A Case-Based Review of Cutaneous CD30-Positive Lymphoproliferative Disorders.

CD30-positive lymphoproliferative disorders are a group of diseases which represent the second most common (30 percent) subgroup of cutaneous T-cell lymphomas. They present a challenging diagnosis given their similar findings histologically and clinically in comparison to other cutaneous pathologies. Use of immunohistochemical staining to identify CD30 positivity facilitates a more rapid development of the appropriate management plan. Here we present two cases of CD30-positive lymphoproliferative disorders (lymphomatoid papulosis and anaplastic large cell lymphoma), analyze the spectrum of CD30-positive lymphoproliferative disorders, and review potential mimics of these pathologies to ensure the proper workup, diagnosis, and management of such diseases.

A Case of Subacute Cutaneous Lupus Erythematosus and Review of Cutaneous Lupus Clinical Variants.

Lupus erythematosus (LE) is a complex autoimmune disease that presents with a wide variety of clinical and immunopathological features, making it challenging to reach a correct and prompt diagnosis. Patients with LE most frequently present with cutaneous and rheumatologic manifestations. As cutaneous findings may be the first sign of disease, their timely recognition is important for proper workup and management of LE. Here we present a case of subacute cutaneous lupus erythematosus (SCLE) and review the cutaneous manifestations of lupus erythematosus and the histopathological correlates to raise awareness and promote faster times to diagnosis and treatment.

Axillary Granular Parakeratosis.

We describe a case of an 85-year-old Caucasian female who presented to the dermatology clinic with pruritic, scaly hyperpigmented papules and plaques with surrounding erythema in the left axilla. Based on the history and physical examination, there was concern for possible varicella zoster infection, and the patient was started on valacyclovir 1000 mg three times daily for seven days. A shave biopsy was taken from the left axilla to confirm a diagnosis. Microscopic examination revealed compact hyperparakeratosis with keratohyalin granules throughout the parakeratotic stratum corneum as well as admixed eosinophils within the stratum corneum. The epidermis was acanthotic with irregular hyperplasia of the rete ridges. These microscopic findings supported a diagnosis of axillary granular parakeratosis, a benign skin condition caused by a defect in epidermal differentiation. Granular parakeratosis is seemingly rare but is felt to be an underreported condition. It is important for clinicians to be aware of the disease in order to correctly identify the lesions and reassure patients of its benign nature and provide appropriate treatment recommendations.

A Case-Based Review of Systemic Mastocytosis and Its Cutaneous Manifestations.

Mastocytosis represents an uncommon spectrum of disorders where mast cells proliferate and accumulate in different organs and tissues throughout the body, most frequently affecting the skin. Here we present a case of systemic mastocytosis and review the manifestations of cutaneous and systemic mastocytosis to raise awareness and try to reduce the typical delay in diagnosis.

Hamartomas of skin and soft tissue.

Hamartomas are benign lesions composed of aberrant disorganized growth of mature tissues. Choristomas are similar, except that they are composed of tissues not normally found at the anatomic site in which the lesion is arising. A wide range of hamartomas and choristomas can arise in the skin and soft tissue. Some of these may cause diagnostic difficulty and potentially be mistaken for neoplasms. Some neoplasms may resemble hamaratomas. Here we review the current clinical and pathologic features of these lesions, both common and rare, and discuss how to distinguish them from other entities in the differential diagnosis.

Myxofibrosarcoma of unusual sites.

BACKGROUND: Myxofibrosarcoma classically presents as a painless mass in the proximal extremities. Cutaneous myxofibrosarcomas arising in the head and neck and distal extremities are extremely uncommon. We present a series of 6 cases of myxofibrosarcoma presenting in the head and neck and acral locations. METHODS: Archives were searched using the term "myxofibrosarcoma" over a 6-year period (2009-2015). The clinicopathologic features of myxofibrosarcoma were recorded. Cases in the head and neck or acral locations were retrieved. When available, the patient's medical records were reviewed. RESULTS: Ninety-five cases of myxofibrosarcoma were identified over a 6-year period. Six patients were identified with myxofibrosarcoma arising in the head (n = 4, M:F 3:1), hand (n = 1, F) and foot (n = 1, F). Each had typical features of myxofibrosarcoma. Two of the tumors on the head were high-grade and had multiple recurrences, while the remaining 2 were intermediate grade. Both acral tumors were intermediate grade and 1 recurred locally within a year of diagnosis. CONCLUSIONS: Myxofibrosarcoma may rarely involve the head and neck and acral locations, and presentation in these sites is a potential source of diagnostic difficulty. Recognition of the characteristic histologic features of myxofibrosarcoma in conjunction with judicial use of immunohistochemical stains should allow for accurate diagnosis.

Scleroderma-like skin changes induced by checkpoint inhibitor therapy.

Checkpoint inhibitors have emerged as beneficial therapies in many different types of malignancy. The most common toxicities of checkpoint inhibitors are immune-related adverse events (irAEs). As clinical experience with these agents increases, more irAEs have been described. We report a case of scleroderma-like skin changes induced by checkpoint inhibitor therapy. A 61-year-old man was treated with nivolumab for oligometastatic renal cell carcinoma. He initially tolerated the therapy well, but after 16 treatments he began experiencing skin thickening and edema of the abdominal wall, which progressed down the trunk and legs. A punch biopsy revealed epidermal attenuation overlying thickened dermal collagen with entrapment and displacement of the eccrine coils and loss of periadnexal adipose tissue. Focally increased plasma cells were present near the junction of the dermis and subcutaneous adipose tissue. Loss of CD34 staining was seen throughout the dermis. These findings were consistent with a diagnosis of scleroderma. After discontinuation of nivolumab and initiation of steroid therapy, the patient's symptoms significantly improved. This case is among the first reports of scleroderma-like changes induced by a checkpoint inhibitor.

Sebaceous Carcinoma in Situ Masquerading Clinically and Histologically as Paget Disease of the Breast.

Sebaceous carcinoma in situ is a poorly understood and ill-defined entity. In situ sebaceous carcinoma exhibits a similar location pattern to its invasive counterpart in that most commonly has a periorbital distribution. Review of the literature found only seven cases of extraocular sebaceous carcinoma in situ. We present a unique and challenging case of sebaceous carcinoma in situ masquerading both clinically and histologically as Paget's disease of the breast. A 61-year-old female presented to her dermatologist complaining of a 6 mm erythematous waxy papule on her medial right breast. The patient's past medical history was significant for Muir-Torre syndrome. Clinically, the differential diagnosis included Paget disease of the breast, squamous cell carcinoma, and sebaceous carcinoma. A shave biopsy revealed an atypical proliferation of large single cells limited to the epidermis infiltrating in a pagetoid pattern, as well as cohesive nests of round neoplastic cells with mild nuclear atypia, prominent nucleoli, and vacuolated cytoplasm. Histologically, the differential diagnosis included Paget's disease of the breast, squamous cell carcinoma in situ, melanoma in situ, and sebaceous carcinoma in situ. A battery of immunohistochemical stains was performed including CK7, EMA, CAM5.2, CK20, and MART-1. The lesional cells were positive for adipophilin, factor XIIIa, CK7, and EMA and were negative for CAM5.2, CK20, and MART-1 supporting a diagnosis of sebaceous carcinoma in situ. Multiple deeper sections were examined and invasion beyond the epidermis was not identified. This case adds to the paucity of information available regarding extraocular sebaceous carcinoma in situ and warns clinicians of this potential diagnostic pitfall especially in patients with Muir-Torre syndrome.

Primary Cutaneous Osteosarcoma.

Primary cutaneous osteosarcoma is an exceedingly rare malignant mesenchymal neoplasm of the skin which produces bone, osteoid, or chondroid material and does not involve the underlying bone. The most common site for extraskeletal osteosarcoma is in the deep soft tissues of the thigh, upper extremities, and retroperitoneum; however, it may occur anywhere in the body. Involvement of the skin is rare and when it does occur it is more commonly due to metastatic disease rather than a primary malignancy. Only 16 cases of primary cutaneous osteosarcoma have been described in the literature. We report an uncommon case of primary cutaneous osteosarcoma. Our patient is an 84-year-old male with an unremarkable medical history who presented to the dermatology clinic complaining of a 0.5 x 0.4 cm pink flesh to translucent-appearing, shiny, papule on the right superior jawline which was not connected to the underlying bone. Clinically the differential diagnosis included basal cell carcinoma, trichoepithelioma, and other cutaneous adnexal tumors. An excisional biopsy was performed which demonstrated an unremarkable epidermis with a hypercellular reticular dermis with occasional large spindled cells with amphophilic cytoplasm. The deep dermis was involved by mature osteoid formation and infiltration of highly mitotically active, atypical epithelioid and spindled cells with abundant nuclear pleomorphism, amphophilic cytoplasm, and poorly defined cell borders. Occasional multinucleate forms were seen. Immunohistochemistry was performed which showed strong positive staining with vimentin. Without connection to the underlying bone, osteosarcoma of periosteal, parosteal, or osseous origin was excluded. Based on these histomorphologic findings, a diagnosis of primary cutaneous osteosarcoma was made. Our case adds to the dearth of literature regarding primary cutaneous osteosarcoma and provides primary care physicians, dermatologists, and pathologists much needed insight into this rare condition.

Coexistent Alpha-1 Antitrypsin Deficiency and Hereditary Hemochromatosis.

Alpha-1 antitrypsin (AAT) deficiency and hereditary hemochromatosis are systemic diseases inherited in an autosomal recessive fashion. The primary manifestation of AAT is early-onset pulmonary disease, while hemochromatosis primarily affects function of the liver, heart, and pancreas through excess iron deposition. No clear association between the two diseases has been delineated. We present a case in which a 34-year old female patient presenting with elevated liver enzymes during a visit for an unrelated acute illness was found to be a homozygous variant for AAT deficiency and hereditary hemochromatosis. A description of her presentation and clinical work up is included, along with a discussion of the epidemiology and clinical characteristics of each disease.

A proposed classification for follicular involvement by melanoma.

BACKGROUND: Folliculotropism in melanoma is poorly characterized and standard categorization for follicular involvement by melanoma is unavailable. We propose a logical categorization system. METHODS: We conducted a search of our archives over a 24-year period for cases mentioning the terms follicle, follicular, folliculotropic, folliculocentric and melanoma. RESULTS: We identified 90 cases of melanoma with involvement of the hair follicle. Distinct patterns were identified. The invasive patterns were primary follicular, folliculotropic and invasive arising from melanoma in situ (MIS) with extensive follicular involvement. Follicular involvement by MIS was either lentiginous, nested or a combination of both. A total of 29 invasive melanomas were identified. Of these 12 had invasive melanoma around the hair follicle, 2 were primary follicular melanomas, 7 showed folliculotropism and 3 were invasive melanomas arising from MIS around the follicle. Seventeen invasive melanomas had follicles only involved by MIS (9 nested, 6 nested and lentiginous and 2 lentiginous). A total of 61 cases of MIS with follicular involvement were identified; of these 33 were lentiginous, 10 nested and 18 both lentiginous and nested. CONCLUSION: We propose that the three distinct patterns of follicular involvement by invasive melanoma and the three distinct patterns of MIS will be valuable for logically categorizing involvement of the hair follicle by melanoma.

Disseminated Blastomycosis Mimicking Malignancy.

Blastomycosis is an endemic fungal infection commonly found within the Mississippi and Ohio River basins and Great Lakes region. While patients typically present with acute pneumonia, Blastomyces dermatitidis has the potential to spread hematogenously, resulting in disseminated infection of multiple organs. In this report, we describe a 57-year-old male with disseminated blastomycosis acquired in South Dakota. The diagnostic evaluation was confounded by concern for malignancy given the involvement of multiple locations, including brain, lungs, adrenal glands, and testes. Despite aggressive therapy with amphotericin B, the patient succumbed to this infection.

Sport concussion knowledge base, clinical practises and needs for continuing medical education: a survey of family physicians and cross-border comparison.

CONTEXT: Evolving concussion diagnosis/management tools and guidelines make Knowledge Transfer and Exchange (KTE) to practitioners challenging. OBJECTIVE: Identify sports concussion knowledge base and practise patterns in two family physician populations; explore current/preferred methods of KTE. DESIGN: A cross-sectional study. SETTING: Family physicians in Alberta, Canada (CAN) and North/South Dakota, USA. PARTICIPANTS: CAN physicians were recruited by mail: 2.5% response rate (80/3154); US physicians through a database: 20% response rate (109/545). INTERVENTION/INSTRUMENT: Online survey. MAIN AND SECONDARY OUTCOME MEASURES: Diagnosis/management strategies for concussions, and current/preferred KTE. RESULTS: Main reported aetiologies: sports/recreation (52.5% CAN); organised sports (76.5% US). Most physicians used clinical examination (93.8% CAN, 88.1% US); far fewer used the Sport Concussion Assessment Tool (SCAT1/SCAT2) and balance testing. More US physicians initially used concussion-grading scales (26.7% vs 8.8% CAN, p=0.002); computerised neurocognitive testing (19.8% vs 1.3% CAN; p<0.001) and Standardised Assessment of Concussion (SAC) (21.8% vs 7.5% CAN; p=0.008). Most prescribed physical rest (83.8% CAN, 75.5% US), while fewer recommended cognitive rest (47.5% CAN, 28.4% US; p=0.008). Return-to-play decisions were based primarily on clinical examination (89.1% US, 73.8% CAN; p=0.007); US physicians relied more on neurocognitive testing (29.7% vs 5.0% CAN; p<0.001) and recognised guidelines (63.4% vs 23.8% CAN; p<0.001). One-third of Canadian physicians received KTE from colleagues, websites and medical school training. Leading KTE preferences included Continuing Medical Education (CME) courses and online CME. CONCLUSIONS: Existing published recommendations regarding diagnosis/management of concussion are not always translated into practise, particularly the recommendation for cognitive rest; predicating enhanced, innovative CME initiatives.

Gone fishing: a unique histologic pattern in cutaneous angiosarcoma.

Cutaneous angiosarcoma is a rare but aggressive vascular malignancy that can present a diagnostic challenge due to a wide variety of clinical appearances and histologic features. Final diagnosis traditionally is yielded by corroborating the histologic and immunohistochemical findings with the clinical presentation; however, a histologic feature known as "fish in the creek," which consists of free-floating or tufted pleomorphic spindle cells within the vascular lumen, may be an additional diagnostic clue. In this study, we aimed to determine the diagnostic utility of this finding in cutaneous angiosarcoma. Our results suggest that "fish in the creek" has the potential to be an additional useful diagnostic tool for an otherwise challenging and deceptive malignancy.

Tracking postural stability of young concussion patients using dual-task interference.

OBJECTIVES: This study examined the diagnostic benefit of using dual-task interference balance testing in young concussion patients and the longitudinal changes in postural stability that occur relative to other standard clinical assessments of concussion injury. DESIGN: Longitudinal, case-control. METHODS: Eighteen patients (16.6 (1.6)y) diagnosed with a concussion provided 22 separate ratings to characterize the severity of their current concussion-related symptoms and were evaluated for postural stability at each of four clinical visits. Twenty-six injury-free adolescents (17 (2.8)y) performed balance testing on two occasions, separated by ∼1 week. RESULTS: There was a progressive decrease in self-reported symptoms from visit 1 to visit 4 (P<0.0001-0.001). A similar improvement occurred in postural stability, indicated by 95% ellipse area and velocity. However, the differences in ellipse area and velocity were significant only between visit 1 and the rest of the visits as a whole (P<0.0001-0.05). There was a significant difference between concussion patients and healthy, injury-free participants in ellipse area and velocity during visit 1. A group difference was also observed in ellipse area on visit 2, but only during the two balance tests that involved a concomitant secondary cognitive task. CONCLUSIONS: Improvements in postural stability coincide with reductions in reported symptoms, though apparent recovery of these selected measures of postural stability seemingly occurs sooner. Because of the distinguishing time course of recovery indicated by dual-task interference balance testing, this type of balance testing assessment may be particularly valuable in evaluating integrated functional impairment and recovery in young concussion patients.

Comparison and utility of King-Devick and ImPACT® composite scores in adolescent concussion patients.

UNLABELLED: The King-Devick (KD) oculomotor test has recently been advocated for sideline diagnosis of concussion. Although visual processing and performance are often impaired in concussion patients, the utility of KD as a concussion diagnostic tool is not validated. PURPOSE: To examine the diagnostic value of KD, by comparing KD with post-concussion symptom scale (PCSS) and ImPACT® composite scores. We hypothesized that KD would be correlated with visual motor speed/memory (VMS, VIS) and reaction time (RT), because all require cognitive visual processing. We also expected parallel changes in KD and PCSS across recovery. METHODS: Thirty-five concussed individuals (12-19 y; 18 females, 17 males) were evaluated with PCSS, ImPACT® composite and KD scores over four clinical visits (V). RESULTS: KD times improved with each visit (ΔV1-V2: 7.86±11.82; ΔV2-V3: 9.17 ± 11.07; ΔV3-V4: 5.30 ± 7.87 s) and paralleled improvements in PCSS (ΔV1-V2: 8.97 ± 20.27; ΔV2-V3: 8.69 ± 14.70; ΔV3-V4: 6.31 ± 7.71), RT (ΔV1-V2: 0.05 ± 0.21; ΔV2-V3: 0.09 ± 0.19; ΔV3-V4 0.03 ± 0.07) and VMS (ΔV1-V2: -5.27 ± 6.98; ΔV2-V3: -2.61 ± 6.48; ΔV3-V4: -2.35 ± 5.22). Longer KD times were associated with slower RT (r = 0.67; P<0.0001) and lower VMS (r = -0.70; P<0.0001), respectively. CONCLUSION: Cognitive visual performance testing using KD has utility in concussion evaluation. Validation would further establish KD as an effective ancillary tool in longitudinal concussion management and research.