Organomegalies as a predictive indicator of leukemia cutis in patients with acute myeloid leukemia.

BACKGROUND: Leukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC. MATERIALS AND METHODS: We conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses. RESULTS: The study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC). CONCLUSIONS: AML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.

The efficacy of UVA1 phototherapy in psoriasis: Clinical and histological aspects.

BACKGROUND: Although ultraviolet A1 (UVA1) phototherapy is available for nearly 30 years, only few studies have been conducted for plaque-type psoriasis. OBJECTIVES: To determine the efficacy and safety of UVA1 phototherapy in psoriasis by assessing the clinical and histological outcomes. METHODS: This open study enrolled 15 patients with moderate to severe plaque-type psoriasis. All of the patients had skin type IV. A whole-body UVA1 device consisting of 24 lamps, was irradiated at a medium dose of 50 J/cm2 three-times weekly for 30 sessions. Topical and systemic psoriasis treatments were discontinued before and during treatment; patients could only use emollients and antihistamines until 1-month post-completion. Psoriasis Area and Severity Index (PASI) scores were determined at baseline; at sessions 10th, 20th and 30th; and 1 month after treatment. Four-millimetre punch biopsies were obtained from the same psoriasis lesion at baseline and session 30th. Changes in histopathological gradings and polymorphonuclear, lymphocyte and Langerhans cell numbers were monitored. RESULTS: Twelve patients completed the study. The mean age was 41.3 years (range: 25-71). The median PASI scores at baseline, session 30th and 1-month post-treatment were 16 (8.2, 43.3), 11 (4.4, 43.3) and 9.2 (2.7, 36.4), respectively. Although the PASI scores had improved significantly by 1-month post-treatment (P = .006), the histological parameters demonstrated minimal changes. All patients tolerated the phototherapy well and the most common side effect was skin tanning. CONCLUSIONS: While medium-dose UVA1 phototherapy demonstrated some efficacy in moderate to severe plaque-type psoriasis. However, it might not be an excellent choice.

Cost-effectiveness analysis and safety of erythromycin 4% gel and 4% chlorhexidine scrub for pitted keratolysis treatment.

Background: Studies of Pitted keratolysis (PK) treatment are limited. Objectives: To study cost-effectiveness and to compare the safety of 4% chlorhexidine scrub with 4% erythromycin gel, for PK infections. Materials and methods: This cohort study was conducted on naval rating cadets with a clinical diagnosis of PK at Chumpol Naval Rating School, Thailand in 2016. Participants were randomly treated with either 4% erythromycin gel or 4% chlorhexidine scrub for 4 weeks. The clinical examinations were evaluated at the baseline and at 1 and 2 months after treatment. A decision-tree model was used to evaluate the costs, resource utilization and outcomes as quality-adjusted life-years (QALYs). Results: Of 344 naval rating cadets, 125 (36.3%) were diagnosed with PK. Sixty-four were treated with erythromycin. Approximately 80% of participants had complete resolution Foot odor were significantly improved at 2 months (p < .001) for both groups. No adverse effects were reported. Total cost for 4 weeks' treatment with the erythromycin gel and chlorhexidine scrub was US$77.34, US$51.9, respectively. Chlorhexidine treatment and erythromycin gel had 0.1526 and 0.1425 QALYs, respectively. Conclusions: treatment of PK with either 4% chlorhexidine scrub or 4% erythromycin gel had similar outcomes. However, using chlorhexidine scrub was more cost-effective.

Subcutaneous Panniculitis-Like T-Cell Lymphoma Versus Lupus Erythematosus Panniculitis: Distinction by Means of the Periadipocytic Cell Proliferation Index.

The distinction between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus (LE) panniculitis is remarkably challenging. Rimming by lymphocytes with an elevated Ki-67 cell proliferation index has been forwarded as a potential diagnostic finding in biopsies of SPTCL but has not been rigorously compared with biopsies from patients with LE panniculitis. Nineteen and 17 examples of SPTCL and LE panniculitis, respectively, were evaluated for periadipocytic rimming by lymphocytes expressing Ki-67, CD8, and ßF1 and for attributes associated with LE, including clusters of CD123-positive cells. The identification of periadiopocytic rimming using Ki-67, CD8, and ßF1 held sensitivity of 79%, 100%, and 89.5% and specificity of 100%, 52.9%, and 88.2%, respectively (P < 0.01). CD123-positive cells were in both disorders. LE-like histopathology was commonly encountered in SPTCL. In conclusion, an elevated Ki-67 cell proliferation index with rimming is useful for distinguishing SPTCL from LE panniculitis. Notably, many features of LE panniculitis can also be encountered in SPTCL.

Random skin biopsy in the diagnosis of intravascular lymphoma.

BACKGROUND: Random skin biopsy (RSB) is a method for diagnosis of intravascular lymphoma (IVL). However, the indications for RSB to diagnose IVL have not yet been established. The aim of this study was to determine the appropriate indications for RSB to diagnose IVL. METHODS: Thirty-two patients with fever of unknown origin (FUO) and without skin lesion underwent RSB for diagnosis of IVL. Clinical data, including fever, neurological symptoms, hematologic disorders, organomegaly, bone marrow (BM) study, hypoxemia and serum level of lactate dehydrogenase (LDH), were evaluated. RESULTS: Seven of 32 patients were definitively diagnosed with IVL. In addition to FUO, 2 IVL patients also suffered from dyspnea and neurological disorders. Patients who had FUO with accompanying hematologic disorders, high LDH, negative BM study and no lymphadenopathy or hepatosplenomegaly had a significant tendency to have IVL by RSB (P = .03). FUO with hypoxemia was also identified as a significant indication for RSB (P = .02). CONCLUSIONS: RSB is a reliable method for diagnosis of IVL, especially in patients with FUO and any 1 or more of the 4 following abnormalities: (1) hematologic abnormalities; (2) high serum LDH; (3) hypoxemia; and/or, (4) unusual neurological symptoms with co-existing hematologic abnormalities and without lymphadenopathy, hepatosplenomegaly or BM abnormality.

Immune response in human chromoblastomycosis and eumycetoma - focusing on human interleukin-17A, interferon-gamma, tumour necrosis factor-alpha, interleukin-1 beta and human beta-defensin-2.

Knowledge regarding host immune response to chromoblastomycosis and eumycetoma is limited, particularly concerning cytokines and antimicrobial peptides production. This was a retrospective study of 12 paraffin-embedded tissue samples from patients diagnosed with chromoblastomycosis or eumycetoma from histological findings and tissue culture. DNA extraction and polymerase chain reaction (PCR) from tissues were done to evaluate human interleukin-17A (IL-17A), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and human beta-defensin-2 (HBD-2) expressions. Human beta-actin primer was used for confirming DNA detection, and DNA extracted from psoriasis lesional skin samples was used as positive controls. The twelve paraffin-embedded sections used in this study consisted of five chromoblastomycosis and seven eumycetoma tissues. All PCR reactions showed beta-actin band at 51 bp in all clinical specimens, confirming adequate DNA levels in each reaction. As positive control, the psoriasis skin samples revealed bands for IL-17A at 174 bp, IFN-γ at 273 bp, TNF-α at 360 bp, IL-1ß at 276 bp and HBD-2 at 255 bp. For the chromoblastomycosis and eumycetoma tissues, PCR analyses showed IL-17A band at 174 bp in two eumycetoma tissues and HBD-2 band at 255 bp in a chromoblastomycosis tissue. This study demonstrated IL-17A expression in human eumycetoma and HBD-2 expression in human chromoblastomycosis for the first time. However, their role in immune response remains to be elucidated.

Thermal Response of In Vivo Human Skin to Fractional Radiofrequency Microneedle Device.

Background. Fractional radiofrequency microneedle system (FRMS) is a novel fractional skin resurfacing system. Data on thermal response to this fractional resurfacing technique is limited. Objectives. To investigate histologic response of in vivo human skin to varying energy settings and pulse stacking of a FRMS in dark-skinned subjects. Methods. Two female volunteers who were scheduled for abdominoplasty received treatment with a FRMS with varying energy settings at 6 time periods including 3 months, 1 month, 1 week, 3 days, 1 day, and the time immediately before abdominoplasty. Biopsy specimens were analyzed using hematoxylin and eosin (H&E), Verhoeff-Van Gieson (VVG), colloidal iron, and Fontana-Masson stain. Immunohistochemical study was performed by using Heat Shock Protein 70 (HSP70) antibody and collagen III monoclonal antibody. Results. The average depth of radiofrequency thermal zone (RFTZ) ranged from 100 to 300 µm, correlating with energy levels. Columns of cell necrosis and collagen denaturation followed by inflammatory response were initially demonstrated, with subsequent increasing of mucin at 1 and 3 months after treatment. Immunohistochemical study showed positive stain with HSP70. Conclusion. A single treatment with a FRMS using appropriate energy setting induces neocollagenesis. This wound healing response may serve as a mean to improve the appearance of photodamaged skin and atrophic scars.

Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by differentially expressed microRNAs.

IMPORTANCE: The molecular-genetic alterations contributing to the pathogenesis of sebaceous carcinoma and sebaceous adenoma remain poorly understood. Given that sebaceous carcinoma is associated with substantial morbidity and mortality, there is a critical need to delineate the pathways driving sebaceous carcinoma and candidate molecules for targeted therapy. OBJECTIVE: To describe differentially expressed microRNAs (miRNAs) in a series of periocular sebaceous carcinomas compared with sebaceous adenomas in order to identify pathways driving the pathogenesis of sebaceous carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Thirty sebaceous carcinomas and 23 sebaceous adenomas (including 11 that were confirmed to be related to Muir-Torre syndrome and 6 that were confirmed to be sporadic) were obtained from archives (from 48 patients) of 2 institutions (University of Texas MD Anderson Cancer Center, Houston, and Siriraj Hospital, Mahidol University, Bangkok, Thailand) and profiled. MAIN OUTCOMES AND MEASURES: Expression of miRNAs was determined using total RNA from formalin-fixed, paraffin-embedded tissue and real-time reverse transcription-polymerase chain reaction performed in a microfluidics card containing 378 unique miRNAs. Fold change was determined using the ΔΔCt method (reference probe, RNU48). Median centering was used to normalize the data. Two-sample t tests were used to identify differentially expressed miRNAs. The false discovery rate was assessed by ß-uniform mixture analysis of P values from the t statistics. Significance was defined by this estimated false discovery rate. RESULTS: Serial testing and validation confirmed overexpression of 2 miRNAs previously reported to be oncogenic, miR-486-5p (4.4-fold; P = 2.4 × 10-8) and miR-184 (3.5-fold; P = 1.7 × 10-6), in sebaceous carcinoma compared with sebaceous adenoma and downregulation of 2 miRNAs previously reported to have tumor-suppressive properties, miR-211 (-5.8-fold; P = 2.3 × 10-9) and miR-518d (-4.5-fold; 6.7 × 10-5), in sebaceous carcinoma compared with sebaceous adenoma. CONCLUSIONS AND RELEVANCE: Sebaceous carcinoma exhibits an miRNA expression profile distinct from that of sebaceous adenoma, implicating dysregulation of NF-κB and PTEN (targets of miR-486-5p) and TGF-ß signaling (target of miR-211) in the pathogenesis of sebaceous carcinoma. The identification of miRNAs whose expression is altered in sebaceous carcinoma compared with sebaceous adenoma provides a novel entry point for a more comprehensive understanding of the molecular-genetic alterations pivotal to the development of sebaceous carcinoma.

Tinea capitis caused by Trichophyton tonsurans presenting as an obscure patchy hair loss due to daily antifungal shampoo use.

Tinea capitis is unusual and often misdiagnosed in healthy adults. We report a case of a healthy woman with a several-year history of asymptomatic, bizarre-shaped, non-scarring alopecia. She had used over-the-counter ketoconazole shampoo regularly for a long time. An initial potassium hydroxide preparation showed negative result for fungal organism. The scalp biopsy revealed endothrix infection, and dermoscopic examination demonstrated the comma hair and corkscrew hair signs. The fungal culture showed Trichophyton tonsurans. The daily use of antifungal shampoo could be the important factor to conceal clinical and laboratory findings for diagnosis of T. tonsurans tinea capitis in our case, which required high clinical suspicion and histopathology and dermoscopic examinations.

Utility of BRAF V600E Immunohistochemistry Expression Pattern as a Surrogate of BRAF Mutation Status in 154 Patients with Advanced Melanoma.

Successful BRAF inhibitor therapy depends on the accurate assessment of the mutation status of the BRAF V600 residue in tissue samples. In melanoma, immunohistochemical (IHC) analysis with monoclonal anti-BRAF V600E has emerged as a sensitive and specific surrogate of BRAF V600E mutation, particularly when BRAF V600E protein expression is homogeneous and strong. A subset of melanomas exhibit heterogeneous labeling for BRAF V600E, but our understanding of the significance of heterogeneous BRAF V600E IHC expression is limited. We used next-generation sequencing to compare BRAF V600E IHC staining patterns in 154 melanomas: 79 BRAF(WT) and 75 BRAF (including 53 V600E) mutants. Agreement among dermatopathologists on tumor morphology, IHC expression, and intensity was excellent (ρ = 0.99). A predominantly epithelioid cell phenotype significantly correlated with the BRAF V600E mutation (P = .0085). Tumors demonstrating either heterogeneous or homogeneous IHC expression were significantly associated with the BRAF V600E mutation (P < .0001), as was increased intensity of staining (P < .0001). The positive predictive value was 98% for homogenous IHC expression compared with 70% for heterogeneous labeling. Inclusion of both heterogeneous and homogeneous BRAF V600E IHC expression as a positive test significantly improved IHC test sensitivity from 85% to 98%. However, this reduced BRAF V600E IHC test specificity from 99% to 96%. Cautious evaluation of heterogeneous BRAF V600E IHC expression is warranted and comparison with sequencing results is critical, given its reduced test specificity and positive predictive value for detecting the BRAF V600E mutation.

Emerging clinical applications of selected biomarkers in melanoma.

Melanoma is a lethal skin disease with a mostly predictable clinical course according to a known constellation of clinical and pathologic features. The distinction of melanoma from benign melanocytic nevus is typically unequivocol; however, there is a subset of tumors known for its diagnostic challenges, development of late metastases, and difficulties in treatment. Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease. This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status. The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma.

BACKGROUND: High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC. METHODS: Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival. RESULTS: H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035; HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT. CONCLUSIONS: Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.

Melanocytic matricoma: two cases of a rare entity in women.

Melanocytic matricoma is a rare cutaneous adnexal tumor occurring in humans with only 13 cases reported in the literature. The typical lesion is a circumscribed pigmented nodule on sun-damaged skin. Most cases have occurred in elderly men. The tumor contains a mixed population of matrical cells, supramatrical cells, shadow or ghost cells, and dendritic melanocytes. We report two cases of melanocytic matricoma in two elderly women with unusual histopathological features such as cystic degeneration and focal granulomatous inflammation, which are considered to be atypical for this entity.

A case series of sarcoidosis with pulmonary involvement: various clinical and radiographic manifestations.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The disease is rare in East Asian populations. Patients have many clinical presentations and 90% of patients have pulmonary involvement. There are few reports in Thailand that collected the data about chest imaging and pathological findings of sarcoidosis. MATERIAL AND METHOD: The data of patient with sarcoidosis with pulmonary involvement, who followed-up between September 2008 and December 2011, were retrospectively reviewed. RESULTS: Ten patients with sarcoidosis and pulmonary involvement were reviewed. Three patients presented with abnormal chest x-ray without respiratory symptom or other organ involvement. One patient was suspected to be sarcoidosis secondary to etanercept therapy. The majority of patients had cutaneous involvement. The most common finding on chest x-ray is bilateral hilar lymphadenopathy (90%). Seven patients had stage 2 disease and three patients had stage 1 disease. The diagnoses of all patients were confirmed by histopathology and exclusion of tuberculosis and fungal infection. Spirometry showed normal in seven patients, irreversible obstruction in one patient, and impaired diffusing capacity in six patients. There was no indication of systemic corticosteroids or immunosuppressive drug in most patients. CONCLUSION: Sarcoidosis has various clinical manifestations. The pulmonary and cutaneous involvement is common and the diagnosis is made by a combination of clinical, radiological, and histopathologic findings. The treatment of systemic corticosteroids is not required in most patients. The patients should be regularly followed-up in order to follow the course of disease.

Generalized granuloma annulare presenting with lesions resembling eruptive xanthoma.

Generalized granuloma annulare (GGA) and eruptive xanthoma are dermatological diseases that occasionally share some clinical and histological similarities. Associated underlying medical conditions and clinical course are essential guides to the proper diagnosis. The authors reported a case ofdisseminatedyellowish-redpapules in a 24-year-old female with high levels of serum fasting blood sugar triglycerides, and cholesterol. The provisional diagnosis was eruptive xanthoma but histopathology and immunoperoxidase study revealed granuloma annulare. The remission of the skin lesions soon after control of dyslipidemia and diabetes mellitus is not typical for the usual GGA, which has a chronic relapsing course and a poor response to treatment. Further studies are required to differentiate these two entities when they come into the clinicopathological mimicry.

Tender cutaneous nodules of the legs: diagnosis and clinical clues to diagnosis.

BACKGROUND: "Tender cutaneous nodules of the legs" is a common manifestation in dermatology. Histopathological investigation is usually required for this condition, because clinical data are frequently insufficient to make a definite diagnosis. OBJECTIVE: To identify and analyze the causes of patients presenting with tender leg nodules and to reveal clinical clues that could help to differentiate causes. MATERIALS AND METHODS: The medical records and histopathological slides of patients presenting with tender cutaneous nodules of the legs between January 2005 and December 2007 were retrospectively reviewed. RESULTS: Of the total of 154 patients, 122 (79.2%) were female. Definite diagnoses were categorized into four groups: inflammation (84.4%); infection (5.8%); tumor (6.5%); and nonspecific (3.2%). The most common cause in the inflammation group was erythema nodosum. The infections found were Acremonium spp., Penicillium sp., Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium leprae. The tumors included leiomyoma, leukemia cutis, and lymphomas. Clinical data that correlated with and could be used as clues for the inflammation group were female sex (P = 0.03, OR 6.43) and lower leg involvement (P = 0.03, OR 7.14). LIMITATIONS: The retrospective manner of this study is a limitation. CONCLUSION: Various inflammatory conditions, infections, and tumors can present as tender cutaneous nodules of the legs. Female sex and lower leg involvement were clinical data that could be used as clues for the diagnoses in the inflammation group. However, histopathological investigation is still crucial to determine a definite diagnosis in patients presenting with tender cutaneous nodules of the legs.

Mycobacterium fortuitum cutaneous infection from amateur tattoo.

A case of cutaneous Mycobacterium fortuitum infection after receiving an amateur tattoo is reported. A few days after tattooing, an otherwise healthy 25-year-old Thai male presented with multiple discrete erythematous papules confined to the tattoo area. He was initially treated with topical steroid and oral antihistamine without improvement. Skin biopsy was carried out, and the histopathology showed mixed cell granuloma with a foreign body reaction (tattoo color pigments). The acid-fast bacilli stain was positive. The tissue culture grew M. fortuitum two weeks later. He was treated with clarithromycin 1,000 mg/day and ciprofloxacin 1,000 mg/day for 10 months with complete response. From the clinical aspect, tattoo-associated rapidly growing mycobacterium infection might be difficult to differentiate from the pigment-based skin reactions. Skin biopsy for histopathology and tissue culture for Mycobacterium probably will be needed in arriving at the diagnosis.

Cutaneous anaplastic large cell lymphomas: a report of 9 cases from Thailand.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is one type of lymphoma, which is characterized by the proliferation of pleomorphic large atypical lymphoid cells expressing CD30 antigen. ALCL involving skin can be either primary cutaneous disease or cutaneous involvement secondary from systemic disease. Data of clinical manifestation of cutaneous ALCL in Thai patients is limited. ALCL in Thai patients may differ from other groups of patients. OBJECTIVE: To study the clinical manifestation of cutaneous ALCL in patients of Faculty of Medicine Siriraj Hospital, Thailand. MATERIAL AND METHOD: Medical records of nine patients with histopathologic diagnosis of ALCL from skin biopsy at Faculty of Medicine Siriraj Hospital were reviewed. RESULTS: Of nine patients, four patients were diagnosed as primary cutaneous ALCL, four patients as systemic ALCL with secondary skin involvement, and one patient as combined primary cutaneous ALCL and lymphomatoid papulosis. Three primary cutaneous ALCL patients had no recurrence of disease during 6-year follow-up. However all systemic ALCL patients died at one day to 1.5 years after diagnosis. CONCLUSION: Clinical manifestation and clinical course of Thai patients with anaplastic large cell lymphoma corresponded with the data from other patient population.