Lesional Skin Biopsies Research Articles

Overview of Cutaneous Mycobacterial Infections.

Mycobacterial infections may affect any human organ and produce disseminated disease in immunocompromised individuals. Their most common clinical presentations include pulmonary, cutaneous (skin and soft tissues), and disseminated forms. The skin and soft tissues are frequent targets of affection by mycobacterial pathogens manifesting as localized or diffuse disease. Overall, infections due to Mycobacterium leprae, Mycobacterium ulcerans, and Mycobacterium tuberculosis are the most frequently recognized mycobacterial pathogens involving the skin and soft tissues. Additionally, all mycobacterial species of the nontuberculous group may also produce cutaneous disease. Of these, the most commonly identified organisms causing localized infections of the skin and subcutaneous tissues are the rapidly growing species (Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus complex), Mycobacterium marinum, and M. ulcerans. Since the skin and soft tissues are important protective barriers for environmental pathogens, their disruption often represents the portal of entry of nontuberculous environmental mycobacteria (soil, natural water systems, engineered water networks, etc.). Additionally, some mycobacterial diseases affecting cutaneous structures occur after exposure to infected animals or their products (i.e., Mycobacterium bovis). Mycobacterial infections of the skin and soft tissues may manifest with a broad range of clinical phenotypes such as cellulitis, single or multiple abscesses, subacute or chronic nodular lesions, macules, superficial lymphadenitis, plaques, nonhealing ulcers, necrotic plaques, verrucous lesions, and many other dermatologic manifestations. Geography and environmental exposure play an important role in the epidemiology of cutaneous mycobacterial infections. Mycobacterial infection of the skin and subcutaneous tissue is an important cause of human suffering in terms of morbidity, deformity, dysfunction, and stigma. The diagnosis of cutaneous mycobacterial infections is challenging requiring a low threshold of clinical suspicion for obtaining skin biopsies of cutaneous lesions for acid-fast staining and cultures, and molecular probe assays to detect the presence of mycobacterial pathogens. The choice of antibacterial therapy combinations and length of therapy for cutaneous mycobacterial infections is species-specific.

Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is a rare autoimmune skin disease caused by anti-Dsg1 pathogenic autoantibodies. It is considered as a Th2-mediated disease. Likewise, Th17 cells were recently described in the pathogenesis of the disease but their role is still unclear. We aimed to unravel the eventual implication of the IL23/Th17 pathway in the development of PF. A case-control study was conducted on 115 PF patients and 201 healthy controls using PCR-RFLP and AS-PCR methods. SNPs in IL23R, RORγt, IL17A, IL17F, IL17AR, TNFa, and STAT3 genes were genotyped. mRNA expression of IL23R and RORγt was evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations between IL23R>rs11209026, IL17A>rs3748067, IL17F>rs763780, and TNFa>rs1800629 and the susceptibility to PF were reported. Moreover, we revealed a significant increased frequency of circulating CD4+IL17+ cells as well as higher mRNA levels of RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt and IL23R mRNA expression was observed in lesional skin biopsies. In spite of the little size of specimens, our results provide converging arguments for the contribution of the IL23/Th17 pathway in the pathogenesis of PF.

Pulsed-dye laser as an adjuvant treatment for discoid lupus erythematosus: a randomized, controlled trial

Purpose: To evaluate the efficacy and safety of pulsed-dye laser (PDL) for discoid lupus erythematosus (DLE) in a double blinded, randomized, controlled fashion.Method: Forty-eight DLE lesions from nine patients were recruited. The lesions on one side of the body were randomized into the treatment group and the other side served as a control. Treatments with the PDL (595 nm) were delivered every four weeks for four consecutive months. The patients were evaluated at weeks 0, 4, 8, 12, 16 and 24. Erythema index (EI) and Texture index (TI) were obtained by Antera3D®. Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) and physician global assessment (PGA) scores were assessed in every visit. Lesional skin biopsies before and after the PDL treatment were taken from four patients.Results: The lesions treated with the PDL demonstrated significantly more decreases in EI, TI and improvement in PGA scores compared to the control. Though there was improvement of mCLASI in the laser group, the significance difference was not observed. Interestingly, real-time polymerase chain reaction showed a reduction in CXCL-9, 10, IFN-γ, IL-1β, TNF-α and TGF-β. Additionally, post-treatment DLE lesions demonstrated decreased CD3, CD4, CD8 and CXCR3-positive cells.Conclusions: Improvements of DLE can be achieved with PDL.

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene (TCRB) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory.

Performance of a computer-aided digital dermoscopic image analyzer for melanoma detection in 1,076 pigmented skin lesion biopsies

Digital dermoscopic image analysis of pigmented skin lesions (PSLs) has become increasingly popular, despite its unclear clinical utility. Unbiased, high-powered studies investigating the efficacy of commercially available systems are limited. To investigate the diagnostic performance of the FotoFinder Mole-Analyzer in assessing PSLs for cutaneous melanoma. In this 15-year retrospective study, the histopathologies of 1076 biopsied PSLs among a total of 2500 imaged PSLs were collected. The biopsied PSLs were categorized as benign or malignant (cutaneous melanoma) based on histopathology. Analyzer scores (0-1.00) for these PSLs were obtained and grouped according to histopathology. At an optimized cutoff score of 0.50, a sensitivity of 56% and a specificity of 74% were achieved. The area under the receiver operating characteristics curve was 0.698, indicating poor accuracy as a diagnostic tool. This study had a retrospective design and involved only a single institution. Our study reveals a low sensitivity of the scoring function of this digital dermoscopic image analyzer for detecting cutaneous melanomas. Physicians must apply keen clinical judgment when using such devices in the screening of suspicious PSLs.

Toll-like receptors 2, 4, and 9 expressions over the entire clinical and immunopathological spectrum of American cutaneous leishmaniasis due to Leishmania (V.) braziliensis and Leishmania (L.) amazonensis

Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L. (L.) amazonensis drives the infection in the opposite direction to ADCL (the lowest T-cell hypersensitivity pole). This study evaluated by immunohistochemistry the expression of Toll-like receptors (TLRs) 2, 4, and 9 and their relationships with CD4 and CD8 T-cells, and TNF-α, IL-10, and TGF-β cytokines in that disease spectrum. Biopsies of skin and mucosal lesions from 43 patients were examined: 6 cases of ADCL, 5 of BDCL, and 11 of LCL caused byL. (L.) amazonensis; as well as 10 cases of LCL, 4 of BDCL, and 6 of ML caused byL. (V.) braziliensis. CD4+ T-cells demonstrated their highest expression in ML and, in contrast, their lowest in ADCL. CD8+ T-cells also showed their lowest expression in ADCL as compared to the other forms of the disease. TNF-α+showed increased expression from ADCL to ML, while IL-10+and TGF-β+ showed increased expression in the opposite direction, from ML to ADCL. With regards to TLR2, 4, and 9 expressions, strong interactions of TLR2 and 4 with clinical forms associated with L. (V.) braziliensis were observed, while TLR9, in contrast, showed a strong interaction with clinical forms linked to L. (L.) amazonensis. These findings strongly suggest the ability of L. (V.) braziliensis and L. (L.) amazonensis to interact with those TLRs to promote a dichotomous T-cell immune response in ACL.

Protocolo diagnóstico de las infecciones por estreptococos de los grupos C y G

IntroductionGroup C and G β-hemolytic streptococci such as Streptococcus dysgalactiae subsp. equisimilis, and Streptococcus anginosus are opportunistic microorganisms that produce a wide range of infections in animals. Infections produced by these species in humans have a clinical spectrum similar to those produce by Group A streptococci and affect especially patients in the extreme ages of life, immunosuppressed with neoplasias, diabetes, alcoholism or injecting drug users. DiagnosisRapid detection of streptococcal antigen does not rule out infection by groups C and G as this technique only detects Group A antigens. It is necessary to carry out a bacteriological culture of the sample of interest according to the clinical presentation, such as pharyngeal swab, swab or skin lesion biopsy, abscess aspirate, blood, joint fluid, etc. TreatmentPenicillin remains the first choice for the treatment of infections produced by Groups C and G, taking into account the absence of resistance reported in the literature and its low cost. Third-generation cephalosporins and clindamycin are useful for the treatment of invasive infections. The high rates of resistance to macrolides in our environment discourage its use.

Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus erythematosus lesions and correlate with disease severity.

Lupus erythematosus is a chronic autoimmune disease characterized by remissions and exacerbations. Accumulated evidence indicated that matrix metalloproteinases (MMPs) are upregulated in inflammatory cells of cutaneous lupus erythematosus (CLE); however, the activity levels of these proteases have remained uncharacterized. To elucidate the significance of MMP-2, MMP-9, and TIMP-1 in CLE pathogenesis, gelatin zymography was used to investigate pro and active levels of MMP-2 and MMP-9 in lesional and perilesional skin biopsies obtained from twenty-two CLE patients. TIMP-1 protein levels were detected by ELISA in the biopsy specimens. The correlation between biochemical parameters and clinical characteristics of the disease was also evaluated. Significantly higher levels of active MMP-2, active MMP-9, proMMP-9, active/proMMP-2, and TIMP-1 were detected in lesional skin samples. Besides, the active/proMMP-9 was elevated in female and smoking patients. Active MMP-9 levels and active/proMMP-9 were also increased in elderly patients. Active MMP-9 levels were lower in patients who had smaller total damage score. Consistently, active/proMMP-9 and active/proMMP-2 were positively correlated with CLASI. Interestingly, in hydroxychloroquine or topical corticosteroid-treated patients, MMP-2/-9 activity levels were found to be higher compared to untreated patients. These findings suggest that increased MMP-2 and MMP-9 activities may contribute to the pathogenesis of CLE and cutaneous disease severity.

Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2–high atopic dermatitis disease endotype

Expression profiling of skin biopsy specimens has established molecular features of the skin in patients with atopic dermatitis (AD). The invasiveness of biopsies has prevented their use in defining individual-level AD pathobiological mechanisms (endotypes) in large research studies. We sought to determine whether minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes. We sampled nonlesional and lesional skin tape strips and biopsy specimens from white adult patients with AD (18 male and 12 female patients; age [mean±SE], 36.3±2.2years) and healthy control subjects (9 male and 16 female subjects; age [mean±SE], 34.8±2.2years). AmpliSeq whole-transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsy specimens, and clinical trait correlations were performed. Skin tape expression profiles were distinct from skin biopsy profiles and better sampled epidermal differentiation complex genes. Skin tape expression of 29 immune and epidermis-related genes (false discovery rate<5%) separated patients with AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of patients with AD exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes, including overexpression of IL13, IL4R, CCL22, CCR4 (log2 fold change=5.5, 2.0, 4.0, and 4.1, respectively) and at a pathway level by TH2/dendritic cell activation. Both expression and immunostaining of skin biopsy specimens indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing FcεRI. The type 2-high endotype group exhibited more severe disease by using both the Eczema Area and Severity Index score and body surface area covered by lesions. Minimally invasive expression profiling of nonlesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.

Comparison of matrix metalloproteinase-1 expression in tumor-associated and nontumor-associated skin in patients with basal cell carcinoma

Basal cell carcinomas (BCC) produce large varieties of matrix metalloproteinases (MMPs). MMP induction occurs as a consequence of acute ultraviolet exposure, and may be some of the enhanced enzyme expression in tumor-associated skin reflects a response to solar radiation rather than an effect of the tumor itself. Of the MMP family, MMP-1 (collagenase-1) is the most abundantly expressed in various skin conditions. The aim were to compare MMP-1 expression using immunohistochemistry in BCC different areas (tumoral, peritumoral, and safety margin) with nontumor associated, sun-exposed skin and to determine the exact role of MMP-1 in the pathogenesis of BCC and its invasiveness. This study included 24 BCC patients, who also represented the controls by taking punch biopsies from normal skin on the dorsa of their hands (as sun-exposed areas). Immunohistochemical assessment of MMP-1 in lesional skin biopsy and control biopsies was carried out. MMP-1 expression in peritumoral area of BCC was significantly higher than the tumoral area, safety margin, and control (P 60 years) showed greater MMP-1 expression compared to their counterparts in younger age group (P<0.05). Patients with outdoor occupations demonstrated greater expression of MMP-1 in control areas compared with control skin from patients not excessively sun exposed (P<0.05). A significantly greater MMP-1 expression was found in peritumoral areas of undifferentiated BCC (P<0.05) compared with differentiated BCC. MMP-1 may have a role in the propagation of BCC, mainly through the stromal cells (peritumoral area) surrounding the tumor nests. This effect is because of the presence of the tumor and not exclusively dependent on sunlight exposure.

Would Marjolin see it coming? Two unusual cases of squamous cell carcinoma

IntroductionCutaneous squamous cell carcinoma (SCC) is a common skin cancer, second in incidence only to basal cell carcinoma (BCC). The incidence of SCC increases significantly with age; thus, it is rarely diagnosed in young patients. In this paper, we present two cases of young patients who presented clinically with purulent lesions that were later diagnosed as large primary SCCs. Materials and methodsA review of the medical records of two patients who were admitted to the department of plastic surgery with a final clinical diagnosis of cutaneous SCC was conducted. Information of the review included history, physical examination, laboratory tests, imaging studies and histology. A literature review was also conducted and discussed. ResultsTwo female patients under the age of 45 presented with large, purulent lesions that were initially clinically suggestive of an infectious etiology. The lesions were surgically treated by incision and drainage without sending tissue samples to pathology. Biopsies of the lesions were performed to obtain a tissue diagnosis due to recurrence approximately one year after the initial treatment. Histological evaluation revealed well differentiated squamous cell carcinomas. Surgical intervention with wide excision with adjuvant chemotherapy was recommended based on biopsy and CT scan results. DiscussionAggressive behavior of SCC in young patients is uncommon. The patients in this report were diagnosed only one year after the first sign of the lesion. One patient was first diagnosed with an abscess, and the other with necrotizing fasciitis. The delayed diagnosis of SCC in these two patients is a potential contributing factor to the aggressiveness of the tumors. Therefore, it is imperative to perform skin biopsies of chronic or persistent purulent lesions to rule out malignancies including Marjolin’s ulcer. ConclusionAggressive SCC should be suspected in cases of persistent and relapsing purulent lesions in all patients.

Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.

Clinical and pathological features of myeloid leukemia cutis

BackgroundMyeloid leukemia cutis is the terminology used for cutaneous manifestations of myeloid leukemia. ObjectiveThe purpose of this study was to study the clinical, histopathological and immunohistochemical features of myeloid leukemia cutis. MethodsThis was a retrospective study of clinical and pathological features of 10 patients with myeloid leukemia cutis. ResultsOne patient developed skin lesions before the onset of leukemia, seven patients developed skin infiltration within 4-72 months after the onset of leukemia, and two patients developed skin lesions and systemic leukemia simultaneously. Of these patients, five presented with generalized papules or nodules, and five with localized masses. The biopsy of skin lesions showed a large number of tumor cells within the dermis and subcutaneous fat layer. Immunohistochemical analysis showed strong reactivity to myeloperoxidase (MPO), CD15, CD43 and CD45 (LCA) in most cases. NPM1 (nucleophosmin I) and FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication) mutations were identified in one case. Five patients with acute myelogenous leukemia and one patient with chronic myelomonocytic leukemia died within two months to one year after the onset of skin lesions. Study limitationsThis was a retrospective and small sample study. ConclusionsIn patients with myelogenous leukemia, skin infiltration usually occurs after, but occasionally before, the appearance of hemogram and myelogram abnormalities, and the presence of skin infiltration is often associated with a poor prognosis and short survival time. myeloid leukemia cutis often presents as generalized or localized nodules or masses with characteristic pathological and histochemical findings.

Bilateral endogenous endophthalmitis in disseminated histoplasmosis secondary to immunosuppression: A rare case report

We report the clinical course of a 47-year-old diabetic and hypertensive male who presented to us with diminution of vision in both eyes (OU) for 4 months. He was diagnosed with granulomatosis with polyangiitis and was treated with cyclophosphamide and steroids elsewhere. Before this, he was on steroids and methotrexate for probable sarcoidosis based on cavitary lesions in the lungs. During tapering of the steroids and so in relatively immunosuppressed status, he developed fever and maculopapulo-nodular skin lesions. Skin lesion biopsy confirmed Histoplasma capsulatum and he was started on systemic antifungals. Later, he developed bilateral endogenous endophthalmitis and was managed with intravitreal medications followed by vitrectomy with lensectomy OU. The patient regained vision and is maintaining the same until 1 year of follow-up. Thus, in spite of its rare occurrence, H. capsulatum should be considered as a cause of endogenous endophthalmitis in an immunosuppressed host with systemic histoplasmosis.

A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic) nevi

Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen. To evaluate the clinical and histopathologic outcomes of in toto biopsy of DN using a predetermined margin of normal skin. We conducted a prospective study of a saucerization method using a defined 2-mm margin in patients undergoing biopsy of a pigmented skin lesion. We performed 151 biopsies in 138 patients. Overall, 137 of 151 lesions subjected to biopsy (90.7%) were melanocytic: 86 DN (57.0%), 40 nevi without atypia (26.5%), and 11 melanomas (7.3%). Of 78 DN, 68 (87.2%) were removed with clear histopathologic margins (8 DN were excluded because of inadequate processing). There was no clinical evidence of recurrence at any of the biopsy sites that were simply observed (i.e., not re-excised) over a median of 16.9months. There were few biopsies performed on the face. The complete histopathologic removal of nearly 9 of 10 DNusing a peripheral margin of 2mm of normal skin and a depth at the dermis and subcutaneous fat junction has the potential to decrease second procedures at DN biopsy sites, thereby decreasing patient morbidity and saving health care dollars.

Zoster? I Think Not: A Rare Site of Metastatic Colon Cancer

Skin metastasis of solid tumors accounts for only 2% of all skin tumors, most commonly occurring in primary breast and lung cancer. Cutaneous metastatic disease of colorectal cancer (CRC) is a rare phenomenon only occurring in about 5% of cases. A 49 year old man with microsatellite unstable, KRAS mutated, BRAF wild-type stage IV colon adenocarcinoma complicated by a malignant pleural effusion and pulmonary embolism on apixaban presented with shortness of breath and pruritic rash for one month. He had nausea, vomiting, and abdominal pain. Physical exam showed tachycardia to 115bpm, bulky bilateral anterior cervical lymphadenopathy, and a non-tender abdomen. His skin exam revealed multiple erythematous grouped papules scattered over a dusky erythematous large patch involving the left trunk. Chest x-ray showed new left pleural effusion with improvement of prior right pleural effusion. Labs showed hyponatremia 130mmol/L, hemoglobin 12.9g/dL, and WBC 14.4K/UL. The patient underwent thoracentesis with catheter placement for management of recurrent pleural effusion. He was started on empiric valacyclovir for suspected zoster without improvement in lesions. Biopsy of skin lesions was performed showing cutaneous metastases of colon adenocarcinoma. Valacylovir was discontinued, and the patient was discharged home with oncology follow up to start treatment with pembrolizumab given the microsatellite instability status of his malignancy. The most common site of cutaneous metastasis in CRC is the abdomen, affecting prior incision sites. Cutaneous metastatic cancer can have a variety of appearances. Color may range from flesh-like to violaceous and lesions may be single or multiple, firm, painless, mobile, and nodular. Appearance may mimic lipomas or epidermal cysts. Less frequently lesions may mimic an infectious process with a presentation that appears as a more erythematous indurated lesion but may in fact be inflammatory metastatic carcinoma. Histologic and genetic features may resemble the primary tumor. Awareness of cutaneous metastatic disease is important as it generally indicates widespread disease and is considered a poor prognostic sign. Treatment options may include wide local excision for isolated lesions, however extensive cases may require palliative systemic therapy. As skin lesions may mimic other benign processes, biopsy should be performed on suspicious skin lesions in patients with known cancer as it could signify cutaneous disease spread.Figure: Left trunk skin with multiple grouped papules scattered over a large erythematous skin patch. Biopsy was consistent with colon adenocarcinoma.

The Inherited Pneumothorax

SESSION TITLE: Sarcoidosis and Cystic Lung Disease SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Birt-Hogg-Dubé (BHD) syndrome is a rare, autosomal dominant pulmonary-cutaneous disorder that affects roughly 200 families worldwide. It is characterized by cutaneous fibrofolliculomas, recurrent pneumothoraces, pulmonary cysts and a predisposition for bilateral renal cancer. Due to varying manifestations, this under-recognized disease warrants our consideration. Here, we present a case of BHD syndrome with recurrent pneumothoraces and distinct cutaneous manifestations. CASE PRESENTATION: A 59-year-old female with family history for lung cysts and renal cancer was referred to pulmonary clinic after multiple hospitalizations for acute dyspnea. Patient had recurrent spontaneous pneumothoraces over four months requiring thoracostomy tubes and surveillance. Physical examination was significant for tachypnea, decreased right-sided breath sounds, hyperresonance to percussion, and small dome-shaped papules on face. Chest X-ray revealed chronic interstitial changes with a large right-sided pneumothorax. CT chest post thoracostomy therapy showed residual small right hydropneumothorax with paraseptal emphysematous changes within both lungs. Skin biopsies of papular lesions confirmed fibrofolliculomas, which prompted genetic analysis unveiling FLCN gene mutation. Upon follow-up, patient was advised to undergo pleurodesis, avoid smoking, air travel and scuba diving, and has been under close surveillance for associated malignancies. DISCUSSION: The combination of recurrent spontaneous pneumothoraces and fibrofolliculomas distinguish BHD syndrome from other cystic lung diseases. The basilar predominance of cysts is different from those of other cystic lung diseases. Earlier intervention with pleurodesis may reduce recurrence of pneumothorax. (1) The differential includes Marfan syndrome, Ehlers-Danlos syndrome, Cutis laxa, Lymphangioleiomyomatosis, Brooke-Spigler syndrome and Langerhan cell histiocytosis. Fibrofolliculomas are skin lesions that consist of hair follicle epithelium and mesenchyme. They appear as 2-4 mm waxy, white, dome-shaped papules involving the head and neck for which skin biopsy is the standard for diagnosis. (2) The risk of renal cancer requires routine surveillance with magnetic resonance imaging. CONCLUSIONS: Birt-Hogg Dubé syndrome represents a rare inherited constellation of skin, lung and kidney manifestations distinguished by fibrofolliculomas. The diagnosis demands genetic counseling, chromosomal analysis, lifestyle modifications, management of pneumothoraces, and evaluation for various malignancies. This case highlights the importance of a thorough physical examination and multidisciplinary team approach. Reference #1: Gupta N, Seyama K, McCormack F. Pulmonary manifestations of Birt-Hogg-Dubé syndrome. Familial Cancer. 2013;12(3):387-396. doi:10.1007/s10689-013-9660-9. Reference #2: Butnor K, Guinee D. Pleuropulmonary Pathology of Birt-Hogg-Dubé Syndrome. The American Journal of Surgical Pathology. 2006;30(3):395-399. doi:10.1097/01.pas.0000183571.17011.06. DISCLOSURE: The following authors have nothing to disclose: Sachin Patel, Latrisha Wright, Simha Jagadeesh, Muhanad Hasan No Product/Research Disclosure Information

Chronic hand eczema: is IL-36α helpful in diagnosis and classification?

Chronic hand eczema (CHE) is not a homogenous disease, necessitating complex differential diagnostics. Interleukin (IL) -1 family members are significantly up-regulated in ACD and psoriasis patients skin. The present study aims to deepen the knowledge about clinical assessment and characterization of patients affected by chronic hand dermatitis (CHD) as well as to investigate the role of possible biomarkers which may help in the diagnostic process. An observational case-control study was performed enrolling 30 CHD patients and 20 healthy controls. Each patient underwent detailed medical history, clinical examination, epicutaneous patch test, and lesional skin biopsies for histological and immunohistochemical analysis. Patient history, clinical examination and patch testing led us to a final CHD characterization in only 8/30 subjects (26.7%). In the remaining subjects, clinical and histological features suggested a diagnosis of psoriasis in 9/22 (30%) and idiopathic chronic hand eczema (CHE) in 13/22 (43.3%). Trying to find a possible marker for the latter dermatosis, we analyzed IL-1 family in all the recruited subjects. IL-1 members were increased in all conditions, but IL-36α was the only analyzed cytokine able to characterize patients who end up with a diagnosis of idiopathic CHE. In conclusion, we can assess that medical history and patch testing remain essential investigations in CHD patients even if not always sufficient to perform a final diagnosis. Moreover, IL-1 members are probably involved in CHE skin inflammation, with IL-36α being a possible future biomarker which might help in the complex diagnostic process of CHE.

An Unusual Case of Drug-Induced Linear IgA Bullous Disease

An Unusual Case of Drug-Induced Linear IgA Bullous Disease

Uterine intravascular lymphoma as a cause of fever of unknown origin.

Primary intravascular large B cell lymphoma (IVL) remains a diagnostic challenge because of non-specific clinical, laboratory and imaging findings. The aim of the study was to analyse the major characteristics of IVL with uterine involvement. We retrospectively collected features of IVL with uterine involvement that was proven histologically or demonstrated by significant 18FDG uptake on 18FDG-PET/CT. Findings were compared to a comprehensive literature review. Five patients were identified. All of them were admitted for fever of unknown origin (FUO), with haemophagocytic lymphohistiocytosis in three cases. None had gynaecological symptom, contrasting with the literature data. Structural imaging (including whole-body CT scan and pelvic RMI) failed to yield any diagnosis. 18FDG-PET/CT showed intense uterine uptake in all cases. Endometrial biopsy was performed in three cases and was positive in one. Diagnosis was obtained from coelioscopic iliac adenopathy biopsy in one case and from total hysterectomy in another. Punch biopsy of skin lesions led to diagnosis in the two remaining cases. Bone marrow biopsy was normal in all cases. Clinicians should be aware of potential isolated uterine involvement in IVL, especially in elderly women with FUO. Normal structural imaging does not rule out the diagnosis and 18FDG-TEP/CT should be performed to guide high-yielding biopsy.