrocystomas existed: 8:1 versus 7:7 F:M; 7:2 versus 7:7 left:right; 8:1 versus 9:5 lower:upper eyelid (pigmented vs. nonpigmented, respectively). Clinically, the pigmented cysts' color varied from dark blue, brown, and to black, and on gross examination, they expressed dark brown to black granular liquid contents. Applying histologic criteria of Jakobiec and Zakka, 8 of 9 and 14 of 14 pigmented and nonpigmented hidrocystomas were of apocrine type. Seven of 9 (78%) pigmented cysts and 6 of 14 (43%) nonpigmented hidrocystomas contained granular eosinophilic cyst contents and/or intracellular cytoplasmic granular pigmented deposits by light microscopy. (The pigmented cyst contents did not survive processing in 2 cases.) By histochemistry (periodic acid Schiff with diastase, Sudan Black, and Fite acid-fast positive staining) and ultraviolet fluorescence, these sediments were determined to be lipofuscin pigments. No hidrocystomas had melanin deposits, and one case had hemosiderin deposits in a scarred cyst wall in addition to cyst lipofuscin pigments. In studies of chromhidrosis, both normal and chromhidrotic apocrine glands contain lipofuscin pigments; the sole difference lies in the amount of lipofuscin granules. Similarly, for eyelid apocrine hidrocystomas, lipofuscin pigments exist in both groups. Presumptively, the amount of lipofuscin and degree of its oxidation distinguish pigmented from nonpigmented apocrine hidrocystomas.

Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal dominant disorder characterized by development of multiple adnexal cutaneous neoplasms including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. The syndrome of multiple familial trichoepitheliomas (MFT) is considered a phenotypic variant of BSS in which patients present with trichoepitheliomas only. We studied germline and somatic mutations of the CYLD gene by direct sequencing in patients with BSS (n = 49) and MFT (n = 18) using peripheral blood and 90 samples of frozen or formalin-fixed paraffin-embedded tumor tissue selected from 379 available histology specimens. Germline CYLD mutations were found in 51 patients (76%) from 36 families (75%). Germline CYLD mutations were found in 43 of the 49 patients with BSS (88%) but in only 8 of 18 MFT cohort (44%). Twenty-one frameshift, 15 nonsense, 3 missense, and 4 splice site mutations were found in patients with BSS, whereas 1 frameshift, 5 nonsense, and 2 splice site mutations were identified in the MFT cohort. Five novel mutations were identified including 4 frameshift mutations (c.1027dupA/p.T343NfsX7, c.2155dupA/p.M719NfsX5, c.2288-2289delTT/p.F763X, and c.2641delG/p.D881TfsX32) and 1 nonsense mutation (c.2713C>T/p. Q905X). Of the 76 tumors from 32 patients with a germline CYLD mutation, 12 were spiradenomas, 15 spiradenocylindromas, 26 cylindromas, 15 trichoepitheliomas, and 7 were other tumor types. Somatic mutations were detected in 67 specimens of these 76 tumors (88%). Of the 67 somatic mutations, 21 (31%) represented a sequence alteration and 46 (69%) showed loss of heterozygosity. In the remaining 9 cases (12%), the somatic changes remained unknown. A germline CYLD mutation was not detected in 14 tumor samples from 8 patients. In these 14 tumors, somatic mutations were identified in 6 samples (43%), all consisting of sequence alterations (1 sample showed 2 different sequence alterations). In the remaining 8 samples (53%), neither germline nor somatic mutations were found in the lesional tissue. Our study increases the catalog of known CYLD mutations in patients with BSS/MFT to 86 and documents the variability of somatic mutations that may occur in them. We confirm the absence of firm genotype-phenotype correlations and the existence of a subset of patients with BSS/MFT who lack a demonstrable germline CYLD mutation. Further studies are needed to explain the reasons for this phenomenon.

We report a new case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with extensive immunophenoptyping, genotyping (karyotype, array-comparative genomic hybridization, and fluorescent in situ hybridization), and long-term tumor cells culture. BPDCN is a very rare and aggressive disease clinically characterized by a skin revealing localization more or less rapidly disseminating to the bone marrow and other organs with or without and leukemia. The disease was initially phenotypically characterized by the expression of both CD4 and CD56 antigens, whereas lym- phoid and myeloid lineage antigens were negative. A phenotypic link with alpha-interferon (IFN-I)-producing plasmacytoid dendritic cells was demonstrated. The data collected in this case report provide additional biological and genotypical data on tumor cells of BPDCN. This study confirms the capability of tumor cells to secrete IFN-I, demonstrated by biological IFN-I activity of cultured cells and immunohistochemical expression of Mx-1 protein. Although a com- mon genetic profile involving chromosomes 5, 6, 9, 12, 13, and 15 has been identified, no specific genetic marker has been demon- strated that is specific to BPDCN. The demonstration of ETV6 gene deletion in this case deserves further investigations as a putative BPDCN marker.

Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

To the Editor:Recently, Kazakov et al1 performed a clinicopathologic and genotypic analysis on a series of 16 patients suffering from multiple (familial) trichoepitheliomas (MFT: MIM 601606) and found mutations in the CYLD gene in 46%. Based on the frequent presence of CYLD mutations in MFT, it, alo

To characterize the immunophenotype of inflammatory cells in lichen sclerosus (LS), we performed a comparative case control study using one- and two-color immunohistochemistry and the nitro blue tetrazolium (NBT) reaction. Study material consisted of 100 biopsies from patients with LS or from 12 control groups consisting of inflammatory, scarring, and depigmenting cutaneous disorders. In addition, fresh tissue was sampled from four vulvectomy specimens for NBT testing. The typical inflammatory infiltrate of LS contained numerous epidermotropic CD3+, CD8+, CD57+ cells, increased intraepidermal HLA-DR+ cells, and a dermal infiltrate rich in CD8+, CD57+, HLA-DR+, and CD68+ inflammatory cells. Comparing LS to the 12 control groups, epidermotropic CD57+ lymphocytes independently predicted LS (P = 0.006, logistic regression, multivariate analysis). Among the 12 control groups, only specimens of the inflammatory stage of morphea exhibited numerous dermal CD57+ lymphocytes. Two-color immunohistochemistry confirmed the CD3+/CD8+CD57+ and CD3+/ CD8+/CD57+HLA-DR+ epidermotropic and dermal lymphocytic phenotypes and the dermal macrophage CD68+HLA-DR+ phenotype. In LS, the NBT reaction revealed evidence of superoxide production associated with CD68+HLA-DR+ cells. Expansion of CD8+CD57+lymphocytes is associated with viral infections, autoimmune disease, malignancies, and transplantation and is suspected to be the result of chronic excessive antigen challenge. In these pathologic states, CD8+CD57+ lymphocytes (as terminally differentiated, antigen-specific T cells) participate in the suppression of cytolytic activity to limit tissue damage. In LS, activated macrophages and lymphocytes indicate persistent antigen-driven inflammation. LS's numerous CD8+CD57+ lymphocytes may be either the mediators or the consequence of its hallmark sclerosis.

Rheumatoid nodules, which affect the subcutis around joints, are the most frequent specific cutaneous lesions of rheumatoid arthritis (RA). Panniculitis is a rarely reported and nonspecific complication of RA. We report a 42-year-old woman with seropositive RA who presented with a 2-month history of lower leg panniculitis. Biopsy of a leg nodule showed a lobular neutrophilic infiltrate with lipophages and central basophilic necrosis. In addition, focal changes of lipomembranous fat necrosis indicative of ischemic damage were identified at the margins of the lobular infiltrate. Neutrophilic lobular panniculitis is commonly detected in panniculitis secondary to bacterial infections, pancreatitis, and factitial causes. However, this pattern of panniculitis has also been reported in some cases of erythema nodosum-like lesions found in Behçet disease or bowel bypass syndrome and in rare cases of seropositive RA. These reported histologic findings fall into the spectrum of neutrophilic vascular reactions described by Jorizzo and Daniels for RA-associated dermatoses. In view of these findings. RA and related neutrophilic dermatoses (e.g., Behçet disease) should be included in the differential diagnosis of neutrophilic lobular panniculitis.

Gadolinium (Gd) is associated with nephrogenic systemic fibrosis (NSF), a severe disorder mimicking scleroderma with involvement of the skin, lungs, heart, liver, and muscles. There is strong evidence that specific Gd-containing contrast agents (GCCAs) used in magnetic resonance imaging can cause NSF when administered to patients with chronic kidney disease. We present the 8-year history of cutaneous NSF with osseous metaplasia that occurred in a 56-year-old man with dialysis-dependent renal failure who was exposed to GCCA [gadopentate dimeglumine (Magnevist; Bayer Schering Pharma AG, Pittsburgh, PA)]. Three months after exposure to GCCA, he developed pruritic, pigmented patches that slowly coalesced and darkened over 8 years. Although not recognized at onset, skin biopsy showed typical histology of NSF affecting the entire dermis: CD34/procollagen I spindle cells associated with fibrosis. Biopsy performed 6 years later showed superficial scar-like fibrosis that was CD34/procollagen I and had numerous elastocollagenous balls (refractile elastic fibers surrounded by coarse collagen). Biopsy 7 years later showed the superimposition of osseous metaplasia on elastocollagenous balls. Both of these later biopsies had typical NSF histology affecting the deep dermis and subcutis. Over time, there was progressive diminishment of CD34 and procollagen I+ cells and an increase in FXIIIa+ and CD68 cells. Scanning electron microscopy and energy-dispersive x-ray spectroscopy showed Gd deposits in all areas of typical NSF histology but not in the regions of scar-like fibrosis, elastocollagenous balls, or osseous metaplasia. We suspect that the later changes may represent a late, involuting stage of NSF.

A broad and diverse spectrum of vasculitic syndromes exists. These syndromes affect the skin with varying levels of associated systemic manifestations, running the gamut from a self-limited, localized, cutaneous phenomenon to rapidly progressive, multiorgan disease. The majority of cases of cutaneous vasculitis will show a neutrophilic small vessel vasculitis that can be either a primary (idiopathic) disorder (eg, cutaneous leukocytoclastic angiitis) or a secondary disorder that is associated with drugs, infection (eg, streptococcal infection, viral hepatitis), or underlying disease (eg, connective tissue disease, malignancy). Biopsy is the gold standard for the diagnosis of cutaneous vasculitis and also necessary for the detection of cutaneous vascular immune complexes by direct immunofluorescence. Based on the type of vessel disrupted by inflammation (small and/or muscular), the distribution of vasculitis in the dermis and subcutis, and predominate inflammatory cell-type mediating vessel wall damage, a list of relevant differential diagnoses can be generated. This histologic information coupled with extravascular findings such as tissue eosinophilia, tissue neutrophilia, and/or granulomas, plus pathophysiologic markers such as direct immunofluorescent examination for immune complexes and serologic evaluation for antineutrophil cytoplasmic antibodies allows for more accurate diagnosis of specific vasculitic entities. Herein, we review both primary and secondary vasculitic syndromes that affect the skin and show a small vessel neutrophilic mediated vasculitis.

Sarcoidal granulomas are found in sarcoidosis and in reactions to foreign materials. We report the case of an 81-year-old woman with glaucoma who presented with multiple brown-black asymptomatic papules over the chin and involving nasal mucosa and columella of 1-year duration. Biopsy of the nasal mucosa and cutaneous papules showed sarcoidal granulomas associated with brown-black intracellular pigment within multinucleated giant cells. Electron-probe x-ray microanalysis demonstrated high sulfur content. Clinical studies showed no evidence of systemic sarcoidosis. Two of three ophthalmologic drops contained sodium bisulfite; bisulfite is known to cause allergic reactions. Although the exact substance causing the granulomatous reaction is unknown, the distribution of the lesions--nasal mucosa and columella (via the nasal lacrimal duct) and the underlying chin--implicate the eyedrops in the production of the pigmented granulomatous nodules.