Kaposi Sarcoma of the Nail Unit: A Case Report and Review of the Literature.

Introduction: Kaposi sarcoma is an angioproliferative neoplasm. Its manifestations are well known but nail involvement seems extremely underreported. Case Presentation: A 55-year-old man presented with a 6-month history of a growing subungual tumor affecting the third right toe. After surgical excision, histological examination revealed a Kaposi sarcoma. Discussion: We report a case of Kaposi sarcoma with nail involvement of only one toe as the first and unique manifestation, which is exceptional.

Nail Amyloidoma: Two Case Reports of a New Entity.

Introduction: Amyloidosis is a group of diseases characterized by extracellular deposits of abnormal insoluble proteins in different tissues. Amyloidoma is a localized tumoral deposit of amyloid in the absence of systemic amyloidosis, and it has been described in different anatomic sites. We report two cases of amyloidoma in the nail unit and provide insights into this recently described entity. Case Presentation: Both cases presented as an asymptomatic, slowly growing nodule underneath the distal nail bed of a toe with associated onycholysis. Histopathology was characterized in both patients by the presence of deposits of Congo red-positive, homogeneous, amorphous, and eosinophilic material within the dermis and subcutaneous tissue admixed with aggregates of plasma cells. In both cases, an extensive workup excluded systemic amyloidosis. Treatment was based on local excision, and no local recurrence or progression to systemic amyloidosis was observed at 1 year of follow-up. Conclusion: These are the first reports of amyloidomas of the nail unit. The clinical and histopathological presentations parallel those of an amyloidoma affecting the skin. Local excision seems to be an efficient treatment modality, but long-term follow-up is warranted in order to exclude recurrence, an associated marginal B-cell lymphoma, or progression to systemic amyloid L amyloidosis.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Histologic Patterns and Clues to Autoinflammatory Diseases in Children: What a Cutaneous Biopsy Can Tell Us.

Autoinflammation is defined by aberrant, antigen-independent activation of the innate immune signaling pathways. This leads to increased, pro-inflammatory cytokine expression and subsequent inflammation. In contrast, autoimmune and allergic diseases are antigen-directed immune responses from activation of the adaptive immune system. The innate and adaptive immune signaling pathways are closely interconnected. The group of 'complex multigenic diseases' are a result of mutual dysregulation of both the autoinflammatory and autoimmune physiologic components. In contrast, monogenic autoinflammatory syndromes (MAIS) result from single mutations and are exclusively autoinflammatory in their pathogenesis. Studying the clinical and histopathological findings for the various MAIS explains the phenotypical correlates of their specific mutations. This review aims to group the histopathologic clues for autoinflammation into three recognizable patterns. The presence of these histologic patterns in a pediatric patient with recurrent fevers and systemic inflammation should raise suspicion of an autoinflammatory component in MAIS, or, more frequently, in a complex multigenic disease. The three major histopathological patterns seen in autoinflammation are as follows: (i) the 'neutrophilic' pattern, seen in urticarial neutrophilic dermatosis, pustular psoriasis, aseptic neutrophilic folliculitis, and Sweet's syndrome; (ii) the 'vasculitic' pattern seen in small vessel-vasculitis (including hypersensitivity/leukocytoclastic vasculitis, thrombosing microangiopathy and lymphocytic vasculitis), and intermediate-sized vessel vasculitis, mimicking polyarteritis nodosa; and (iii) the 'granulomatous' pattern. Beyond these three patterns, there are additional histopathologic clues, which are detailed below. It is important for a dermatopathologist to recognize the patterns of autoinflammation, so that a diagnosis of MAIS or complex multigenic diseases may be obtained. Finally, careful histopathologic analyses could contribute to a better understanding of the various clinical manifestations of autoinflammation.

Subungual Solitary Angiokeratoma Simulating a Squamous Cell Carcinoma.

Subungual angiokeratoma is extremely rare. Only 1 case is reported in the literature, presenting as a longitudinal pigmented band on a toenail. We report a case of a subungual angiokeratoma on a fingernail of a 43-year-old woman, clinically mimicking a squamous cell carcinoma. Medical imaging revealed a soft tissue tumor and erosion of the distal phalanx. Although extremely rare, solitary angiokeratomas may arise in the nail apparatus and should be added to the differential diagnosis of subungual warty tumors.

Pseudoangiomatous xanthelasmoid mastocytosis: two case reports showing the hypervascularity of this rare variant of cutaneous mastocytosis.

Xanthelasmoid mastocytosis or xanthelasmoidea is a rare clinical variant of cutaneous mastocytosis characterized by a yellow hue of the clinical lesions, which are often misdiagnosed as juvenile xanthogranuloma. We present two pediatric cases of xanthelasmoid mastocytosis presenting as isolated mastocytomas, which are notable histopathologically for their hypervascularity. This pseudoangiomatous variant of cutaneous mastocytosis is important for pathologists to have knowledge of, so that a diagnosis of a vascular tumor is not rendered accidentally. The yellow hue has previously been explained by the usual deep and solid dermal mast cell infiltrate. In the two presented cases, however, the mast cell infiltrate was sparse, and the yellow color cannot be related to infiltrate density. We believe that the hypervascularity is at least one factor in the production of clinical xanthelasmoid appearance, and we propose the term 'pseudoangiomatous xanthelasmoid mastocytosis' to properly describe this rare variant of cutaneous mastocytosis.

Nail pathology.

When dealing with nails, pathologic examination is often indispensable to reach an accurate diagnosis. This requires a biopsy correctly performed by the dermatologist, a specimen correctly handled in the pathology lab, and a pathologist with good knowledge of the various nail conditions. The normal nail histology is first described in this paper. The pathologic aspects of melanocytic lesions, nonmelanocytic tumors of the nail apparatus, inflammatory nail conditions, and onychomycosis are then considered, together with their main differential diagnoses.

Eruptive tumors of the follicular infundibulum presenting as hypopigmented macules on the buttocks of two Black African males.

We report two cases of eruptive tumors of the follicular infundibulum (TFI) with an unusual clinical presentation which has not been described previously in literature. In both cases, the appearance was strikingly similar, consisting of multiple asymptomatic hypopigmented macules on the buttocks of two Black African males, aged 38 and 55 years old. In both cases, the eruption had evolved over several months. The individual lesions were of similar size, approximately 1 cm, with irregular and ill-defined borders. Histopathological examination revealed a superficial and horizontal plate-like proliferation of keratinocytes emanating from the epidermis with multiple slender attachments. Pale keratinocytes were present within the epithelial plates. A Fontana stain showed a loss of melanin pigment from the epithelial plates. Orcein (elastic) stain highlighted an increase of the number of the elastic fibers surrounding the tumor. On the basis of these findings, a diagnosis of eruptive TFI was established for both cases. Among the various presentations of TFI, only the eruptive variant appears to be clinically distinctive, with asymptomatic hypopigmented macules usually located on the face, neck and upper trunk. Eruptive TFI should also be added to the clinical differential diagnosis of multiple hypopigmented macules on the buttocks of Black patients.

Immunohistochemical study of 40 cases of longitudinal melanonychia.

The etiology of longitudinal melanonychia (LM) is difficult to establish by clinical and dermoscopic examinations alone. Microscopic examination of the nail matrix remains crucial. Two groups of LM may be identified: melanocytic activation (melanic pigmentation of the matrix epithelium without any increase in the density of melanocytes) and melanocytic proliferation (lentigo, nevus, or melanoma). The histological examination is challenging, and immunohistochemical investigations can be helpful. The objective of this study was to analyze the immunohistochemical findings with routinely used markers in melanocytic tumors-S-100 protein, HMB-45, and Melan-A-in LM. A series of 40 cases were analyzed: 10 activations, 4 lentigines, 7 nevi, 12 in situ melanomas, and 7 invasive melanomas. The sensitivity of S-100 protein is weak in benign and malignant intraepithelial melanocytes of the nail matrix, and if this marker is performed alone, it may be wrongly reassuring. However, the use of S-100 protein is essential to differentiate invasive melanoma, lacking an intraepithelial component, and particularly desmoplastic melanoma, from epithelial and mesenchymal tumors. HMB-45 and Melan-A are more sensitive than S-100 protein for the evaluation of intraepithelial melanocytic proliferation of the nail apparatus, with HMB-45 being the most intense marker. In the dermal component, HMB-45 and Melan-A were less sensitive than S-100 protein. In conclusion, we recommend that the panel of antibodies used for histological evaluation of LM should include HMB-45 and/or Melan-A and S-100 protein only if an invasive melanoma is suspected.

Cryopyrin-associated periodic syndrome: an autoinflammatory disease manifested as neutrophilic urticarial dermatosis with additional perieccrine involvement.

A female newborn presented with a congenital urticarial rash that consisted of fluctuating well-demarcated pink or pale reddish macules or slightly raised papules and plaques. In addition, purulent cerebrospinal fluid was present in the absence of evidence of congenital infection. Skin biopsy revealed a sparse infiltrate throughout the entire dermis, including the eccrine adventitia. The infiltrate was composed mostly of neutrophils, but rarely lymphocytes and eosinophils could also be seen. No vasculitis was present. Because of the presenting attributes, a diagnosis of cryopyrin-associated periodic syndrome (CAPS) was considered and the neonatal-onset multisystem inflammatory disorder (NOMID) that represents the most severe expression of the CAPS clinical spectrum was favored. Diagnosis was confirmed by identification of a mutation in the cold-induced autoinflammatory syndrome-1 gene and by an observed response to treatment with the interleukin-1 receptor antagonist anakinra. Both the clinical and histopathological findings of the presented case may represent a distinct entity within the spectrum of aseptic neutrophilic dermatitis. We refer to this spectrum as neutrophilic urticarial dermatosis (NUD), which may serve as a cutaneous marker of autoinflammation. NUD with perieccrine involvement should prompt consideration of CAPS, especially NOMID, in the context of neonatal multisystem disease.

Acantholytic tumor of the nail: acantholytic dyskeratotic acanthoma.

Acantholytic dyskeratotic acanthomas of the skin have been recently described in several publications. They differ from acantholytic acanthomas by the presence of dyskeratosis. However these tumors have never been described in nails. We report three cases localized on the thumb nail.

Congenital disseminated juvenile xanthogranuloma with unusual skin presentation and renal involvement.

We present a case of congenital juvenile xanthogranuloma (JXG) with both cutaneous and renal involvement. Skin lesions consisted of bluish papules and nodules (blueberry muffin baby) located on the head, trunk and proximal extremities. Subsequent investigations revealed a renal mass. Histopathology of both cutaneous and renal specimens was consistent with JXG. Both clinical presentation and extracutaneous localization were remarkable.

Cutaneous histopathological findings of Aicardi-Goutières syndrome, overlap with chilblain lupus.

We report a 2-year-old girl with developmental delay who, from the age of 1 year, developed perniotic lesions of the hands and feet initially diagnosed as chilblain lupus. Histological examination showed features of epidermal necrosis with intraepidermal bulla formation, interface dermatitis, lymphocytic vasculitis with fibrinoid necrosis and thrombi formation, both superficial and deep dermal lymphocytic infiltrate, lymphocytic eccrine hidradenitis and absence of marked dermal edema. Subsequent investigations suggested a clinical diagnosis of Aicardi-Goutières syndrome (AGS), a rare genetic leukoencephalopathy. Recently, both AGS and familial chilblain lupus, an autosomal dominant form of systemic lupus erythematosus (SLE), have been shown to be allelic thus suggesting a common pathogenic basis. In addition, a phenotypic overlap is apparent between SLE and AGS. To our knowledge, this is the first comprehensive dermatopathological report of the cutaneous lesions seen in AGS, and our paper highlights the importance of considering AGS in the differential diagnosis of perniosis and chilblain lupus.

Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice.

BACKGROUND: Demodicoses are thought to be rare, occurring mainly for patients with immunosuppression. OBJECTIVE: We sought to demonstrate the high frequency of demodicoses and the overlapping with papulopustular rosacea (PPR) . METHODS: We conducted a prospective epidemiologic study among 10 dermatologists. High Demodex density (Dd) was confirmed by standardized skin surface biopsy. RESULTS: In all, 4372 diagnoses, in which 115 were demodicoses, were collected among 3213 patients. Demodicosis was the 9th most frequent diagnosis (13th new). Each dermatologist observed an average of 2.4 demodicoses a week (1.2 new). The proportion of demodicoses varied greatly according to the dermatologist. The general status was good in 110 patients; only 3 had known immunodeficiency. The most frequent symptoms were follicular scales (71%) and telangiectasia (63%). The mean Dd was higher in pityriasis folliculorum (m = 61 D/cm 2 ) than in PPR (m = 36 D/cm 2 ; P = .04); 42 patients with PPR had a high Dd, 6 had a low Dd. CONCLUSION: Demodicoses are frequent and occur among patients who are immunocompetent. PPR with normal Dd are rare.

POEMS syndrome revealed by multiple glomeruloid angiomas.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin disorders) is a rare multisystemic disease associated with plasma cell dyscrasia. A 68-year-old woman with chronic renal insufficiency and arterial hypertension included in her medical history was admitted to the hospital with confusion, somnolence and asthenia. She presented ascites, hepatosplenomegaly, leg oedema, distal dysesthesias, leuconychia and multiple nodular purple red angiomas on the trunk, upper limbs and fingers. Hypothyroidism was revealed in the laboratory investigations and monoclonal IgG peak in immunoelectrophoresis. Electromyography showed both demyelinisating and axonal degenerative neuropathy. The diagnosis of POEMS syndrome was based on the dermatopathological examination of a cutaneous angioma; histology revealed features of glomeruloid angioma, a specific marker of this syndrome.