Erythematous Plaque Studded With Papules and Pustules in an Immunocompetent Patient.

A male patient was evaluated by the dermatology inpatient consult service after a 5-week history of a skin lesion on the right anterior thigh with intermittent itching and mild tenderness to palpation. What is your diagnosis?

Treatments on the horizon for locally advanced basal cell carcinoma.

Basal cell carcinoma (BCC) is one of the most common human cancers. Most cases of BCC are amenable to surgical and topical treatments with excellent prognosis if diagnosed timely and managed appropriately. However, in a small percentage of cases, it could be locally advanced BBC (laBCC) and not amenable to surgery or radiation, including recurrent, large tumors or tumors that invade deeper tissue. Hedgehog inhibitors (vismodegib and sonidegib) are approved as the first-line treatment of laBCC. PD-1 inhibitor immunotherapy (cemiplimab) is indicated for cases that progressed on or could not tolerate hedgehog inhibitors or when hedgehog inhibitors are contraindicated. Given the modest response and bothersome side effects of some of the agents above, there are reports of novel treatments, and clinical trials are currently evaluating multiple agents.

A Rare Presentation of Extragenital Bowenoid Papulosis.

Bowenoid papulosis is an uncommon skin disorder usually seen in the genital area and associated with human papillomavirus (HPV) infection. Clinically, patients usually present with solitary or multiple skin- to brown-colored papules. Plaque morphology of lesions and extragenital location are unusual. Diagnosis is mainly based on clinical presentation and confirmed with a skin biopsy demonstrating keratinocyte atypia. Chromogen in situ hybridization for HPV can also be done. Herein, we present a rare case of bowenoid papulosis with a plaque morphology on the face with no concomitant involvement of the anogenital, oropharyngeal, or periungual areas in an immunocompromised patient. Histopathologic sections stained positive with the in situ hybridization technique for high-risk oncogenic HPV serotypes (16, 18, 31, 33, 35, 45, 51, 52, and 56), confirming the diagnosis.

Concomitant hypertrophic lichen planus and squamous cell carcinoma: Clinical features and treatment outcomes.

BACKGROUND: Patients with hypertrophic lichen planus (HLP) and squamous cell carcinoma (SCC) diagnoses present clinicians with diagnostic and disease management challenges. OBJECTIVE: To better define the clinical and treatment outcomes of patients with concomitant diagnoses of HLP and SCC. METHODS AND MATERIALS: A retrospective review was performed from January 1, 2008, to July 31, 2015, at Mayo Clinic. Patients with a histologic diagnosis of HLP and SCC were included. Patient demographics, associated comorbidities, histopathologic characteristics, treatment, and outcomes were evaluated. RESULTS: Thirty-three patients were identified; 79% were female, and mostly the lower extremities were involved. Most of the SCCs were well-differentiated and in situ with the majority treated with destruction or excision. There were no cases of local recurrence, metastasis, or disease-specific death during the follow-up period (mean 55.8 months). CONCLUSION: Patients with diagnoses of both HLP and SCC appear to be a distinct population that is predominantly female with lesion predilection for the lower extremities. However, regardless of treatment modality or tumor size, there were no adverse outcomes. An initial trial of more conservative treatment measures with close follow-up may be reasonable with biopsy of lesions unresponsive to conventional treatment.

Evaluation of Auramine O staining and conventional PCR for leprosy diagnosis: A comparative cross-sectional study from Ethiopia.

BACKGROUND: Diagnosis of leprosy mainly relies on clinical examination due to the inconsistent sensitivity and poor reproducibility of the current laboratory tests. Utilisation of alternative methods to the standard Ziehl Neelsen (ZN), Fite-Faraco (FF) and Haematoxylin and Eosin (H&E) staining procedures may eventually improve leprosy diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this comparative study, the performance of the fluorescent Auramine O (AO) staining and polymerase chain reaction (PCR) was assessed with different skin samples using a combination of ZN, FF and H&E staining as the gold standard. AO, ZN, FF, H&E and PCR tests were performed on slit skin smears (SSS) and/or punch biopsies collected from 141 clinically confirmed leprosy cases and 28 non-leprosy skin samples. DNA was extracted from punch biopsies using two different methods with or without mechanical lysis. Sensitivities were 87.6%, 59.3% and 77% for H&E, ZN and FF, respectively, whereas it reached 65.5% and 77.9% for AO in SSS and tissue sections and 91.1% for PCR in tissue samples. Morover, samples with low bacillary index, sensitivity of AO staining (61.8%) was similar to FF (60%, p>0.05) and lower than PCR (86.6%, p<0.05). Sensitivity of PCR also increased (96.8%, p<0.05) when mechanical lysis was used during DNA extraction compared to enzymatic treatment alone (84.6%). CONCLUSIONS/SIGNIFICANCE: Our results showed that for diagnostic purposes, analysis of skin section is more sensitive than SSS, especially for samples with low bacillary load. AO staining on SSS and tissue sections was not significantly better than other routine diagnostic tests but considerably more user friendly. The sensitivity of PCR was higher than current standard methods and increased when combined with more efficient DNA extraction using mechanical and chemical lysis. Therefore, we recommend AO staining for the diagnosis of leprosy in lower health facilities such as health centres and district hospitals and PCR diagnosis at referral level and research centres.

Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia.

BACKGROUND: Leprosy reactions are a significant cause of morbidity in leprosy population. Erythema nodosum leprosum (ENL) is an immunological complication affecting approximately 50% of patients with lepromatous leprosy (LL) and 10% of borderline lepromatous (BL) leprosy. ENL is associated with clinical features such as skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. ENL is treated mainly with corticosteroids and corticosteroids are often required for extended periods of time which may lead to serious adverse effects. High mortality rate and increased morbidity associated with corticosteroid treatment of ENL has been reported. For improved and evidence-based treatment of ENL, documenting the systems affected by ENL is important. We report here the clinical features of ENL in a cohort of patients with acute ENL who were recruited for a clinico-pathological study before and after prednisolone treatment. MATERIALS AND METHODS: A case-control study was performed at ALERT hospital, Ethiopia. Forty-six LL patients with ENL and 31 non-reactional LL matched controls were enrolled to the study and followed for 28 weeks. Clinical features were systematically documented at three visits (before, during and after predinsolone treatment of ENL cases) using a specifically designed form. Skin biopsy samples were obtained from each patient before and after treatment and used for histopathological investigations to supplement the clinical data. RESULTS: Pain was the most common symptom reported (98%) by patients with ENL. Eighty percent of them had reported skin pain and more than 70% had nerve and joint pain at enrolment. About 40% of the patients developed chronic ENL. Most individuals 95.7% had nodular skin lesions. Over half of patients with ENL had old nerve function impairment (NFI) while 13% had new NFI at enrolment. Facial and limb oedema were present in 60% patients. Regarding pathological findings before treatment, dermal neutrophilic infiltration was noted in 58.8% of patients with ENL compared to 14.3% in LL controls. Only 14.7% patients with ENL had evidence of vasculitis at enrolment. CONCLUSION: In our study, painful nodular skin lesions were present in all ENL patients. Only 58% patients had dermal polymorphonuclear cell infiltration showing that not all clinically confirmed ENL cases have neutrophilic infiltration in lesions. Very few patients had histological evidence of vasculitis. Many patients developed chronic ENL and these patients require inpatient corticosteroid treatment for extended periods which challenges the health service facility in resource poor settings, as well as the patient's quality of life.

Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. METHODS AND RESULTS: Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. CONCLUSIONS: This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale.

Orthokeratotic Bowen disease: a histopathologic, immunohistochemical and molecular study.

BACKGROUND: Some examples of Bowen disease lack the characteristic broad parakeratosis making their histopathologic diagnosis particularly difficult in small and incomplete biopsies. MATERIALS AND METHODS: The archives of our dermatopathology laboratory were searched for cases of Bowen disease with >75% orthokeratosis (orthokeratotic Bowen disease) and classic Bowen disease (>25% parakeratosis). Selected specimens were evaluated histopathologically, using immunohistochemical stains (CK10, CK7, Bcl-2, p16 and Ki-67) and by DNA amplification/sequencing for human papilloma virus (HPV) subtypes. RESULTS: Among 102 consecutive samples 14 cases of orthokeratotic Bowen disease were identified. In comparison with 24 examples of classic Bowen disease, the orthokeratotic examples occurred more frequently in female and younger patients (p = 0.04 and 0.008, respectively) but shared most of the histopathologic features of classic Bowen disease except a preserved granular layer and relative absence of the eyeliner sign (p < 0.0001 and p = 0.042, respectively). Immunohistochemical staining patterns were similar between the two groups. HPV types 11, 16 and 58 were identified from five cases of orthokeratotic Bowen disease. CONCLUSION: Orthokeratotic Bowen disease is a distinct variant of squamous cell carcinoma in situ associated with HPV infection in less than half of the cases studied.

S100A6 expression in cutaneous smooth muscle neoplasms.

The S100A6 protein is expressed in a variety of tissues and distinct staining patterns in S100A6 immunohistochemistry may be useful in the differential diagnosis of difficult lesions. We evaluated the staining pattern of the S100A6 antibody in 22 cases each of pilar leiomyoma (LM), angioleiomyoma (ALM), and cutaneous leiomyosarcoma (LMS). S100A6 labeled both the nucleus and cytoplasm of myocytes in positive cases. About 64% of LM and 86% ALM had positive staining to the S100A6 antibody but predominantly in a weak staining pattern. In contrast, 95% of the LMS exhibited moderate to strong staining with the S100A6 antibody. The difference in the frequency of positive cases was statistically significant in the LM vs LMS comparison (p = 0.025), but we found intensity of staining to be of greatest practical utility. Analysis between the groups taking in to consideration differences in intensity of staining using the nonparametric rank sum (Mann-Whitney U test) demonstrated that there was a statistically significant difference between LM and LMS and between ALM and LMS. Weak or absent S100A6 staining supports a diagnosis of LM, whereas strong positive staining supports a diagnosis of LMS.

Nevoid melanoma: A study of 43 cases with emphasis on growth pattern.

BACKGROUND: Nevoid melanoma may be confused both clinically and histologically with benign nevi. OBJECTIVE: The aim of this study was to characterize the histologic features of nevoid melanoma. METHODS: Forty-three cases of nevoid melanoma from our laboratory were evaluated. RESULTS: Our study cases included 33 men and 10 women with mean age of 62 years. The back was the most common site followed by the arm. A clinical diagnosis other than melanoma was made in about 40% of the cases. Two architectural patterns were identified: Plaque and polypoid. Sheetlike confluence of melanocytes expanding the papillary dermis was seen in 60% of the cases. Nests disposed in parallel arrays at the base of the tumor (parallel theque pattern) were present in roughly 81% of our series. Mitoses were evident in one-third of cases ranging from less than 1 to 4 per square millimeter. Genomic abnormalities characteristic of melanoma were detected in 7 of 8 tested cases. LIMITATION: This is a descriptive study. No follow-up information was available for 32 of the 43 patients. In the other 11, follow-up was limited to the re-excision specimens. CONCLUSION: Characteristic growth patterns including confluence of dermal melanocytes with no intervening connective tissue and the parallel theque pattern can be helpful in suggesting a diagnosis of nevoid melanoma at scanning magnification.

Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases.

BACKGROUND: Nevus sebaceus is commonly associated with the development of secondary neoplasms. Data on the frequency of malignant tumors vary considerably in published reports. OBJECTIVE: We sought to analyze the distribution of secondary neoplasm in nevus sebaceus. METHODS: A retrospective analysis of all cases of nevus sebaceus diagnosed at the Ackerman Academy of Dermatopathology from 1999 to 2012 was conducted. RESULTS: A total of 706 patients (707 specimens) were included in the study. Trichoblastoma was the most frequent benign tumor (n = 52, 7.4%) followed by syringocystadenoma papilliferum (n = 33, 5.2%). Malignant tumors were present in 2.5% of the specimens with basal cell carcinoma being the most common (n = 8, 1.1%) followed by squamous cell carcinoma (n = 4, 0.57%). The incidence of secondary neoplasms was statistically related to age and anatomic site (P < .05). Almost all malignant tumors were seen in adults. LIMITATION: Some of our cases were referred for second opinion and there may be a bias in our data toward unusual secondary neoplasms. CONCLUSION: Our study confirms that most of the secondary neoplasms arising in association with nevus sebaceus are benign. As no malignant tumors were seen in children, we believe it is reasonable to delay surgical management until adolescence.

Phosphohistone-H3 and Ki-67 immunostaining in cutaneous pilar leiomyoma and leiomyosarcoma (atypical intradermal smooth muscle neoplasm).

BACKGROUND: The mitotic index is important in the assessment of tumors such as leiomyoma (LM) and leiomyosarcoma (LMS), which may exhibit a range of cytological atypia. The mitotic marker phosphohistone-H3 (PHH3) was shown to improve interobserver and intraobserver variability in many tumors. MATERIALS AND METHODS: We evaluated the mitotic index in 20 pilar LM and cutaneous LMS using PHH3 and hematoxylin and eosin (H&E)-stained sections. Ki-67 staining characteristics of the tumors were also assessed. RESULTS: Mitotic figures were more easily identified within PHH3 sections. The mitotic index per 10 high power fields (HPF) on the PHH3 stain was slightly higher than H&E both in the LM (mean 0.1, range 0-1 vs. mean 0) and LMS groups (mean 8.6 vs. 8.0 with range of 1-24 for both stains). The difference in mitotic index between the two stains was not statistically significant in either group (p = 0.7). The Ki-67 proliferative index showed a statistically significant correlation with a diagnosis of LMS. CONCLUSION: PHH3 immunostain can simplify counting of mitotic figures in cutaneous smooth muscle neoplasms, especially those with many pyknotic nuclei, and may help to reduce interobserver variability. Ki-67 staining may also be of help in establishing a diagnosis of LMS.

Treatment of port-wine stains with a short pulse width 532-nm Nd:YAG laser.

BACKGROUND AND OBJECTIVE: Pulsed dye laser treatment often results in port-wine stain (PWS) improvement; however, results vary. A frequency-doubled neodymium-doped yttrium aluminum garnet (Nd:YAG) laser that allows for shorter pulse widths along with large spot sizes and high fluences has been developed for the treatment of cutaneous vascular lesions. STUDY DESIGN: A prospective, controlled study was performed in 5 adults with PWS using a frequency-doubled Nd:YAG laser (Excel V; Cutera Inc, Brisbane, CA) in 4 quadrants, using spot sizes of 6 to 10 mm, fluences of 4.8 to 9 J/cm2, and pulse durations of 3 to 6 ms. An adjacent control area was not treated. Each was assessed immediately posttreatment for purpura and edema and at 1 month for PWS color, size, texture, and thickness. Skin biopsies obtained immediately after and at 1 month posttreatment were evaluated. RESULTS: All treatment quadrants displayed purpura. At 1-month follow-up, all treatment quadrants showed at least 1 grade of color improvement, from a minimum of 1% to 25% to a maximum of 51% to 75% improvement (12/20 quadrants with 1%-25% improvement, 3/20 with 26%-50%, 5/20 with 51%-75%, and 0/20 with 76%-100%). Histologic evaluation of treatment quadrants revealed vascular changes ranging 0.35 to 4 mm in depth. Immediately posttreatment, thrombi and extravasated red blood cells were observed in treatment quadrants. Histology at 1 month revealed decreased number and diameter of vessels in treatment quadrants (superficial vessels decreased by mean 1.1 vessels per section [13%], and diameter by 3.0 µm [47%], midlevel vessels decreased in number by 2.3 [20%], diameter by 2.42 µm [25%], and deep vessels decreased in number by 1.5 [83%], and diameter by 7.44 µm [88%]). CONCLUSIONS: A single treatment with a short pulse width, frequency-doubled Nd:YAG laser resulted in safe and effective improvement of PWS, with up to 75% improvement in color observed at 1 month. Histologic evaluation demonstrated vascular injury at depths of 0.35 to 4 mm with a reduction in vessel number and size at multiple dermal levels.

The diagnostic value of fungal fluorescence in onychomycosis.

BACKGROUND: Fluorescence of pathogenic fungi has been previously shown when hematoxylin and eosin-stained sections are examined under a fluorescent microscope. We hypothesize that this phenomenon could aid in the evaluation of nail specimens for onychomycosis. METHODS: Forty-eight routinely stained nail sections of periodic acid-Schiff (PAS)-positive onychomycosis, along with 23 PAS-negative control specimens with a clinical diagnosis of onychomycosis, were studied under a fluorescent microscope to determine the clinical usefulness of this technique. RESULTS: In most cases, fluorescence of fungal organisms was noted. Fungi were identified by their tubular or annular shapes with fluorescence surrounding them. The sensitivity and specificity of the method were 96 and 90%, respectively. In some cases, it was difficult to identify the fungi because of the relative paucity of organisms, weak fluorescence and high background fluorescence of eosinophilic nail keratin. CONCLUSIONS: We conclude that fluorescence microscopy can be used as a rapid screening tool for identification of fungi in nail specimens.

Epidermal panfolliculoma: an adnexal proliferation with advanced follicular differentiation confined to the epidermis.

Follicular differentiation can be exhibited by a variety of epidermal lesions. We report an example of panfolliculoma purely confined to the epidermis. The lesion presented as a verrucous plaque on the leg of a 55-year-old man. Histopathologic sections showed an acanthoma with follicular differentiation including areas mimicking the follicular germ, matrix, root sheath and infundibular components.

Melanoma masquerading as xanthogranuloma: a diagnostic pitfall.

Melanoma can present with protean combinations and permutations of histologic features mimicking a plethora of nonmelanocytic benign and malignant proliferations. Anecdotal cases of melanoma closely simulating fibrohistiocytic proliferations have been reported. At times, the reliable differentiation between melanoma and histiocytic proliferations could be vexing histopathologically. We report an unusual presentation of melanoma in an 87-year-old man strikingly resembling xanthogranuloma both clinically and histopathologically. Histologic sections revealed a diffuse proliferation of pleomorphic cells some with foamy cytoplasm and occasional Touton-like giant cells in the dermis accompanied by inflammatory cells. Rare single-cell pagetoid scatter was evident within the epidermis. The infiltrate had patchy staining on CD163, interpreted as part of the inflammatory component but the atypical cells stained heavily with Melan A and tyrosinase confirming the diagnosis of malignant melanoma. Our case demonstrates yet another face of malignant melanoma and the critical but judicious use of immunohistochemistry in reliably distinguishing between melanoma and histiocytic tumors.

Adult Langerhans cell histiocytosis in a middle aged Ethiopian woman.

Langerhans' cell histiocytosis represents a diverse group of rare disorders characterized by proliferation and infiltration of various organs by bone marrow-derived abnormal Langerhans' cells. These diorders exhibit varied patterns of organ involvement, age distribution, prognosis and clinical manifestation. Here in we discuss an adult presentation of the disease in a 43 years old lady and summarize the latest recommendations regarding the classification, pathogenesis, work up and treatment of adult patients with these disorders.