Ibrahim Khalifeh

Molecular diagnosis of cutaneous leishmaniasis and species identification: analysis of 122 biopsies with varied parasite index

Background: Cutaneous leishmaniasis is endemic in the Middle East and North Africa. Confirming the diagnosis histologically depends on amastigote identification, which varies significantly depending on the inoculum, strain type, host response and disease stage. Accurate histological diagnosis is mandatory for appropriate therapy.

Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis

Geyer F C, Lacroix‐Triki M, Colombo P‐E, Patani N, Gauthier A, Natrajan R, Lambros M B K, Khalifeh I, Albarracin C, Orru S, Marchiò C, Sapino A, Mackay A, Weigelt B, Schmitt F C, Wesseling J, Sneige N & Reis‐Filho J S

Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature.

Primary effusion lymphoma (PEL) is a rare aggressive subset of non-Hodgkin B-cell lymphoma. It is caused by Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8). It occurs mainly, but not exclusively, in HIV-positive patients. PEL predominantly develops in serous cavities and occasionally in extracavitary regions. PEL carries a very poor prognosis with a median survival time of <6 months. Indeed, currently used treatment modalities such as CHOP chemotherapy are far from achieving complete and sustainable remission. Therefore, there is no clear standard of care established in the treatment of PEL patients, stressing the need for novel-targeted approaches. Here, we have attempted a comprehensive assessment of the treatment of PEL, discussed avant-garde therapies and updated the state of preclinical research with promising clinical applications in the field. These include inhibitors of viral replication, modulators of cell signaling and inflammation, nuclear factor kappa B (NF-κB) and histone deacetylase inhibitors, and recently the combination of arsenic trioxide and interferon-alpha. Some of these targeted therapies have not yet reached clinical studies, although others were used in a few individual case reports with low numbers of patients. We also describe the first case of a 77-year-old, HIV-negative, HHV8-positive patient diagnosed with PEL limited to the pleural and peritoneal cavities. He received lenalidomide 25 mg/day for 21 days every 28 days. Treatment was well tolerated with no side effects. He rapidly improved after 1 month of treatment and progressively achieved complete remission persistent after 18 months of therapy. We believe that this review will bridge an important gap between classical chemotherapy and modern approaches of targeted therapy. Finally, our findings warrant further evaluation of lenalidomide in future prospective clinical studies.

Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases.

Background: Cutaneous leishmaniasis displays considerable variation in its histopathological and clinical presentation. Clinically, it progresses from a papule into a painless ulcerated and crusted nodule/papule. Microscopically, it progresses from sheets of amastigote‐filled histiocytes to granulomatous inflammation.

Transepidermal elimination in cutaneous leishmaniasis: a multiregional study

Background: Transepidermal elimination has been documented in a myriad of infectious diseases; however, its occurrence in cutaneous leishmaniasis has not been evaluated.

Comparing BRAF mutation status in matched primary and metastatic cutaneous melanomas: Implications on optimized targeted therapy

BACKGROUND Selective BRAF inhibitors have shown dramatic results with regard to improving outcome in patients with melanoma. Testing the BRAF status in matched primary and metastatic melanomas to optimize individual targeted therapy is not well investigated. METHODS Extended BRAF testing using PCR for 9 mutations and VE1 immunohistochemistry for BRAF V600E detection on 95 lesions including 40 primary melanomas with their matched metastases (n = 42), recurrences (n = 9) and second primaries (n = 4) was performed. Nine patients had multiple metastases. RESULTS V600E was the only identified mutation type; 35.4% of primary vs. 18.9% of metastatic melanomas. The overall primary-metastatic BRAF status discordance rate was 32.3% using PCR and 27.5% with immunohistochemistry, and was significantly more frequent in primary lesions with mutant BRAF (67%). Males and patients with metastasis to lymph nodes were less likely to be discordant compared to females and those with metastasis to other sites (p = 0.023). Discordant BRAF mutation status was predicted by multivariate binary logistic regression: the presence of a mutant BRAF in the primary melanoma [OR (95% C.I.) = 23.4 (2.4-229.7)] and female gender [OR = 10.6 (1.08-95)]. Inter-metastases BRAF concordance was 100% (6 comparisons). CONCLUSION A high discordant rate implies the need for clinical trials addressing the response to targeted therapy in patients with discordant BRAF statuses between their primary and metastatic lesions.

The immune microenvironment in cutaneous leishmaniasis.

Cutaneous leishmaniasis is an infection that has spread to non‐endemic regions, stimulating recent interest for the enhanced understanding of this disease. Downregulation of the CD1a receptor on Langerhans cells has been described in various cutaneous infections.

Cutaneous metastasis: clinicopathological study of 72 patients from a tertiary care center in Lebanon

Background  Cutaneous metastasis is the result of malignant cell spread from primary malignancy to the skin. This is not uncommon, and rates reported in the literature are as high as 10.4%. To the best of our knowledge, there are no studies assessing the epidemiologic, clinical, and histopathological features of cutaneous metastasis in our region.

Diagnosis of cutaneous leishmaniasis: why punch when you can scrape?

Cutaneous leishmaniasis (CL) has been introduced to the Leishmania under-endemic Lebanese population in an uncontrolled manner as a result of recent large-scale displacement of refugees from endemic Syria. Accordingly, a quick and reliable method to diagnose CL is essential. Matched punch biopsies and air-dried scrapings on 72 patients were obtained. Scrapings were collected in two forms: thick drop (N = 33) or thin smear (N = 39). Clinical information was recorded. Sections of punch biopsies and scrapings were stained and examined microscopically. Polymerase chain reaction (PCR) was performed on both scraping forms and biopsies. The diagnostic sensitivity of the tests performed revealed that microscopy in conjunction with PCR on punch biopsies was the most sensitive test (93%) overall. However, taken individually, microscopy and PCR yielded the highest sensitivities when performed on drop scrapings (63% and 85%, respectively), and not smear scrapings (38% and 56%, respectively) as compared with the punch biopsies (44% and 83%, respectively). Microscopic concordance for punch biopsies and drop scrapings was present in 25 of 33 cases. Concordance was predicted only by the high/low parasitic index (PI: 3.1 ± 1.7 and 0.4 ± 0.5, respectively; P < 0.05). Herein, we optimized a novel rapid method for reliable diagnosis of CL based on drop scrapings with good agreement with the gold standard punch biopsy technique.

BRAF mutational epidemiology in dysplastic nevi: Does different solar UV radiation exposure matter?

Proto‐oncogene B‐Raf (BRAF) mutation rates have been reported in nevi and melanomas of homogeneous Caucasian cohorts.