TEMPI syndrome: A clinical, light-microscopic and phenotypic evaluation with review of the literature.

BACKGROUND AND OBJECTIVES: TEMPI (telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonaryshunting) syndrome is a rare multisystemic disease classified as a monoclonal gammopathy of cutaneous significance. The pathogenesis and etiology of TEMPIare not well known because of the rarity of this disorder. Although telangiectasias are the hallmark of this syndrome, skin biopsies are rarely performed. We aim to further characterize TEMPI syndrome through the evaluationof a skin biopsy. METHODS: We reviewed the histopathology and immunophenotypic profile of a skin biopsy from a 53-year-oldwoman diagnosed with TEMPI syndrome. Other components of her syndromic complex included an IgA myeloma, elevated vascular endothelial growth factor (VEGF), and erythrocytosis. RESULTS: A biopsy showed prominent vascular ectasia with some degree of microvascular basement membranezone thickening. Our patient had a reduction in neoplastic plasma cell burdenand clearing of her telangiectasias following myeloma directed treatment. CONCLUSIONS: TEMPI can beviewed as a reactive vascular paraneoplastic syndrome in the setting of a plasma cell dyscrasia. Elaboration of VEGF from neoplastic plasma cells is likely pathogenetically implicated and appears to be a common link that explains other vascular lesions associated with monoclonal gammopathy syndromes.

Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Linear IgA bullous dermatosis in the setting of angioimmunoblastic T-cell lymphoma.

We report an 80-year-old male developing linear IgA bullous dermatosis (LAD) in the setting of angioimmunoblastic T-cell lymphoma (AITL). This phenomenon is rare, as only three cases have been described in the literature. The pathophysiologic process can be attributed to dysregulation in somatic hypermutation and the expression of chemokine receptor 5 in AITL, contributing to increased IgA. Immunoglobulin production resulting from clonal plasma cell expansion may be because of the B-cell promotional effect by neoplastic follicular helper T-cells. Beyond providing a pathophysiologic platform for AITL-associated LAD, we also briefly summarized prior cases. This report demonstrates the importance of considering LAD in the differential diagnosis for patients with a bullous eruption in the setting of AITL.

Primary cutaneous blastic marginal zone lymphoma: A comprehensive clinical, light microscopic, phenotypic and cytogenetic appraisal.

BACKGROUND: Primary cutaneous marginal zone lymphoma (PCMZL) is a form of indolent lymphoproliferative disease where the disease is largely a cutaneous confined process. It is typically a neoplasm composed of post germinal small B-cells and light chain restricted plasma cells in a background of reactive T-cell hyperplasia and benign germinal centers. Rarely a significant degree of large cell infiltration occurs warranting the categorization as blastic marginal zone lymphoma. MATERIALS AND METHODS: We reviewed our data base over a time period of 2016 to 2022 for cases diagnosed as blastic MZL. Twelve cases were identified. The clinical records and pathological data were reviewed. RESULTS: Nine of the cases represented de novo forms of blastic MZL while in three cases there was a prior history of MZL. Multifocal cutaneous disease was not uncommon and one quarter of the cases had evidence of extracutaneous dissemination. All patients except three achieved remission with varied therapeutic interventions depending on the extent of the disease ranging from conservative re-excision to chemotherapy. No patient died from lymphoma. Light microscopically, there was evidence of a background of conventional MZL in the majority of cases. The large cell component was typically characterized by multiple micronodular aggregates throughout the dermis although in three cases there was a striking diffuse large cell component as the dominant infiltrate. Phenotypically, a third of the cases showed either CD5 or CD23 positivity amidst neoplastic B cells. Significant staining for BCL-2 was noted in the majority of cases tested while extensive MUM-1 positivity was observed in half of the cases tested. Kappa or lambda light chain restriction was seen in most. The Ki67 proliferation index exceeded 30 % in all cases. There was C-MYC positivity in two cases. While most cases did not detect cytogenetic abnormalities, one case had multiple cytogenetic hits that are associated with diffuse large B cell lymphoma. Next generation sequencing showed a Ten-eleven translocation 2 mutation in the earlier biopsy prior to transformation and in the later biopsy after transformation along with an additional B2M mutation in the transformed biopsy. Both types of mutations are very uncommon but held to contribute to tumor progression in the setting of diffuse large B cell lymphoma. CONCLUSION: Blastic MZL is associated with a more aggressive clinical course. Even when there is disseminated disease patients while not always cured did not have a fatal course in this series. The light microscopic findings are reproducible. The background of MZL, identification of larger cells in significant numbers without a follicle center phenotype, at times expressing CD5 or CD23 with variable positivity for MUM1, BCL-2 and C-MYC and a high proliferation index define the pathology in most. Certain cytogenetic abnormalities and genetic mutations implicated in large cell transformation into a diffuse large B cell lymphoma are seen in blastic MZL with earlier biopsies prior to transformation potentially harboring at risk genetic mutations.

Lichen sclerosus: A C5B-9 mediated chronic microvascular injury syndrome potentially reflective of common adult comorbidities.

Lichen sclerosus (LS) is a cutaneous disease of unknown etiology that often involves the vulva or foreskin but also can affect extragenital sites. Regardless of the anatomic site, the histomorphology and presumably pathogenesis are similar. Perhaps a clue to the pathophysiology of LS lies in its frequent association with morphea, specifically, when occurring in an extragenital context. In our experience a striking feature evident in established lichen sclerosis (LS) is one of superficial vascular drop out whereby residual vessels exhibited endothelial cell necrosis and microvascular basement membrane zone thickening, the latter reflective of antecedent episodes of microvascular injury. We sought to understand the pathophysiology that underlies the distinct vascular changes and in doing so, shed light on the pathogenesis of LS. We examined 44 cases of LS over a period of 2019 to 2021. We were able to obtain past medical histories in 34 of the 44 cases. Regarding pathological assessment, the predominant focus was on microvascular changes. We assessed the role of C5b-9 mediated vascular injury in the pathogenesis of the vasculopathy and enhanced type I interferon signaling in vessels given the morphologic semblance to the select interferonopathy syndromes, namely fibrosing dermatomyositis and Kohlmeier Degos disease. We examined the expression of CMV DNA and protein based on prior observations in an earlier study that isolated early protein expression in the microvasculature in the setting of LS and scleroderma. From a clinical perspective, the most striking association was an older age at the time of diagnosis (mean age of 62 years and median age of 61.5 years) and the presence of vascular comorbidities of diabetes, hypertension, and hyperlipidemia in almost 80% of cases. All cases showed significant microvascular changes in the superficial corium with the most frequent findings being those of significant basement membrane zone reduplication and vascular drop out. A number of cases showed prominent microvascular deposits of C5b-9 in the zone of hyalinizing fibrosis or subjacent to the discernible table of fibroplasia in the absence of enhanced type I interferon signaling. In no case were there viral cytopathic changes associated with CMV affecting the endothelium. The studies that encode CMV DNA or protein did not show a significant role for CMV reactivation in endothelium in the majority of the studied cases. It is concluded that the pathophysiology of LS includes a microvascular injury syndrome within the papillary dermis. The mechanism of endothelial cell injury is complement mediated at least in part and could reflect an adaptive immune response targeting endothelium indicative of classic complement pathway activation when coexisting with morphea or occurring in younger individuals. A non-immune based endothelial dysfunction and complement mediated injury unrelated to antibody driven classic complement pathway activation are more likely pathogenetically in the setting of certain diseases like diabetes mellitus and hypertension. Vascular drop out can be explained by the diminished endothelial progenitor pool needed to repopulate the damaged microvessels in certain settings like hypertension and diabetes.

Cutaneous type IV hypersensitivity reaction following tebentafusp treatment for uveal melanoma.

Tebentafusp is a bispecific protein that recently underwent FDA approval for the treatment of metastatic uveal melanoma that functions by redirecting cytotoxic T cells to glycoprotein-100, a protein highly expressed in melanoma. Although clinical trials have demonstrated that rashes are common in the first few days of treatment, little is known about skin reactions that develop later in the treatment course. Herein, we describe a type IV hypersensitivity reaction and vitiligo-like depigmentation that developed six weeks into treatment and discuss the possible mechanisms underlying these reactions. The type IV hypersensitivity reaction resolved without intervention within seven weeks of onset, suggesting that tebentafusp can be safely continued in select patients who develop this cutaneous reaction.

Cutaneous collagenous vasculopathy: A report of three cases.

Cutaneous collagenous vasculopathy is a rare pauci-inflammatory, superficial, cutaneous vasculopathy characterized by progressive fine-branching telangiectasias clinically, while light microscopically one observes dilated venules and capillaries within the superficial dermis exhibiting excessive Type IV collagen within the vessel wall. We present three cases of collagenous vasculopathy. Two cases were associated with certain autoimmune stigmata, including a positive serologic anti-endothelial cell antibody assay and positive lupus anticoagulant in one, while the third case had positive anti-ribonucleoprotein (RNP) antibodies. The latter case was associated with chronic hydroxyurea therapy for an underlying myeloproliferative disorder. We explore the role of immune- and non-immune-based endothelial cell injury in the pathogenesis of collagenous vasculopathy.

Idiopathic systemic capillary leak syndrome, a unique complement and interferon mediated endotheliopathy syndrome: The role of the normal skin biopsy in establishing the diagnosis and elucidating pathogenetic mechanisms.

Idiopathic Systemic Capillary Leak Syndrome (ISCLS), also known as Clarkson's Syndrome, is due to primary fluid and protein leak across capillaries that leads to an accumulation of interstitial fluids and cardiovascular collapse from intravascular hypovolemia. Viral infections are a putative trigger of these episodes. ISCLS is typically associated with a monoclonal gammopathy. Here we present four patients with idiopathic systemic capillary leak syndrome. The cohort consists of three men and one woman who range in age from 55 to 72 years old. All of the patients had a monoclonal gammopathy. Two patients had viral triggers. Biopsies of normal skin were examined throughout all phases of the disease. During an acute attack, we identified perivascular mixed CD4+ and CD8+ T cell lymphocytic infiltrates in the superficial dermis. We observed significant microvascular deposits of C5b-9 and upregulation of type I interferon signaling in endothelium along with reduced serum levels of complement during very active disease. We also identified deposits of immunoglobulin along the dermal epidermal junction mirroring the monoclonal immunoglobulin isotype implicated in each patient. During a post treatment recovery or mild disease phase there was reduced inflammation and decreased amounts of C5b-9 and type I interferon expression. Sudden onset capillary leak syndrome reflects enhanced endothelial cell permeability as a unique form of endothelial injury mediated by the combined effects of complement pathway activation and upregulation of type I interferon signaling on endothelium.

A Covid-19 Patient with Complement-Mediated Coagulopathy and Severe Thrombosis.

We report a patient with severe Covid-19-associated coagulopathy and type 2 diabetes mellitus who tested positive for antiphospholipid antibodies (aPL). Analysis of skin specimens suggested direct SARS-CoV-2 viral-induced and complement-mediated vascular injury and thrombosis, consistent with prior reports. Serial aPL testing demonstrated high levels of anticardiolipin antibodies (aCL) that declined to insignificant levels over a period of 5 weeks. SARS-CoV-2 RNA was detected in nasopharyngeal swab specimens on serial assays performed over the same 5-week period, though it was not detected thereafter. We hypothesize that SARS-CoV-2 viral-induced aPL contributed to severe Covid-19-associated coagulopathy in this patient.

CD8+ Lymphogranulomatous Dermatitis as a Manifestation of Malignancy-Associated Immunodeficiency: Rethinking Paraneoplastic Granulomas.

ABSTRACT: Paraneoplastic granulomatous disease occurs in approximately 7.3% of patients with non-Hodgkin lymphoma, most commonly among patients with chronic lymphocytic leukemia (CLL). These lesions are often reported to appear similar to sarcoidosis in clinical presentation and under light microscopy. However, comprehensive descriptions of the cytomorphologic characteristics of these paraneoplastic granulomas are lacking, and the mechanisms involved in their formation remain ill-defined. Noninfectious dermal granulomatous reactions have also been reported in many primary immunodeficiencies, including common variable immune deficiency and ataxia-telangiectasia. We present a case of noninfectious CD8+ predominant granulomatous dermatitis with ocular involvement occurring in the setting of CLL and marked hypogammaglobulinemia. Based on the analysis of shared factors in patients with primary immunodeficiencies and CLL, we conclude that the presence of pan-humoral immunodeficiency could itself be a risk factor for developing a CD8+ lymphogranulomatous reaction. This report and associated discussion evince that CD8+ predominant granulomatous reactions, distinct from sarcoidosis, may represent a previously unappreciated segment of the paraneoplastic granulomas observed in hematologic malignancies.

A newly described cutaneous reaction at sites of insulin pump use in a child with Type 1 diabetes.

Continuous subcutaneous insulin infusion (CSII), or insulin pumps, with or without continuous glucose monitoring (CGM) devices have become the standard of care for patients with type 1 diabetes. While increasingly popular, a wide range of reported skin reactions to CSII and CGM devices was found. We present this case of a pyogenic granuloma-like neutrophilic and granulomatous response to an insulin pump to increase awareness of a previously uncharacterized cutaneous adverse reaction at insulin pump infusion sites.

Severe COVID-19: A multifaceted viral vasculopathy syndrome.

The objective of this study was to elucidate the pathophysiology that underlies severe COVID-19 by assessing the histopathology and the in situ detection of infectious SARS-CoV-2 and viral capsid proteins along with the cellular target(s) and host response from twelve autopsies. There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3. Importantly, this microvasculitis was associated with characteristic findings on hematoxylin and eosin examination that included endothelial degeneration and resultant basement membrane zone disruption and reduplication. It is concluded that serious COVID-19 infection has two distinct mechanisms: 1) a microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and 2) the pseudovirions dock on ACE2+ endothelial cells most prevalent in the skin/subcutaneous fat and brain that activates the complement pathway/coagulation cascade resulting in a systemic procoagulant state as well as the expression of cytokines that produce the cytokine storm. The data predicts a favorable response to therapies based on either removal of circulating viral proteins and/or blunting of the endothelial-induced response.

Anti-complement C5 therapy with eculizumab in three cases of critical COVID-19.

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19.

Juvenile dermatomyositis resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination of cyclophosphamide and rituximab: case-based review.

Dermatomyositis (DM) is a multi-system disease that results in chronic inflammation principally of the skin and striated muscle. Small blood vessel injury in the GI tract has been described in dermatomyositis, manifesting as bleeding, ulceration, pneumatosis intestinalis, and ultimately perforation. Recent histopathological studies have shown deposits in the capillaries of the skin, gastrointestinal tract, and brain of patients with dermatomyositis similar to that found in patients with Degos disease, suggesting these disease processes are closely related or represent varying degrees of severity on the same pathologic spectrum. We report a case of juvenile dermatomyositis (JDM) resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination rituximab and cyclophosphamide therapy. We systematically reviewed the literature detailing the medical and surgical treatments for gastrointestinal perforation in dermatomyositis, Degos-like dermatomyositis, and Degos disease. In addition to our case, as of October 2019, we identified 36 cases describing gastrointestinal perforation in patients with underlying dermatomyositis, 5 cases of Degos-like dermatomyositis and 17 cases of idiopathic Degos disease. Corticosteroid therapy was used widely for dermatomyositis and Degos-like dermatomyositis, while antiplatelet and anticoagulant medications were chiefly used for patients with idiopathic Degos disease. However, there were no cases that detailed the successful treatment of dermatomyositis or Degos disease with gastrointestinal perforation with rituximab alone or combined with cyclophosphamide. We report that rituximab, in combination with cyclophosphamide, can be used as a novel adjunctive therapy to successfully treat dermatomyositis with Degos-like gastrointestinal perforation.

Solitary congenital Langerhans cell histiocytoma: A pattern of benign, spontaneous regression in patients with single lesion disease.

Langerhans cell histiocytosis (LCH) is the neoplastic proliferation of dendritic langerin-positive histiocytes manifesting as either single system unifocal, single system multifocal, or multisystem disease. The designation Hashimoto-Pritzker, or self-healing LCH, has fallen out of favor since it is impossible to predict at time of diagnosis whether the disease is truly self-remitting or capable of spreading to other organ systems. We review the English literature on solitary congenital Langerhans cell histiocytoma, draw novel conclusions from the data provided by 81 cases in the literature, and illustrate a typical presentation of the diagnosis with a previously unreported patient. Each of the patients diagnosed with solitary congenital histiocytoma experienced spontaneous resolution and had no signs of systemic disease at latest follow-up. Furthermore, we offer an analysis of the histopathological findings available from the 81 cases and our patient. Based on our study observations, we propose solitary congenital Langerhans cell histiocytoma may portend a good prognosis and represent a distinct entity. However, until further confirmation with prospective studies, we recommend clinicians continue conducting appropriate workup to rule out systemic involvement.

Analysis of complement deposition and viral RNA in placentas of COVID-19 patients.

COVID-19, the disease caused by the novel Coronavirus, SARS-CoV-2, is increasingly being recognized as a systemic thrombotic and microvascular injury syndrome that may have its roots in complement activation. We had the opportunity to study the placental pathology of five full-term births to COVID-19 patients. All five exhibited histology indicative of fetal vascular malperfusion characterized by focal avascular villi and thrombi in larger fetal vessels. Vascular complement deposition in the placentas was not abnormal, and staining for viral RNA and viral spike protein was negative. While all cases resulted in healthy, term deliveries, these findings indicate the systemic nature of COVID-19 infection. The finding of vascular thrombosis without complement deposition may reflect the systemic nature of COVID-19's procoagulant effects unrelated to systemic complement activation.

Lacrimal tissue resection in Fasanella Servat operation and the correlation to dry eye.

Purpose: Fasanella-Servat operation (FSO) was previously reported to be associated with post-operative dry eyes due to accessory lacrimal gland resection during the surgery.We performed a retrospective, cohort study to determine the frequency of lacrimal tissue resection during FSO and its correlation with post-operative eye dryness and keratopathy.Methods: Review of all patients who underwent FSO at New York-Presbyterian Weill Cornell Hospital over a two-year period (2013-2015). Patients were included only if they had adequate histopathological specimens of the resected tissue obtained during surgery. Outcomes included the study of the pathological specimen for the presence of lacrimal tissue; Post-operative dry eye symptoms and pre- and post-operative corneal epitheliopathy.Results: 46 patients with a total of 58 eyelid resections were studied.Eight eyelids (13.7%) were found to have lacrimal tissue present in the pathology specimens.Postoperatively, nine patients reported some symptoms of dry eye and new-onset keratopathy was noted in four eyes (6.8%), only one of which had lacrimal tissue present in histopathology specimen obtained from surgery.Discussion: Previous studies found lacrimal tissue present in up to 43% of specimens resected during FSO. Our data found a lower rate of lacrimal tissue resection during FSO, and did not find an association between lacrimal tissue resection and post-operative dryness or epitheliopathy.Conclusion: Our study is one of few to examine histopathological resections from the FSO.We found that lacrimal tissue is not frequently resected during FSO, and when it is resected, there is no increased incidence of post-operative dryness or keratopathy.

Protean Neurologic Manifestations of Two Rare Dermatologic Disorders: Sweet Disease and Localized Craniofacial Scleroderma.

PURPOSE OF REVIEW: To describe diverse neurologic and neuroradiologic presentations of two rare, immunologically mediated skin conditions: Sweet disease and localized scleroderma (morphea). RECENT FINDINGS: Core syndromes of neuro-Sweet disease (NSD) are steroid responsiveness, recurrent meningitis, and encephalitis. Focal neurologic, neuro-vascular, and neuro-ophthalmologic syndromes have been reported recently in NSD. A variety of steroid-sparing treatments and biologics have been used for relapsing NSD. Localized craniofacial scleroderma is associated with seizures, headaches, and, less commonly, focal deficits and cognitive decline. Immunosuppressive therapy may be required in patients with disease progression; some refractory cases have responded to IL-6 inhibition. Our review provides an up-to-date reference for neurologists faced with a patient with a history or skin findings consistent with Sweet disease or localized scleroderma. We hope that it will stimulate collaborative studies aimed at unraveling the pathogenesis of these disorders, better characterization of their neurologic manifestations, and discovery of optimal therapeutic solutions.

Amyloid-Associated Alopecia: A Reappraisal Including Its Pathophysiology.

Primary systemic amyloidosis has a varied clinical presentation, making it one of the great masqueraders of other disease entities in clinical medicine. The association of amyloidosis with alopecia is uncommon with at least 22 cases reported in the literature mostly in the setting of systemic amyloidosis. Alopecia in these patients occurs either as the initial presentation of the systemic amyloidosis or it happens during the disease course. The occurrence of amyloid alopecia associated with light chain (LC) restricted plasmacytic infiltrates in the absence of systemic amyloidosis, however, it is not well known. We report 3 cases of LC-associated amyloidosis presenting with alopecia, whereby there was evidence of a systemic plasma cell dyscrasia in 2 of the patients, one of whom developed multiple myeloma. None of the patients had systemic amyloidosis. Skin presentation in the patient with multiple myeloma was characterized by a diffuse form of alopecia affecting the entire scalp, eyebrow, and axillary and pubic hair in contrast to the localized form of alopecia noted in the other 2 patients. The mechanism by which LC-associated amyloidosis eventuates in this pattern of nonscarring alopecia potentially reflects the affinity of this form of amyloid for dermatan sulfate. Dermatan sulfate is found at highest concentrations within the adventitial dermis of the superficial to mid isthmic portions of the anagen hair follicles likely interfering with the hair cycle and induces early hair follicle involution. The result is a pattern of alopecia that can clinically and to some extent pathologically resemble either androgenetic alopecia or alopecia areata.

Spontaneous Hair Repigmentation in an 80-Year-Old Man: A Case of Melanoma-Associated Hair Repigmentation and Review of the Literature.

Spontaneous hair repigmentation of physiologically white or gray hair is a rare occurrence that may be associated with melanoma in elderly individuals. We present the first case of this phenomenon in a man. A gray-haired, 80-year-old man presented to dermatology clinic with a 3-cm lock of black hair on his vertex scalp that developed over 1 year. Punch biopsies showed an increase in junctional dendritic melanocytes with rare pagetoid cells and extension along the follicular outer root sheath epithelium and interfollicular epidermis, associated with prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs. Although the findings on the biopsies were not diagnostic of melanoma in situ, an irregular interfollicular distribution of melanocytes was concerning for an adjacent atypical process. A complete excision was performed and revealed melanoma in situ, lentigo maligna type. Rare reports describe spontaneous hair repigmentation as a harbinger of lentigo maligna in women. Repigmentation can occur in the setting of proliferation of malignant pigment-producing melanocytes or by paracrine stimulation of benign bulbar melanocytes through receptor tyrosine kinase KIT activation. Presence of prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs in our patient's biopsies was suggestive of paracrine or physiologic stimulation of bulbar melanocytes. Given the importance of early melanoma detection and the low visibility of the scalp, this report raises awareness of an extraordinary presentation of lentigo maligna and exemplifies the importance of close clinicopathologic correlation to ensure optimal clinical management and patient outcome.