Papulonodular mucinosis in a patient with systemic lupus erythematosus and antiphospholipid syndrome.

The skin is one of the target organs most commonly affected in lupus erythematosus (LE) and a wide range of cutaneous changes have been described in LE patients. Papulonodular mucinosis (PNM) in particular is an uncommon cutaneous manifestation of LE. We discuss the case of a 26-year-old Senegalese woman with systemic LE and antiphospholipid syndrome (APS) who presented with pruritic papules on her back and extremities that appeared when she was on vacation in Africa and non-compliant with medications. Histopathologic examination was consistent with PNM. The patient was treated with mycophenolate mofetil and hydroxychloroquine, with subjective relief in pruritis at 6-week follow-up. To our knowledge, this is the first case of PNM presenting in a patient with both SLE and APS. Whether APS contributes to the pathogenesis of PNM is currently unknown.

Spiny keratoderma.

We present a case of a 48-year-old man with an approximately 30-year history of spiny projections on the palms, which were histopathologically consistent with spiny keratoderma. Spiny keratoderma is a rare entity of unknown etiology that has been described with both hereditary and acquired variants. The hereditary form, which is most likely the diagnosis in our patient, manifests at a younger age and is benign. The acquired variant, which presents in older adults, has been associated with a variety of systemic diseases and malignant conditions. In patients suspected of having acquired spiny keratoderma, an evaluation for malignant conditions may be warranted.

Primary localized cutaneous amyloidosis.

A 61-year-old man presented for evaluation of a bruise-like lesion of the right knee. He was found to have an ill-defined, light brown patch with focal areas of dark red and brown. The histopathologic diagnosis was consistent with amyloidosis. Further subtyping showed that the amyloid protein was AL (κ). A systemic evaluation failed to show internal involvement. Amyloidosis comprises a spectrum of diseases, which range from systemic to localized cutaneous types, and is characterized by the extracellular deposition of amyloidosis protein as beta-pleated sheets. The forms of amyloidosis are differentiated by the specific types of protein-derived amyloidosis fibers. Both nodular and primary systemic amyloidosis can present as nodules on the skin owing to deposition of AL type amyloid protein. Primary systemic amyloidosis, which carries a poorer prognosis than does nodular amyloidosis, also may give rise to ecchymoses and many other cutaneous and extracutaneous findings. Histopathologic features are similar in both cases and involve the deposition of amorphous, eosinophilic material in the dermis. Nodular amyloidosis may progress to primary systemic disease in up to 50% of cases. Because our patient had no systemic involvement and the lesions did not appear nodular in nature, the patient was given a diagnosis of primary localized AL cutaneous amyloidosis. Routine follow-up for this patient is necessary to detect any potential disease progression.

Trauma-related papular granuloma annular.

Granuloma annulare (GA) is a benign, granulomatous disease with several clinical manifestations, which include localized, generalized, perforating, subcutaneous, patch, papular, and linear forms. We report a case of papular GA of the dorsal aspects of the hands that arose after repeated, direct trauma to the site of subsequent involvement. Although multiple etiologies for GA have been proposed, which include ultraviolet light, arthropod bites, trauma, tuberculin skin tests, viral infections, and PUVA photochemotherapy, the underlying pathogenesis of the disorder remains unclear. However, owing to the key histopathologic findings of focal collagen and elastic fiber degeneration and mucin deosition in GA, it is not surprising that cutaneous trauma may have played a role in connective tissue injury, subsequent degeneration, and the production of a granulomatous response with increased mucin deposition.

Livedo reticularis.

Livedo reticularis (LR) is a net-like, violaceous, hyperpigmented pattern on the skin that reflects an underlying change in cutaneous blood flow. The causes of LR are many and most commonly include connective tissue diseases, vasculitis, hypercoagulability, and embolic events. We describe a 49-year-old man who presented with painful LR and ulcers on the lower extremities as a manifestation of chronic natural killer cell leukemia (CNKL). There have been only a few cases previously reported in the literature. We report an additional case of a patient with both LR and CNKL and suggest a possible mechanism that explains this association.

Necrolytic acral erythema.

Necrolytic acral erythema is a rare, cutaneous manifestation of hepatitis C virus infection that is characterized by erythematous, violaceous or dusky papules, blisters, and/or erosions in the early stages and by well-demarcated, hyperkeratotic, targetoid plaques with a peripheral rim of macular erythema, secondary lichenification and hyperpigmentation, and overlying fine micaceous or necrotic-appearing scale in the later stages. Because most topical modalities prove ineffective, treatment of the underlying viral infection or therapeutic zinc supplementation are required for clinical improvement.

Fluoroscopy-associated radiation dermatitis.

We present a 67-year-old man with an ulcerated, indurated plaque on the right mid back with a presumed diagnosis of morphea that was complicated by an allergic contact dermatitis. Further clinical and histopathologic data elucidated the diagnosis of fluoroscopy-induced radiation dermatitis. We present a brief review of the common locations, clinical characteristics, pathophysiology, and management options for fluoroscopy-induced radiation dermatitis.

Steatocystoma.

Steatocystoma multiplex is a rare condition that is characterized by cutaneous cysts and may be inherited in an autosomal dominant manner or may occur sporadically. The pathogenesis is hypothesized to involve mutations in the keratin 17 gene. There are no internal manifestations. The lesions are usually asymptomatic. However, a suppurative variant exists in which the lesions become inflamed and suppurative after minor trauma. Treatments include cryosurgery, aspiration, surgical excision, laser therapy, and modified surgical incision techniques. This report presents a case of steatocystoma multiplex, the suppurative variant, in a 26-year-old woman with involvement of rare locations on the buttocks, groin, and extremities.

Syringocystadenoma.

We present a case of a 35-year-old woman with a yellow, verrucous, and itchy plaque on her scalp. Within this plaque, there was an erythematous, bleeding papule. Histopathologic findings were compatible with a diagnosis of syringocystadenoma papilliferum within a nevus sebaceous. We present a brief review of the natural history of nevus sebaceus, its pathogenesis, and management.

Granulomatous dermatitis related to silicone implant.

Silicone in liquid and gel implantation may induce granuloma formation and migration. Although there are many complications associated with solid silicone implantation, there have been no published reports of distant granuloma formation. We present a case of a woman with clinical and serologic findings that are consistent with systemic lupus erythematosus and a histopathologic diagnosis of foreign body granulomatous dermatitis 20 years after solid silicone nasal implantation. We review the literature on silicone granulomas and their treatment and speculate on the potential etiologies of a challenging case presentation.

Evaluation of ocular blood flow in the assessment of symptomatic carotid stenosis.

BACKGROUND AND PURPOSE: The degree of internal carotid artery (ICA) stenosis determined by criteria from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) is not the most accurate index to assess distal flow compromise. Distal ICA perfusion is also determined by factors such as tandem carotid stenosis and collateral circulation. Quantification of end-organ ocular perfusion using non-invasive laser speckle flowgraphy (LSFG) may provide insights into distal ICA flow. This study prospectively assessed the degree of ICA flow using LSFG. METHODS: Eighteen patients with symptomatic carotid stenosis underwent LSFG evaluation. LSFG was used to extract ocular blood flow metrics recorded simultaneously in the retina, choroid, and optic nerve head. The following ocular flow parameters were measured with LSFG: mean blur rate (MBR), flow acceleration index (FAI), and rising rate (RR). Syngo iFlow perfusion imaging was used to objectively quantify contrast flow in the ICA and brain parenchyma during digital subtraction angiography. Time to peak (TTP) and contrast delay were extracted from seven different regions of interest (ROIs). RESULTS: MBR, FAI, and RR were correlated with NASCET degree of stenosis. FAI and RR also improved after stenting. TTP improved after stenting in three ROIs. A moderate negative correlation was observed between FAI and contrast delay. CONCLUSIONS: LSFG non-invasively quantifies end-organ blood flow distal to the ICA origin. LSFG metrics have the potential to quantify end-organ perfusion and determine if a proximal carotid stenosis is symptomatic.

Evaluating the effect of acute diesel exhaust particle exposure on P-glycoprotein efflux transporter in the blood-brain barrier co-cultured with microglia.

A growing public health concern, chronic Diesel Exhaust Particle (DEP) exposure is a heavy risk factor for the development of neurodegenerative diseases like Alzheimer's (AD). Considered the brain's first line of defense, the Blood-Brain Barrier (BBB) and perivascular microglia work in tandem to protect the brain from circulating neurotoxic molecules like DEP. Importantly, there is a strong association between AD and BBB dysfunction, particularly in the Aß transporter and multidrug resistant pump, P-glycoprotein (P-gp). However, the response of this efflux transporter is not well understood in the context of environmental exposures, such as to DEP. Moreover, microglia are seldom included in in vitro BBB models, despite their significance in neurovascular health and disease. Therefore, the goal of this study was to evaluate the effect of acute (24 hr.) DEP exposure (2000 µg/ml) on P-gp expression and function, paracellular permeability, and inflammation profiles of the human in vitro BBB model (hCMEC/D3) with and without microglia (hMC3). Our results suggested that DEP exposure can decrease both the expression and function of P-gp in the BBB, and corroborated that DEP exposure impairs BBB integrity (i.e. increased permeability), a response that was significantly worsened by the influence of microglia in co-culture. Interestingly, DEP exposure seemed to produce atypical inflammation profiles and an unexpected general downregulation in inflammatory markers in both the monoculture and co-culture, which differentially expressed IL-1ß and GM-CSF. Interestingly, the microglia in co-culture did not appear to influence the response of the BBB, save in the permeability assay, where it worsened the BBB's response. Overall, our study is important because it is the first (to our knowledge) to investigate the effect of acute DEP exposure on P-gp in the in vitro human BBB, while also investigating the influence of microglia on the BBB's responses to this environmental chemical.

Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases.

Amelanotic melanoma can have a varied appearance both clinically and microscopically. Here, we present our experiences with 75 cases of amelanotic melanoma defined clinically as a non-pigmented lesion and histopathologically as a tumor lacking significant melanization. We evaluated microscopic features such as morphology, mitotic count, nuclear atypia and presence of solar elastosis. Our amelanotic melanomas exhibited the following morphology: epitheloid (72%), spindled (18.7%) or desmoplastic (5.3%). In addition, we obtained patient information and clinical presentations on most of the cases (74/75; 98.7%) and follow-up data on 40% (30/75) of the cases. The majority of amelanotic melanomas in men were found on the trunk (13/45; 29%), head and neck (12/45; 26.7%), and lower limb (13/45; 29%) and in women were found on the lower limb (12/30; 40%), upper limb (10/30; 33.3%) and head and neck (6/30; 20%). In addition, we found that an increase in mitotic index correlated with worse survival (p < 0.026), whereas there were no differences in survival for other pathological features, such as nuclear atypia or solar elastosis. Furthermore, in cases with available tissue, all amelanotic melanoma expressed microphthalmia-associated transcription factor and tyrosinase, suggesting that the tumor cells retained melanocytic lineage and an enzyme in melanin formation, respectively. As the occurrence of amelanotic melanoma and the expression melanoma markers were similar to pigmented melanoma, we favor that amelanotic melanoma represents a subtype of melanoma rather than poorly differentiated or de-differentiated melanoma.

Minocycline-induced hyperpigmentation in multibacillary leprosy.

Minocycline has been used in the treatment of leprosy since the demonstration of its efficacy in inhibiting Mycobacterium leprae growth in 1987. Hyperpigmentation, a well-documented adverse effect, classically shows 3 clinical and histological patterns: type I consists of blue-black pigmentation in areas of current or previous inflammation, type II consists of blue-gray pigmentation of normal skin, often seen on the legs, and type III consists of diffuse muddy-brown pigmentation accentuated on sun-exposed sites. Whereas type I hyperpigmentation stains positively for hemosiderin and type III hyperpigmentation stains positively for melanin, type II hyperpigmentation stains positively for both. We describe 2 patients with leprosy on minocycline therapy who developed multiple patches of blue-gray pigmentation within preexisting leprosy lesions. Biopsies from both patients demonstrated deposition of brownish-black pigment granules within the cytoplasm of foamy histiocytes that was highlighted by both Perls and Fontana-Masson stains. Given the clinical and histological findings in our patients, it is as yet unclear whether this coexistent type I clinical pattern and type II histopathologic pattern of pigmentation is unique to multibacillary leprosy. These findings provide support for the existence of additional subtypes of minocycline-induced hyperpigmentation that do not adhere to the classic 3-type model described.

Verrucous lymphangioma circumscriptum.

A 19-year-old woman with a seven-year history of pruritic, grouped, verrucous papules and plaques on the left arm presented for consultation. The lesion slightly flattened in appearance with topical glucocorticoid treatment. The histopathological features were consistent with lymphangioma circumscriptum. This entity is the most common subtype of lymphangioma and presents with grouped, clear vesicles that may appear pink to purple. However, a rare verrucous type can present a diagnostic challenge. Whereas the definitive treatment option is surgical excision, other treatments, which include sclerotherapy, radiotherapy, and laser therapy, have been reported to cause resolution or improvement. In the future, propranolol may hold promise as a medical therapy for lymphangioma.

Generalized essential telangiectasia.

Generalized essential telangiectasia, which is a rare condition that is characterized by the progressive development of telangiectases on the skin, is a clinical diagnosis of exclusion. We present a 65-year-old man with a ten-month history of an asymptomatic eruption of the trunk and proximal aspects of the arms and hands that was comprised of macules and patches of telangiectases. The clinical presentation, associated diseases, hypotheses regarding pathogenesis, differential diagnoses, and reports on treatment modalities are reviewed. The relatively new association of this entity with systemic signs that include hemorrhage as well as the occurrence of generalized essential telangiectasia in patients with a history of hepatitis is discussed.

Balloon cell melanoma: a systematic review.

Balloon cell melanoma (BCM) is a rare presentation of malignant melanoma characterized by large, foamy melanocytes lacking pigmentation. This is a comprehensive review of the clinical, dermoscopic, and histological features among BCM cases reported in the literature. A systematic review of all case reports and series published since 1970 was conducted via MEDLINE, Embase, and Web of Science, using "balloon cell melanoma" and synonymous search terms. Our systematic search identified 76 cases (49% male, 51% female) of BCM in the literature. The mean age at presentation was 57.81 years. Prior skin cancer, particularly melanoma (47%), accounted for 58% of pertinent medical history. Prominent clinical exam findings included raised (46%), ulcerated (73%) lesions larger than 1 cm (68%) in the lower extremities (35%). Median Breslow thickness of primary BCM cases was 2.5 mm. Hairpin vessels (75%) and structureless architecture (75%) were predominant on dermoscopy. Notable histopathology included large (47%), vacuolated (58%) cells with foamy cytoplasm (62%) and conspicuous nucleoli (27%). Positive S-100 immunohistochemistry (73%) was most frequently employed to diagnose BCM. We observed 47% primary and 53% metastatic BCM cases. Of metastatic BCMs, balloon cells in the primary lesion were unknown in 48%, devoid in 33%, and present in 20% of cases. All metastases displayed predominant balloon cell morphology. BCM may represent an advanced phase in the progression of malignant melanoma. Improved awareness of BCM characteristics among clinicians may reduce the risk of misdiagnoses.

Leukemia cutis in association With Grover's disease.

Grover's disease (GD), or transient acantholytic dermatosis, is a persistent recurrent dermatosis that usually occurs in men older than 50 years. Rare cases of GD and hematologic malignancy in the same cutaneous biopsy specimen have been reported. We report a case of GD in association with leukemia cutis. A 72-year-old man with a history of myelodysplastic syndrome presented with numerous pruritic papules on the torso, which were clinically diagnosed as GD. A skin biopsy revealed foci of suprabasal acantholysis and dyskeratosis consistent with GD and dense aggregates of mononuclear atypical cells in the superficial dermis consistent with leukemia cutis. Direct immunofluorescence was negative. This case illustrates the need to consider a diagnostic skin biopsy in any patient who presents with classic clinical findings of GD if there is any indication that the patient may be at higher risk for a hematologic malignancy.

Erythrocytosis and thromboembolic events in transgender individuals receiving gender-affirming testosterone.

Erythrocytosis is a well-recognized consequence of exogenous testosterone, however its prevalence and contributions to thrombosis remain unknown in the context of gender-affirming hormonal therapy. We undertook a retrospective study of transgender and non-binary (TGNB) adults receiving exogenous testosterone. In the retrospective sample, 923 transgender individuals receiving testosterone were identified with 519 having documented pre- and post-testosterone hemoglobin and hematocrit (Hgb/Hct). The mean peak Hgb/Hct was 15.7 g/dL, and 47.0%. Mean time-to-peak Hgb/Hct was 31.2 months; 7.8% developed a hemoglobin >17.5 g/dL, whereas 20% developed a hematocrit of >50%. Testosterone dose reduction occurred in 42% of patients with erythrocytosis and 4.8% underwent phlebotomy. Thromboembolic events occurred in 0.9%, of which 80% had developed erythrocytosis by either Hgb or Hct, including two cases each of superficial and calf vein thrombosis as well as one ischemic stroke. We then performed an analysis of 14,294,784 hospitalizations from the 2016-17 US National Inpatient Sample (NIS), which identified 4141 admissions involving transgender individuals. Of those, seven had erythrocytosis with one concurrent venous thromboembolic event. Hematocrit >50% occurs in up to 20% of transgender individuals receiving testosterone. Despite the high incidence of erythrocytosis, thromboembolic events and hospitalizations involving erythrocytosis were uncommon.

Intraepidermal and dermal Merkel cell carcinoma with squamous cell carcinoma in situ: a case report with review of literature.

Merkel cell carcinoma (MCC), a rare aggressive primary cutaneous neuroendocrine carcinoma, occurs on sun-damaged skin, especially in the elderly. Its unique co-expression of cytokeratin 20 (CK20) and neuroendocrine markers, including neuron-specific enolase (NSE), is diagnostic. Most MCCs are located in the dermis, rarely has an intraepidermal component been reported. We report a case of MCC with an intraepidermal component admixed with squamous cell carcinoma in situ (SCCIS). We were able to identify the differences in the immunohistochemical expression pattern between that of the intraepidermal and the dermal components. Most intraepidermal neoplastic cells of MCC in this case showed a less intense immunoreactivity to CK20 and NSE compared to that of dermal neoplastic cells. This case reports an unusual occurrence of combined SCC and MCC that shows both intraepidermal and dermal components.