Periampullary Mass as an Unusual Manifestation of Coccidioidomycosis. Case Report and Literature Review

In Colombia, coccidioidomycosis is a rare entity, and the intestinal manifestation is infrequent, with around a dozen cases reported in the world literature. This article reports the case of a 29-year-old male Venezuelan immigrant with a 4-month history of abdominal pain, jaundice, nausea, and vomiting. The tomography and the endoscopic study revealed a circumferential exophytic mass in the second portion of the duodenum. The biopsy revealed multiple spherules filled with round fungal endospores with a final diagnosis of disseminated coccidioidomycosis. The patient was discharged before the final pathology report with fluconazole doses of 200 mg every other day and an order for outpatient magnetic resonance cholangiography for outpatient follow-up, which he has not attended.

La coccidioidomicosis en Colombia es una entidad infrecuente y la presentación intestinal es extremadamente rara, con alrededor de una docena de casos reportados en la literatura mundial. En el presente artículo se reporta el caso de un paciente inmigrante venezolano masculino de 29 años con historia de dolor abdominal, ictericia, náuseas y vómito de 4 meses de evolución. La tomografía y el estudio endoscópico evidenciaron una masa exofítica circunferencial en la segunda porción del duodeno. La biopsia reveló múltiples esférulas llenas de endosporas fúngicas redondas con diagnóstico final de coccidioidomicosis diseminada. El paciente fue dado de alta antes del reporte final anatomopatológico con dosis de fluconazol de 200 mg interdiario y orden de colangiorresonancia ambulatoria para control ambulatorio, mismo al cual no ha asistido.

Insuficiencia respiratoria en una paciente con síndrome de Sézary / Respiratory failure in a patient with Sézary syndrome

Paciente de 44 años de sexo femenino, sin ninguna enfermedad de base preexistente, con una historia de aproximadamente diez meses de presentar lesiones eritemato-descamativas pruriginosas inicialmente localizadas en extremidades inferiores y que luego se generalizaron en todo el cuerpo, asociándose a la pérdida de peso de aproximadamente 15 kg. El manejo inicial consistió en corticoides tópicos y antihistamínicos orales con poca respuesta clínica. Se inició el estudio por dermatología y se confirmó el diagnóstico inicial de neoplasia cutánea maligna de células T. Luego se realizó el frotis de médula ósea, en el que se identificaron células «cerebriformes¼ que confirmaron el diagnóstico de síndrome de Sézary. La paciente recibió esquema de quimioterapia ciclofosfamida, doxorrubicina, vincristina, etopósido y prednisona. La respuesta inicial fue favorable, con alta hospitalaria y seguimiento en la consulta externa. Transcurridos tres meses de tratamiento, la paciente consultó por episodio febril, tos productiva más distrés respiratorio asociado a estertores basales bilaterales, presentó insuficiencia respiratoria y durante la inducción a la ventilación mecánica sufrió un paro cardiorrespiratorio y falleció

44-year-old female patient, with no preexisting underlying disease, with a history of approximately ten months of presenting pruritic erythematous-desquamative lesions initially localized in the lower extremities and later generalized throughout the body, associated with weight loss of 15 kg. Treatment. Initial management consisted of topical corticosteroids and oral antihistamines with little clinical response. A dermatology wok-up was initiated, and the initial diagnosis of malignant T-cell neoplasm was confirmed. A bone marrow smear was performed, in which "cerebriform" cells were identified, confirming the diagnosis of Sézary syndrome. The patient received cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone chemotherapy. Outcome. The initial response was favorable, with hospital discharge and outpatient follow-up. After three months of treatment, the patient consulted for a febrile episode, productive cough plus respiratory distress associated with bilateral basal rales, presented respiratory failure, and during induction of mechanical ventilation suffered cardiorespiratory arrest and died.

Aspergilosis invasiva: definiciones, diagnóstico y tratamiento / Invasive aspergillosis: definitions, diagnosis, and treatment

Resumen La aspergilosis invasiva (AI) es una enfermedad grave y con alta mortalidad. Existen factores de riesgo y se describen brotes intrahospitalarios relacionados con construcciones. También se des cribe una entidad relacionada con la infección por COVID-19, conocida como aspergilosis pulmonar asociada a COVID-19 (APAC). Es de vital importancia implementar un tratamiento adecuado y precoz, especialmente en pacientes inmunocomprometidos y críticamente enfermos. El diagnóstico se basa en reconocer los factores predisponentes, la clínica, la obtención de imágenes, exámenes directos, cultivos, histopatología y biomarca dores como el galactomanano. La droga de elección es el voriconazol, pero se deben conocer las alternativas terapéuticas dada la creciente presencia de aislamientos resistentes.

Abstract Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been described. An entity related to COVID-19 infection, known as COVID-19 associated pulmonary aspergillosis (CAPA), has recently appeared. Early and appropriate treatment is of paramount importance, especially in immunocompromised and critically ill patients. Diagnosis is based on recognition of predisposing factors, clinical signs, imaging, direct examination, culture, histopathology, and biomarkers such as galactomannan. The drug of choice is voriconazole, but alternative therapies must be taken into account given the increasing presence of resistant isolates.

Querión Celso, dermatofitosis del cuero cabelludo infantil / Kerion Celsi, dermatophytosis of the scalp in young boy

Resumen Querión Celso es una micosis ocasionada por hongos dermatofitos que daña el cuero cabelludo principalmente a niños y en raras ocasiones a adultos. La forma de infección para los humanos proviene de los animales y del suelo y se relaciona con mala higiene personal, hacinamiento en las viviendas, condiciones de subdesarrollo y pobreza. Se presenta un caso de un niño de 9 años con una úlcera de 7 cm de diámetro en el cuero cabelludo y en forma de placa circular que presentaba material purulento, pelo quebradizo y un área alopécica. Al inicio, se abordó de manera terapéutica como una infección bacteriana; posteriormente, se solicitó estudio micológico que evidenció una coinfección por el microorganismo Microsporum gypseum. Se le confirmó el diagnóstico de tiña capitis con afección inflamatoria y se le prescribió griseofulvina, lo que resultó en una curación completa.

Abstract Kerion Celsi is a mycosis caused by dermatophyte fungi that mostly affects children and rarely adults, causing damage to the scalp. The form of infection for humans comes from animals and the soil. The infection is related to poor personal hygiene, overcrowded homes, underdeveloped conditions, and poverty. A case of a 9-year-old boy with a 7cm diameter ulcer on the scalp and in the form of a circular plaque that presented purulent material, brittle hair and an alopecic area is presented. Initially it was therapeutically addressed as a bacterial infection, a mycological study was requested, which showed coinfection by the microorganism Microsporum gypseum, the diagnosis of tinea capitis with inflammatory condition was confirmed, and Griseofulvin was prescribed, resulting in complete cure.

Retrospective analysis of 77 pathologically confirmed cases of pulmonary mycosis in a hospital in the south Sichuan Basin, 2014-2021 / 中国热带医学

@#Abstract: Objective To observe the etiological distribution, basic information, clinical characteristics, imaging and pathological features, treatment regimens, and prognosis of pathologically confirmed cases of pulmonary mycosis, aiming to improve the diagnosis and treatment level of pulmonary mycosis. Methods The clinical, imaging and pathological data of patients with pulmonary mycosis diagnosed by pathological biopsy in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2021 were retrospectively analyzed. Results There were 77 cases of pulmonary mycosis who were diagnosed by pathology, and of these patients, 42 cases (54.54%) suffered from pulmonary aspergillosis, 34 cases (44.16%) suffered from pulmonary cryptococcosis, and 1 case (1.30%) suffered from pulmonary mucormycosis. Among the 77 patients, there were 38 male and 39 female patients, with an age range of 25 to 68 years old (mean age 51.13±10.32 years old). The common respiratory symptoms on admission included cough (33 cases, 42.86%), hemoptysis (24 cases, 31.17%), expectoration (22 cases, 28.57%) and chest pain (13 cases, 16.88%). Chest imaging features mainly included pulmonary nodules (37 cases, 48.05%), cavity (14 cases, 18.18%) and air crescent sign (10 cases, 12.99%). In this study, the main treatment measures for pulmonary mycosis were surgical resection (47 cases, 61.04%) and antifungal therapy combined with surgical resection (19 cases, 24.68%). After active treatments, most of these patients (72/77, 93.51%) discharged with better condition. Conclusions Pulmonary aspergillosis and pulmonary cryptococcosis are common pulmonary mycosis diagnosed by pathology. The main respiratory symptoms on admission are cough, expectoration and hemoptysis. Pulmonary nodules are the most common imaging features, and "air crescent sign" can be seen in some patients with pulmonary aspergillosis. Most pulmonary mycosis can have good treatment outcomes. Combining fungal histopathological characteristics and fungal special staining such as Periodic Acid-Schiff (PAS) staining and Gomori methenamine silver (GMS) staining can identify most pathogenic fungi into genera, which has important clinical significance for the timely diagnosis and treatment of pulmonary mycosis

Expert Guidelines for the Diagnosis, Treatment, and Management of Mycosis Fungoides in China / 罕见病研究

@#Mycosis fungoides (MF) is a cutaneous lymphoma originating from memory helper T cells. The lesion caused by classical type of MF is characterized by the progression from patches at early stages, advancing to more infiltrated plaques and eventually to tumors or erythroderma. Lymph nodes and visceral organs may be involved. The clinical course can last for decades. Early diagnosis of MF is difficult, usually requiring regular follow-up, repeated skin biopsy, and comprehensive analysis of the clinical manifestations, and involving histopathology, immunophenotype, and molecular biology. The treatment of MF should be determined on the stage of the disease. Patients with early-stage MF should be treated with skin-directed therapy, such as topical drugs, phototherapy, and radiotherapy. Advanced-stage MF or recurrent and refractory early-stage MF needs systemic treatments which can be combined with skin-directed treatment to alleviate symptoms. Multidisciplinary treatment (MDT) model is important for the management of patients with MF. The MDT team should conduct an overall evaluation of the patients when formulating the treatment plan, fully weighing the possible benefits, patient tolerance and side effects of treatment, so as to delay the progress of the disease and improve the quality of life of patients. With reference to the latest international and national research data, combined with the true state of China and expert experience, we developed the guidelines to standardize the process of diagnosis, treatment, and management of MF in China.

Concept of Cutaneous T Cell Lymphoma in Ayurveda Perspective and its Management by Sodhana, Samana and Rasayana: A Review Article

Cutaneous T cell lymphoma (CTCL) are a rare group of diseases caused by uncontrolled proliferation of T cells which belongs to mature T cell lymphoma having indolent nature. Two thirds of the CTCL are comprised of Mycosis Fungoides (MF) and Sezary Syndrome (SS). They are characterized by macules and patches which on later progresses to tumors or nodules with adenopathy and other organ infiltration. If left untreated the risk of developing infection increases with visceral involvement of skin, GI tract, lungs and adrenals. Diagnosis is done by histopathological appearance, cytogenetic analysis, etiology and the functional biology of neoplastic cells. Imaging techniques (MRI and CT) are widely done to assess the staging of disease and other tissue involvement. Radiotherapy, chemotherapy and retinoids have been in use since long time, but possess many side effects. According to Ayurveda, CTCL can be caused by Ahara like Virudha, Agantuja bhavas, Beeja-beejabhaga-beejabhagavayava dushti and Ojas/bala hani. The clinical features can be related with Kushta and in later stage simulates Dhatugata kushta and Granthi-arbuda. The etiopathogenesis of CTCL can be considered as formation of Ama, Agnimandhya, Srothovaigunya, and Balahani. Management will be preventive, curative and palliative with Sodhana, Samana and Rasayana therapies

CD8+ Mycosis Fungoides in Peripheral Blood; A Rare Finding

Cutaneous T cell lymphomas are mature lymphomas of T lymphocyte presenting with skin lesions and/or systemic manifestations. Majority of these cases show CD4+ phenotype and are classified as Mycosis Fungoides (MF)/Sezary syndrome (SS) spectrum.Here we present a case of 74-year-old male patient, having no known comorbid, presented in Dr. Ziauddin Hospital, Karachi OPD with complains of generalized skin lesions, itching for 2 years, generalized weakness for 4 months and no lymphadenopathy or visceromegaly. CBC showed absolute lymphocytosis and absolute eosinophilia. Some lymphocytes exhibited cerebriform nuclei. CT scan neck, chest and abdomen showed bilateral enlarged superficial inguinal lymph nodes and multiple enlarged bilateral axillary lymph nodes. Skin biopsy was inconclusive. Immunophenotyping of peripheral blood was then performed which showed an aberrant T cell population showing positivity for CD3, CD8, CD2, CD25 and negative for CD4, CD45, CD5, CD30, CD56 with variable expression of CD7. Case was finalized as CD8+ Mycosis Fungoides with peripheral blood involvement.These findings are very rare and highlight the importance of integrated approach to clinical course, morphological findings and other ancillary tests to be used in correlation with each other. These findings also highlight the diversity present in T cell malignancies in terms of immunophenotype.

SPECTRUM OF SUPERFICIAL MYCOSIS IN A TERTIARY CARE HOSPITAL- A MATTER OF CONCERN

BACKGROUND : Superficial mycosis has been recognized as a common fungal condition worldwide, including India. It refers to fungal infection of skin and its appendages. AIM & OBJECTIVES : 1) To determine the frequency of fungal agents isolated from clinically suspected cases of superficial mycoses, in a tertiary health care hospital. 2) To access the risk factors associated with it. 3) To analyse the demographic profile associated with superficial mycosis. MATERIAL & METHODS: The prospective study was carried out, over a period of 12 months (January 2021 to December 2021), samples such as skin scarping, hair plugs and nail clipping obtained from patients were submitted to Department of Microbiology for the fungal etiology. Samples were subjected to direct microscopy by KOH mount and fungal culture as per standard convectional technique. RESULTS: A total of 63 clinically suspected cases of superficial mycosis were enrolled in the study. Among the isolates recovered the most common were Dermatophytes(41.26%) followed by Candida(14.28%), Aspergillus(6.3%), Mucor(3.1%) and remaining 23.80% were sterile. Among the Dermatophytes, T.rubrum 42.30% was the predominant pathogen followed by T.mentagrophytes 34.61%. The most common age group affected was 21-40 years of age with male predominance of male to female ratio of 1.5:1. Out of total of 48 samples of superficial mycosis 26 were positive by direct microscopy and 48 samples were positive both by microscopy and culture. Most of the positive cases were recovered from immunocompromised individuals suffering from diabetes (37.5%) followed by prolonged antibiotic therapy (25.02%), long steroid therapy (12.5%) and chemotherapeutic agents (10.41%). The cases were mainly seen in the months between April to July which correlates the infection with the humid season. CONCLUSION: The study pinpointed dermatophytes as the most common clinical pattern of superficial mycosis with a male predominance. Dermatophytic infection is one of the emerging fungal disease along with non dermatophytic molds, especially in immunocompromised individuals prompt treatment and management can herald the onset of ensuing complications, thereby limiting the morbidity and thus improving the quality of life.

Research progress on total skin irradiation using helical tomotherapy / 中华放射肿瘤学杂志

Cutaneous T-cell lymphomas are a relatively rare group of mature T-cell lymphomas mainly manifesting in the skin, and its common subtype is mycosis fungoides. Total skin electron irradiation is one of the important conventional treatment methods, but there are many disadvantages, such as uneven dose distribution, poor position repetition, and long treatment time, which affect the clinical efficacy and patient prognosis. With the emergence and gradual popularization of helical tomotherapy in recent years, more and more medical institutions are gradually expanding their applications in total skin irradiation due to their ability to treat ultra-long targets and achieve dose-sculpted distribution, aiming to further explore its good or bad, and confirm whether it can replace the traditional total skin electron irradiation. In this article, research progress on total skin irradiation using helical tomotherapy was reviewed, the development of treatment technology, clinical efficacy and current concerns and controversies were illustrated.

Clinicopathological characteristics and prognosis of mycosis fungoides: analyses of 34 cases / 白血病·淋巴瘤

Objective:To investigate the clinicopathological features and prognosis of mycosis fungoides.Methods:The clinical data of 34 patients with mycosis fungoides hospitalized in Liaoning Cancer Hospital from January 1996 to December 2016 were retrospectively analyzed. The clinicopathological characteristics and prognosis of the patients were summarized. The follow-up was up to June 2021. Kaplan-Meier method was used for survival analysis, and log-rank test was used to compare the overall survival (OS) of patients among different subgroups.Results:Among the 34 patients, 22 (64.7%) were male and 12 (35.3%) were female; the median onset age was 56.5 years (25-93 years). A total of 23 cases (67.6%) presented with the rash on the whole body, and the main manifestations of the rash in the tumor stage were tumor rupture (10 cases, 29.4%) and redness (7 cases, 20.6%); 20 cases (58.8%) were misdiagnosed at initial onset. In the terms of TNMB stage, 3 cases were at stage Ⅰ (8.8%), 11 cases were at stage Ⅱ(32.4%), 3 cases were at stage Ⅲ (8.8%), and 17 cases were at stage Ⅳ (50.0%); 17 cases (50.0%) had the lesions confined to the skin and 17 cases had distant metastasis. Among the patients with distant metastasis, 7 cases had visceral organs involvement, 5 cases had lymph nodes involvement, and 5 cases had bone marrow or peripheral blood involvement. There were 32 cases treated with first-line chemotherapy alone, 9 cases with radiotherapy alone, and 7 cases in combination with radiotherapy and chemotherapy. Among the 32 patients treated with first-line chemotherapy, 14 cases had complete remission (CR), 12 cases had partial remission (PR), and response rate (RR) was 81.3% (26 cases); among the 9 patients who received radiotherapy, 3 cases had CR, 5 cases had PR, and RR was 88.9% (8 /19). The median follow-up time was 142.5 months; until the last follow-up, 20 (58.8%) cases survived, 6 (17.6%) cases died and 8 (23.5%) cases lost the follow-up. Survival analysis showed that the median OS of the whole group was not reached. Compared with patients whose lesions were confined to the skin, patients with distant metastasis had poorer OS ( P = 0.039). Among patients with distant metastasis, those with lymph node involvement had better OS, followed by those with bone marrow or peripheral blood involvement, those with visceral organ involvement had the poorest OS ( P = 0.045). Conclusions:The clinical misdiagnosis rate of early-stage mycosis fungoides is high, and the diagnosis mainly depends on clinical, histological and pathological characteristics. Radiotherapy and chemotherapy have high efficiency for early-stage disease and the prognosis of patients with distant metastasis is poor. OS in patients with lymph node involvement is better than that in patients with bone marrow or peripheral blood involvement, and OS in patients with visceral organ involvement is the worst.

Cutaneous hypopigmented lymphoproliferative disorders: a clinicopathological study of 41 cases / 中华皮肤科杂志

Objective:To investigate clinicopathological features of hypopigmented mycosis fungoides (HMF) and hypopigmented interface T-cell dyscrasia (HITCD) .Methods:A total of 41 patients with cutaneous hypopigmented lymphoproliferative diseases, who had complete clinicopathological data, were collected from Department of Dermatology, the Third People′s Hospital of Hangzhou from January 2015 to September 2020, and the clinicopathological and immunophenotypic features were analyzed. Comparisons of normally distributed measurement data were carried out using t test, comparisons of categorical data using Chi-square test or Fisher′s exact test, and comparisons of ranked data between 2 groups using rank-sum test. Results:All of the 41 patients clinically presented with irregular hypopigmentation, some of which was accompanied by erythema or furfuraceous scales. In terms of pathological features, 21 patients showed infiltration and aggregation of atypical lymphoid cells in the epidermis, which was consistent with typical pathological features of mycosis fungoides, and they were diagnosed with HMF; 20 patients showed vacuolar degeneration of the basal layer, accompanied by infiltration of lymphoid cells and mild epidermotropism, and they were diagnosed with HITCD. All immune cells expressed T-cell phenotype, and epidermal lymphocytes expressed a CD8-dominated phenotype in 14 (67%) cases of HMF and 13 (65%) of HITCD. In the epidermis, the total number of lymphocytes was significantly higher in the HMF group than in the HITCD group ( t= 1.81, P= 0.012) ; in the dermis, the number of CD4 + lymphocytes and CD8 + lymphocytes, and the total number of lymphocytes were all significantly higher in the HMF group than in the HITCD group ( t= 2.64, 1.51, 2.60, P= 0.012, 0.002, 0.001, respectively) . All patients were treated with narrow-band ultraviolet B radiation. Among 34 patients who completed the follow-up, 30 achieved complete clearance of skin lesions without recurrence, including all patients with HITCD, and 4 with HMF achieved partial regression of the lesions. Conclusions:Compared with HMF, HITCD presents different pathological characteristics and benign biological behaviors. Thus, HITCD should be distinguished from HMF as an independent disease. Phototherapy alone is effective for the treatment of HITCD.

Significance of lysophosphatidic acid receptor 6 in the large-cell transformation of mycosis fungoides and its effect on the proliferation and apoptosis of cutaneous T-cell lymphoma cells / 中华皮肤科杂志

Objective:To determine lysophosphatidic acid receptor 6 (LPAR6) expression in patients with mycosis fungoides (MF) , a variant of cutaneous T-cell lymphoma (CTCL) , and to investigate its role and mechanism of action in the development and prognosis of CTCL.Methods:A total of 110 patients with confirmed MF were collected from Department of Dermatology, Peking University First Hospital from 2011 to 2020, including 24 with large-cell transformation (LCT) and 25 with non-large cell transformation (NLCT) in the discovery cohort, and 24 with LCT and 37 with NLCT in the validation cohort. RNA sequencing and RT-PCR were conducted to determine the LPAR6 expression in patients in the discovery cohort and validation cohort respectively. LPAR6 expression was compared between patients with LCT and those with NLCT, and its effect on the prognosis of patients was evaluated. Two LPAR6-overexpressing CTCL cell lines MyLa and Sz4 were constructed to evaluate the effect of LPAR6 overexpression on proliferative activity of MyLa and Sz4 cells, with the cells normally expressing LPAR6 as the control group; after the treatment with LPAR6-related ligand lysophosphatidic acid (LPA) , 2S-OMPT, adenosine triphosphate (ATP) or adenosine (ADO) , the effects of LPAR6 activation on the proliferative activity and apoptosis of LPAR6-overexpressing MyLa and Sz4 cells were evaluated by the MTS method and flow cytometry respectively. Log-rank test was used for prognostic analysis, and t test or Mann-Whitney U test was used for comparisons between two groups. Results:As RNA sequencing showed, LPAR6 was one of the significantly underexpressed genes in the LCT group in the discovery cohort; in the validation cohort, LPAR6 expression (median[ Q1, Q3]) was significantly lower in the LCT group (204.90[81.90, 512.70]) than in the NLCT group (809.40[417.50, 1 829.20], U= 242.00, P= 0.002) ; in the two cohorts, the underexpression of LPAR6 was significantly associated with increased risk of poor prognosis (both P < 0.01) . Cell proliferation assay showed no significant difference in the proliferative activity of MyLa or Sz4 cells between the LPAR6 overexpression group and control group at 0, 24, 48 and 72 hours during the experiment (all P > 0.05) ; 48 hours after activation of LPAR6 by LPA, 2S-OMPT, ATP and ADO in MyLa cells, the LPAR6 overexpression group showed significantly decreased cellular proliferative activity (1.38 ± 0.01, 1.04 ± 0.01, 1.09 ± 0.03, 1.23 ± 0.01, respectively) compared the control group (1.73 ± 0.04, 1.23 ± 0.01, 1.24 ± 0.01, 1.42 ± 0.03, t= 30.33, 18.38, 4.78, 5.75, respectively, all P < 0.05) , but significantly increased cell apoptosis rate (17.93% ± 0.88%, 17.75% ± 0.35%, 23.97% ± 0.57%, 31.44% ± 0.34%, respectively) compared the control group (3.98% ± 0.03%, 7.81% ± 0.59%, 11.95% ± 0.85%, 12.02% ± 0.48%, t= 15.93, 14.49, 11.74, 33.01, respectively, all P < 0.05) ; 48 hours after activation of LPAR6 by 2S-OMPT and ADO in Sz4 cells, compared with the control group, the LPAR6 overexpression group also showed significantly decreased cellular proliferative activity (2S-OMPT: 1.29 ± 0.04 vs. 1.48 ± 0.01; ADO: 1.27 ± 0.01 vs. 1.51 ± 0.02; both P < 0.05) , but significantly increased cell apoptosis rate (2S-OMPT: 41.70% ± 0.70% vs. 29.35% ± 0.55%; ADO: 37.05% ± 0.15% vs. 24.60% ± 1.00%; both P < 0.05) . Conclusions:LPAR6 was underexpressed in the patients with LCT, and its underexpression was significantly associated with increased risk of poor prognosis. In vitro activation of LPAR6 could inhibit the proliferation of CTCL cells and promote their apoptosis, suggesting that the decrease of LPAR6 expression may be one of the important mechanisms underlying disease progression in patients with LCT.

Clinicopathological and immunophenotypic analysis of 24 cases of transformed mycosis fungoides / 中华皮肤科杂志

Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.

Correlations between pruritus and CC chemokine ligand 17 in patients with mycosis fungoides / 中华皮肤科杂志

Objective:To investigate molecules involved in the occurrence of pruritus in patients with mycosis fungoides (MF) .Methods:Totally, 522 patients with MF were enrolled from Peking University First Hospital from October 2009 to August 2021, and the incidence of pruritus was calculated. The patients were grouped according to whether they suffered from pruritus or not. RNA sequencing data on biopsied skin lesions of 49 patients were analyzed to identify differentially expressed genes between patients with pruritus and those without; enzyme-linked immunosorbent assay and immunohistochemical techniques were performed to determine the protein expression of CC chemokine ligand 17 (CCL17) in serum samples from 88 MF patients, and in tissue samples from 81 MF patients, respectively; flow cytometry was conducted to detect markers for T lymphocyte activation and differentiation in peripheral blood samples from 46 MF patients to identify peripheral blood lymphocyte subsets associated with pruritus. Statistical analysis was carried out by using chi-square test, Mann-Whitney U test, and Spearman correlation analysis. Results:Among the 522 patients with MF, 305 were males and 217 were females; 347 were diagnosed with early-stage MF, and 175 with advanced MF. The incidence of pruritus was 67.2% (351/522) in the patients with MF, and significantly higher in the patients with advanced MF (81.7%, 143/175) than in those with early-stage MF (59.9%, 208/347; χ2 = 25.03, P < 0.001) . RNA sequencing showed that CCL17 mRNA expression was significantly higher in the MF patients with pruritus than in those without (fold change = 10.09, P < 0.001) . The serum CCL17 concentration was significantly elevated in the patients with pruritus (1 017.05[377.12, 4 831.80] pg/ml) compared with those without (361.66 [180.47, 500.08] pg/ml; Z = -4.57, P < 0.001) , and correlated with pruritus scores ( r = 0.57, P = 0.010) . In both early and advanced stages of MF, the serum CCL17 concentration was significantly higher in the patients with pruritus than in those without ( Z = -3.68, P < 0.001; Z = -2.54, P = 0.011, respectively) . Immunohistochemical staining revealed that there was no significant difference in the relative quantification value of CCL17 between the patients with pruritus and those without ( Z = -1.84, P = 0.066) . The percentage of CD3 +CD4 +CD26 -CCR4 + malignant T cells significantly increased in the MF patients with pruritus than in those without ( Z = -2.03, P = 0.043) , and was positively correlated with serum CCL17 concentrations ( r = 0.49, P < 0.001) . Conclusions:Both CCL17 mRNA expression in lesional tissues and serum CCL17 concentrations increased in MF patients with pruritus, and CCL17 was associated with the occurrence of pruritus. CCL17 may be involved in the occurrence of pruritus through the recruitment of CD3 +CD4 +CD26 -CCR4 + malignant T cells.

Lobomycosis: exuberant presentation with malignant transformation

Abstract Lobomycosis is a chronic granulomatous infection caused by the yeast Lacazia loboi, typically found in tropical and subtropical geographical areas. Transmission occurs through traumatic inoculation into the skin, especially in exposed areas, of men who work in contact with the soil. Lesions are restricted to the skin and subcutaneous tissue, with a keloid-like appearance in most cases. The occurrence of squamous cell carcinoma on skin lesions with a long evolution is well known; however, there are scarce reports of lobomycosis that developed into squamous cell carcinoma. The authors report a patient from the Brazilian Amazon region, with lobomycosis and carcinomatous degeneration, with an unfavorable outcome, due to late diagnosis.

Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Abstract Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.

Multifocal Pseudotumorous Form of Neuroparacoccidioidomycosis in an Immunocompetent Patient: A Clinicopathological Review Based on a Case Report

Neuroparacoccidiodimycosis (NPDM) is an uncommon granulomatous disease, which more frequently affects immunocompromised male patients over 30 years of age in the course of chronic lung disease. Paracoccidioides brasiliensis (PB) is an endemic fungus in Brazil, and grows as thick-walled yeast (with round to oval bodies) measuring 10 µm to 60 µm in diameter. Neuroparacoccidiodimycosi may develop many years after transmission and/or primary lung involvement. The authors describe a case of NPDM affecting a male patient, 52 years of age, farmer, heavy smoker, with clinical complaint of headache, asthenia, seizures, and prostration in the previous nine months. Upon physical examination, the patient presented regular general condition, without other relevant physical alterations. Computed tomography (CT) showed multiple bilateral pulmonary nodules associated to enlargement of the mediastinal lymph node. Magnetic resonance imaging (MRI) and CTscans of the central nervous system showed six heterogeneous nodular lesions compromising the frontal and parietal lobes, the largest one measuring 3.8 3.2 3.2 cm. The hypothesis of a neoplastic process compromising the lung and brain was considered. A biopsy of the mediastinal lymph node showed epithelioid granulomas, which exhibited round, thin-walled fungal structures in Grocott silver stain. The stereotactic biopsy of the frontal lesion was constituted by necrotic tissue admixed with some round to oval, thin-walled fungi measuring 10 µm to 60 µm, compatible with PB (identified on Grocott silver stain/confirmed in culture). The diagnosis of NPDM was then established. The employed therapeutic regimen was intravenous amphotericin B, itraconazole, and sulfamethoxazole-trimetropin. After ninety days of clinical follow-up, no episodes of seizures/neurological deficits were identified, and a marked decrease in the number and size of the lung and brain lesions were found.

Hombre de 18 años con síndrome verrugoso tropical: ¿leishmaniasis o esporotricosis? / An 18-year-old man with tropical verrucous syndrome: Leishmaniasis or sporotrichosis?

Resumen | El síndrome verrugoso tropical comprende condiciones cutáneas infecciosas, crónicas y granulomatosas que cursan con placas, nódulos o úlceras verrugosas, de ahí su nombre. Este síndrome incluye la cromoblastomicosis, la esporotricosis, la paracoccidioidomicosis, la lobomicosis, la leishmaniasis y la tuberculosis cutánea verrugosa, todas ellas enfermedades de amplia distribución en áreas tropicales y subtropicales. Sus diagnósticos pueden ser difíciles y confundirse entre sí, lo cual es más frecuente entre la esporotricosis y la leishmaniasis. Para distinguirlas se recurre a criterios clínicos y epidemiológicos, y a métodos diagnósticos como intradermorreacción, examen directo, biopsia, cultivo, inmunofluorescencia y PCR, algunos de los cuales no son de uso común. El diagnóstico preciso conduce al tratamiento adecuado. Se presenta el caso de un hombre de 18 años con extensas placas verrugosas en una rodilla, inicialmente interpretadas como leishmaniasis verrugosa por la clínica, la epidemiología y la biopsia. Se le trató con Glucantime® durante 20 días, pero no presentó mejoría, por lo que se tomó una nueva biopsia que también se interpretó como leishmaniasis cutánea. La revisión de ambas biopsias evidenció inflamación con granulomas abscedados y presencia de cuerpos asteroides esporotricósicos, que condujeron al diagnóstico de esporotricosis, el cual se confirmó luego con el cultivo del hongo. Las lesiones remitieron con la administración de itraconazol. La clínica y la epidemiología de la leishmaniasis y las de la esporotricosis pueden ser semejantes, por lo que la biopsia y los estudios de laboratorio son esenciales para establecer el diagnóstico. El cuerpo asteroide esporotricósico es patognomónico de esta entidad. Se revisaron los conceptos esenciales de estas condiciones y los criterios para diferenciarlas.

Abstract | The tropical verrucous syndrome includes infectious, chronic, and granulomatous skin conditions appearing with plaques, nodules, or ulcers with a warty surface which gives name to the syndrome. It includes forms of chromoblastomycosis, sporotrichosis, paracoccidioidomycosis, lobomycosis, leishmaniasis, and tuberculosis verrucosa cutis with ample distribution in tropical and subtropical areas. The diagnoses may be difficult and confused among them, especially between sporotrichosis and leishmaniasis. Clinical, epidemiologic, intradermal reactions, direct smears, skin biopsies, cultures, immunofluorescence, and PCR are used to differentiate them, although several of these methods are not commonly used. We present an 18-year-old man with extensive verrucous plaques in one knee interpreted by clinic, epidemiology, and biopsy as verrucous cutaneous leishmaniasis. He was treated with Glucantime® for 20 days without improvement. A new biopsy was made that was also interpreted as cutaneous leishmaniasis. The revision of both biopsies showed inflammation with abscessed granulomas and asteroid sporotrichotic bodies at the center of the granulomas that led to the diagnosis of sporotrichosis later confirmed by the fungus culture. The patient responded to the treatment with itraconazole. As clinical and epidemiological findings of leishmaniasis and sporotrichosis can be similar, skin biopsy and other paraclinical studies are necessary to establish a proper diagnosis. The asteroid sporotrichotic body is pathognomonic of this mycosis. We review here the essential concepts of leishmaniasis and sporotrichosis and the criteria to differentiate them.

Infecciones bacterianas y fúngicas asociadas a la COVID-19 / Bacterial and fungal infections associated with COVID-19

RESUMEN Se realizó un estudio descriptivo en el Hospital Universitario Clínico Quirúrgico Cmdte. «Manuel Fajardo Rivero¼, Santa Clara, Villa Clara, marzo - julio de 2020, con el objetivo de describir las infecciones bacterianas y fúngicas asociadas a la COVID-19. La población de estudio fue de 202 pacientes que permanecieron ingresados con diagnóstico confirmado de infección por SARS-CoV-2. Las variables de estudio fueron: edad, sexo, infección asociada, estado al egreso, microorganismos aislados y susceptibilidad antimicrobiana. El 7,9 % de los pacientes presentó una infección asociada; el 7,4 % falleció (la mayoría de las defunciones ocurrieron en los meses de marzo y abril, previo al establecimiento del protocolo definitivo de tratamiento de la COVID-19 en Cuba). El 60 % de los fallecidos presentaron una infección asociada. Escherichia coli fue el microorganismo más aislado. Es necesario establecer un protocolo de diagnóstico terapéutico para determinar las infecciones bacterianas y fúngicas asociadas al coronavirus.

ABSTRACT A descriptive study was carried out at "Cmdte. Manuel Fajardo Rivero" Clinical and Surgical University Hospital in Santa Clara, Villa Clara from March to July 2020, with the aim of describing bacterial and fungal infections associated with COVID-19. The study population consisted of 202 patients who remained hospitalized with a confirmed diagnosis of SARS-CoV-2 infection. Age, gender, associated infection, discharge status, isolated microorganisms, and antimicrobial susceptibility were the variables studied. The 7.9% of the patients had an associated infection; 7.4% died (most deaths occurred in March and April, prior to the establishment of the definitive protocol for the treatment of COVID-19 in Cuba). The 60% of the deceased patients had an associated infection. Escherichia coli was the most isolated microorganism. A diagnostic and therapeutic protocol is necessary to determine the bacterial and fungal infections associated with the coronavirus.