A case report of granulomatous lymphomatoid papulosis.

Lymphomatoid papulosis is a chronic CD30-positive cutaneous lymphoproliferative disorder that is characterized by recurring red-brown necrotic papules. It exhibits a wide spectrum of histopathologic findings and is often associated with cutaneous T-cell lymphomas. Six different histological subtypes have been classified by the WHO, but there is limited understanding regarding rare histopathologic variants. We describe a 51-year-old man who presented with recurring, necrotic papules for 6 years that progressed to involve the face, scalp, trunk, axilla, and scrotum. Histopathology demonstrated sarcoidal granulomas, along with a CD30-positive T cell infiltrate which demonstrated clonality by T cell receptor gamma gene rearrangement. A diagnosis of lymphomatoid papulosis associated with granulomas was established based on the clinical and histopathologic presentation. The clinical understanding of granulomatous lymphomatoid papulosis is limited in the available literature and more awareness of this histopathologic variant is required for accurate classification of this disorder.

Cutaneous solitary fibrous tumor: Report of three cases with review of histopathological mimics.

Solitary fibrous tumor (SFT) is a relatively uncommon spindle cell mesenchymal neoplasm that is most often based on the pleura but may rarely arise in extrapleural locations, including the skin. Herein, we describe three cases of cutaneous SFTs. SFT is characterized by epithelioid and spindle cells arranged in random patterns with focal prominent stromal collagen and pericytomatous vessels. Immunohistochemical evaluation is required for definitive distinction of SFT from other benign and malignant cutaneous spindle cell neoplasms. Although aggressive biologic behavior is uncommon, accurate diagnosis of it is required for prognostication and counseling. CD34, bcl-2, and CD99 stains are positive in SFT, but not specific. STAT6 is the most sensitive and specific immunohistochemical marker to confirm diagnosis of SFT.

Sclerosing perineurioma: a rare benign tumor in a pediatric patient.

A 15-year-old boy presented to outpatient dermatology clinic for evaluation of a lesion on the hand. Originally small and asymptomatic, the lesion had rapidly enlarged in the six months prior to evaluation. A shave biopsy was performed and histopathologic evaluation demonstrated a well-circumscribed nodular proliferation of dense, bland, epithelioid to spindle cells on a fibrillary background. Tumor cells were diffusely epithelial membrane antigen (EMA) positive; S100 and Melan-A were negative. These findings are consistent with a diagnosis of sclerosing perineurioma. This case illustrates the presentation of sclerosing perineurioma in a pediatric patient and we review the pertinent pathologic and immunohistochemical findings necessary for diagnosis. It is imperative to distinguish this entity from other soft tissue tumors on the hand, both benign and malignant, to avoid overly aggressive surgical intervention.

Knuckle pads: an ancient disease frequently misdiagnosed because of minimal modern attention.

Knuckle pads are benign painless papules and nodules that most commonly appear on the extensor surfaces of the proximal interphalangeal joints. Knuckle pads are frequently misdiagnosed due to their location overlying joints, which can lead to costly interventions and patient discomfort for a relatively harmless condition. We describe a 44-year-old woman who presented with mildly painful nodules on multiple bilateral proximal interphalangeal joints. The patient did not have a family history of fibromatosis and the rheumatoid factor was negative. Histology showed mild epidermal hyperkeratosis, papillomatosis, and acanthosis with a deep dermal, poorly circumscribed, proliferative nodule made of spindled myofibroblasts without cytological atypia. The diagnosis of knuckle pads was established based on the clinical and morphological presentation of the nodules. Treatment with intralesional triamcinolone acetonide injection produced significant clinical improvement. Our findings highlight the challenging diagnosis of knuckle pads and the importance of increasing the familiarity of knuckle pads in modern medical practice.

Reactive angioendotheliomatosis associated with antiphospholipid syndrome.

Reactive angioendotheliomatosis (RAE) is an uncommon, benign, antiproliferative condition associated with systemic diseases that may cause occlusion or inflammation of the vascular lumina. A link between antiphospholipid syndrome (APS) and RAE has been reported a few times in the literature. Herein, we present a unique case of RAE diagnosed in a patient with primary APS who was well-managed on warfarin and rituximab with no recent thrombotic events. As RAE can precede or follow a diagnosis of APS, the presence of the condition indicates a need to workup for APS and to ensure those with the condition are adequately anticoagulated. However, as demonstrated in this case, the condition can still occur in patients who are adequately anticoagulated.

Tick Bite-Associated Morphea: A Case Report.

Borrelia burgdorferi, the causative organism of Lyme disease, has been linked to the development of scleroatrophic skin conditions including morphea, although this association remains controversial. The possibility that tick bite with or without concurrent Borrelia infection instigates that morphea development is important to recognize because this could prompt further workup for Lyme disease, or other tick-borne illness, which, when untreated, can have devastating consequences. Here, we report a case of a woman with a history of previous tick bite in the location of morphea. This prompted further workup, including serologies that were negative for borrelia. The patient declined empiric treatment with doxycycline. It is important to be aware that morphea may represent a consequence of tick bite because this can alter patient management.

An amelanotic nail bed melanoma presenting as persistent onychodystrophy.

Nail apparatus melanomas are rare and may present with a wide variety of clinical presentations. In particular, the amelanotic subtype can pose a diagnostic challenge, often leading to a poor prognosis related to a delayed diagnosis. We report a 69-year-old man with an unusual subungual amelanotic melanoma presenting as a persistent single nail dystrophy that was repeatedly treated as onychomycosis. Owing to the delayed diagnosis of the melanoma and to minimize recurrence risk, the patient underwent a partial amputation of his left thumb.

Pseudoxanthoma elasticum-like changes in nonuremic calciphylaxis: Case series and brief review of a helpful diagnostic clue.

Calciphylaxis is a rare syndrome of vascular calcification with thrombosis that occurs most often in patients with end-stage renal disease, and it frequently portends a guarded prognosis. Rarely, nonuremic calciphylaxis (NUC) may occur; in this context, a strongly supportive histology is crucial in establishing the diagnosis. Herein, we describe 2 cases of NUC associated with pseudoxanthoma elasticum-like changes, identified in both initial nondiagnostic and subsequent diagnostic biopsy specimens. This unusual but helpful histologic finding may support the early diagnosis and treatment of a potentially life-threatening disease in the context of subtle histopathologic vascular changes or in the absence of classic clinical or laboratory findings.

Mycobacterial Spindle Cell Pseudotumor (MSP): A Case Report.

Mycobacterial spindle cell pseudotumor (MSP) is a rare proliferation of spindle-shaped histiocytes that occurs most frequently in lymph nodes but has also been documented in the skin, soft tissue, abdomen, and other sites. These lesions contain acid-fast mycobacteria, most commonly Mycobacterium avium complex. Fewer than 10 cases of cutaneous MSPs have been published, and most have occurred in immunocompromised patients, either due to human immunodeficiency virus (HIV) infection or immunosuppressive medications. The differential diagnosis includes Kaposi's sarcoma and other spindle cell neoplasms, which can be distinguished based on histology and special stains. We present the case of a 76-year-old man with HIV infection who presented with a diffuse rash on his arms and legs. A pretibial biopsy was performed and revealed tubercular MSP.

Serologic Abnormalities in Macular Lymphocytic Arteritis with Case Presentation.

Macular lymphocytic arteritis (MLA) is an indolent cutaneous small-medium-vessel vasculitis characterized by widespread asymptomatic livedo racemosa. A number of serologic abnormalities have been reported including an elevated erythrocyte sedimentation rate and antibodies associated with antiphospholipid antibody syndrome. We present a case of MLA with multiple serologic abnormalities, including those that have yet to be reported, such as anti-U1 ribonucleotide protein, anti-RNA polymerase III, anti-smith, and anti-proteinase 3 antibodies. We also provide a brief review of this unfamiliar entity with a focus on the appropriate workup.

Comparative genome hybridization analysis of laser-capture microdissected in situ melanoma.

BACKGROUND: The progression of melanoma occurs through discrete stages with known clinical and histologic features. Although many molecular events that occur during the progression of invasive and metastatic melanomas have been elucidated, there is limited knowledge of genetic changes that occur in the earliest stages of melanoma development. In this pilot study, we investigated genetic changes that happen in in situ melanoma so that we can better understand early melanoma development. MATERIALS AND METHODS: DNA was extracted from five laser-capture microdissected Clark's level III melanomas, five in situ melanomas and five compound nevi all from sun exposed skin. Array-based comparative genomic hybridization was performed using Agilent 44 K platform. RESULTS: The group of Clark's level III melanomas was characterized with multiple large deletions and duplications. In the group of in situ melanoma, deletions and duplications were limited in size. Deletions in in situ melanomas were present only on chromosomes 13q and 16q. Compound nevi did not show any significant chromosomal aberrations. CONCLUSION: In situ melanomas show characteristic chromosomal aberrations that are limited compared to melanomas that invade the dermis. Deletion of 13q found in in situ melanomas, which encompass the Rb1 tumor suppressor gene, might be one of the first events in the development of melanoma.

Subcutaneous intravascular pyogenic granuloma: a case report and review of the literature.

Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a common vascular proliferation that often occurs after minor injury or infection of the skin. Typically these lesions occur in the superficial dermis; although rare, subcutaneous and intravascular lesions can occur. We present a case of PG with the unusual features of being both a deep subcutaneous and intravascular lesion localized to the forehead without antecedent trauma. We also review the literature on PG and discuss the differential diagnosis.

Autologous Fat Transfer for Scar Prevention and Remodeling: A Randomized, Blinded, Placebo-controlled Trial.

Autologous fat transfer-also referred to as fat grafting-has been reported to provide beneficial effects to overlying scar and skin. Despite procedural frequency, there is a paucity of high-level evidence guiding the surgeon in technique, patient selection, and efficacy. METHODS: A multicenter, double-blinded, randomized, internally placebo-controlled trial was performed with an aim to qualitatively and quantitatively evaluate the impact of autologous fat transfer on the quality of overlying scar tissue. Fat-grafted scars were evaluated and compared with paired, saline-injected "control" scars. Subjective and objective metrics were evaluated in treated sites for 12 months after treatment. RESULTS: Blinded qualitative results demonstrated a statistically significant improvement in scar quality over time in fat-grafted scars. However, these improvements were not found to be statistically different from changes noted in scars treated with saline. In addition, objective metrics did not statistically differ between saline-injected and autologous fat-grafted scars. CONCLUSIONS: Our results demonstrate that autologous fat grafting can improve the qualitative profile of a scar from both the patient and observer perspectives. However, there was no difference in improvement when compared with scars that were treated with saline in a randomized and blinded fashion. These results demonstrate that any improvements in scar quality related to fat grafting are also achieved using saline and suggest that mechanisms other than cell activity may be at play. Additional randomized, blinded, placebo-controlled trials are required to either corroborate or contest the putative beneficial effect(s) of adipose tissue on scar remodeling.

Pyoderma gangrenosum masquerading as necrotizing fasciitis.

Necrotizing fasciitis is a fulminant advancing soft tissue infection characterized by widespread fascial necrosis, which can result in significant morbidity and even death. This condition requires prompt diagnosis and aggressive management with extensive surgical debridement and appropriate antibiotic coverage. Pyoderma gangrenosum, in contrast, is a noninfectious inflammatory condition of the skin that typically does not require surgical management. Both conditions can present with extensive ulceration and tissue necrosis, and close clinical-pathologic correlation is required to make the appropriate diagnosis. We present a case in which the diagnosis of pyoderma gangrenosum was initially elusive and serves to illuminate the diagnostic pitfalls in dealing with these entities.

Lichen planus-like keratosis: clinicopathological evaluation of 1366 cases.

BACKGROUND: Lichen planus-like keratosis (LPLK) is a frequent skin lesion usually biopsied to rule out basal cell carcinoma (BCC). Because of overlapping histopathological characteristics, LPLK is frequently muddled with lichen planus (LP), lichenoid actinic keratosis (LAK), and lupus erythematosus (LE). OBJECTIVE: To investigate the clinical and histopathological characteristics of LPLK. METHODS: A clinicopathologic review was performed of all LPLK cases (1366) signed in one calendar year in a busy academic practice. RESULTS: LPLK occurs mostly as a single lesion (97%) with the chest (41.4%) being the most common site. It is almost equally present in women and men (51.5%-48.5%). The most common clinical concern (65%) is basal cell carcinoma. Parakeratosis, red blood extravasation, and presence of dermal eosinophils and plasma cells, usually not seen in lichen planus, are helpful signs to suggest LPLK but are seen only in a minority of cases. CONCLUSION: Clinicopathologic correlation is necessary to diagnose lichen planus-like keratosis, as the most consistent feature is a clinical history of a lesion/neoplastic process rather than an inflammatory process. There are histopathologic features that can help distinguish lichen planus-like keratosis from lichen planus; however, these features are nonspecific and lacking in almost half of the cases.

A gene signature of nonhealing venous ulcers: potential diagnostic markers.

BACKGROUND: Venous leg ulcers are responsible for more than half of all lower extremity ulcerations. Significant interest has been focused on understanding the physiologic basis on which patients fail to heal with standard therapy. OBJECTIVE: This study uses complementary DNA microarray analysis of tissue samples from healing and nonhealing venous leg ulcers to identify the genetic expression profiles from these dichotomous populations. METHODS: Ulcer size and chronicity, factors that have been identified as prognostic indicators for healing, were used to distribute venous leg ulcers as healing versus nonhealing. Punch biopsy samples were obtained from the wound edge and wound bed of all venous leg ulcers. The top 15 genes with differential expression greater than 2-fold between the two populations of wounds (P < .05) were reported. RESULTS: Significant differences were demonstrated in the expression of a diverse collection of genes, with particular differences demonstrated by genes coding for structural epidermal proteins, genes associated with hyperproliferation and tissue injury, and transcription factors. LIMITATIONS: Small sample size may mitigate potential clinical implications of findings. CONCLUSIONS: The genetic expression profiles displayed here may have implications for the development of novel therapies for chronic venous leg ulcers, and may also serve as prognostic indicators for wound healing.

Preservation of biomolecules in breast cancer tissue by a formalin-free histology system.

BACKGROUND: The potential problems associated with the use of formalin in histology, such as health hazards, degradation of RNA and cross-linking of proteins are well recognized. We describe the utilization of a formalin-free fixation and processing system for tissue detection of two important biopredictors in breast cancer - estrogen receptor and HER2 - at the RNA and protein levels. METHODS: Parallel sections of 62 cases of breast cancer were fixed in an alcohol-based molecular fixative and in formalin. Molecular fixative samples were processed by a novel formalin-free microwave-assisted processing system that preserves DNA, RNA and proteins. Formalin-fixed samples were processed using the conventional method. Estrogen receptor was assessed by immunohistochemistry and real-time PCR. HER2 was assessed by immunohistochemistry, FISH, CISH and real-time PCR. RESULTS: The immunohistochemical reaction for estrogen receptor was similar in molecular- and formalin-fixed samples (Spearman Rank R = 0.83, p < 0.05). Also HER2 result was similar to that of formalin-fixed counterparts after elimination of antigen retrieval step (Spearman Rank R = 0.84, p < 0.05). The result of HER2 amplification by FISH and CISH was identical in the molecular fixative and formalin-fixed samples; although a shorter digestion step was required when using the former fixative. Real-time PCR for both estrogen receptor and HER2 were successful in all of the molecular fixative specimens. CONCLUSION: The formalin-free tissue fixation and processing system is a practical platform for evaluation of biomolecular markers in breast cancer and it allows reliable DNA and RNA and protein studies.