PD-L1 expression in sebaceous carcinomas.

BACKGROUND: Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option. METHODS: A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning. RESULTS: A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases. CONCLUSION: Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma.

BACKGROUND: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

Clinical, microscopic and molecular presentation in pediatric versus adult old world cutaneous Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) is an emerging uncontrolled tropical parasitic disease in endemic and nonendemic areas with a high prevalence in the pediatric age group. METHOD: A total of 382 individuals from Lebanon, Saudi Arabia, Pakistan, and Syria diagnosed with CL by punch biopsy/scrapings were grouped into adults (>18 years) and pediatrics (≤18 years). Data recorded included clinical features [number, location, type, size, and extensiveness (size larger than 3 cm, more than 5 lesions per patient, lesion present for more than 12 months, special types, disfiguring lesion or closeness to vital sensory organs) of lesions] and microscopic findings [Ridley's Parasitic Index and Ridley's Pattern]. In addition, molecular confirmation and speciation were performed. RESULTS: In comparison with adults, patients in the pediatric group (n = 158, 41.4%) showed significantly higher number of lesions, more facial involvement, and more extensive disease (P < .05). Microscopically, a more advanced Ridley's pattern was observed. The other variables did not show statistical difference between the two groups. CONCLUSION: Historically, CL has been known to be a neglected tropical disease of poverty and pediatric predilection. In our pediatric group, CL manifests with more extensive disease clinically mirrored by more advanced lesions microscopically.

A Patient With a Protuberant Fibro-Osseous Lesion of the Temporal Bone.

Protuberant fibro-osseous lesion of the temporal bone, otherwise known as "Bullough's lesion", is a rare, benign exophytic fibro-osseous tumor. In this brief report, we present a case of a 61-year-old woman with a history of a right-sided skull mass that had been increasing in size for approximately 6 years before presentation. Clinical, radiological and histological features are examined and discussed. We achieved excellent results with surgical resection, with no evidence of recurrence.

Fatal Visceral Leishmaniasis Caused by Leishmania infantum, Lebanon.

Visceral leishmaniasis, a fatal disease if not treated, is caused by Leishmania parasites. This disease might be overlooked in the Middle East because of limited awareness and low incidence. We report 5 patients who died of visceral leishmaniasis in Lebanon and make recommendations to improve faster diagnosis and treatment.

Old World Leishmaniasis: an ancient disease with nonstandardized microscopic and clinical classifications.

BACKGROUND: Microscopic and clinical classifications of cutaneous leishmania have been set in the 1980s. Since then, they have been used invariably. Lebanon, a nonendemic country, is suffering from a leishmaniasis epidemic because of the massive population influx from endemic Syria. DESIGN: Patients diagnosed and speciated with leishmania (n = 169) using molecular and microscopic analysis were studied. General demographic data, microscopic data [Ridley's pattern (RP), microscopic pattern, Parasitic Index (PI)] and clinical stage were documented. Clinical score was scored as: 1: inflammatory; 2: proliferative/reorganization; 3: healed phases. The three patterns were studied in comparison to the lesion age and PI. RESULTS: At low PI, the clinical score and microscopic pattern showed healing scores (scores 3 and 4, respectively). In contrast, RP showed variable distribution at low PI. The same pattern is noted when correlating the different patterns with high PI. In comparison to lesion age, none of the three patterns showed the predicted linear correlation with lesion progression. CONCLUSION: In the studied population, the previously adopted classifications did not correlate with the disease progression. Such findings may raise the possibility of evolving disease. The proposed clinical and microscopic patterns showed better correlation with the disease progression.

Head and neck cutaneous leishmania: clinical characteristics, microscopic features and molecular analysis in a cohort of 168 cases.

Lebanon, an underendemic area for cutaneous leishmania (CL), is suffering from a CL outbreak brought by the massive population influx from endemic Syria. CL affects mainly exposed areas; therefore, the head and neck (HN) region is highly susceptible. Individuals diagnosed and speciated with CL (n = 168) using molecular and microscopic analysis on punch biopsy/scrapings were studied. Clinical data, parasitic index (PI) and Ridley's Pattern (RP) were recorded. The HN was divided into 11 anatomic locations. Of 168 patients, 96 patients (57.1 %) had HN involvement and 72 (42.9 %) had no HN involvement. Lesions from the HN were significantly more common in younger patients and were more prone for ulceration, had larger size, higher PI and more advanced RP (p < 0.05). There was no difference in the anatomic distribution of lesions among age groups and genders in the HN group. The cheek area was the most HN involved location. Lesions were less commonly encountered in the veiled area in women. In the community we studied, HN is commonly involved by CL. Lesions with HN involvement were encountered more in pediatric age group and showed more extensive features.

Mandibular melanotic neuroectodermal tumor of infancy: a role for neoadjuvant chemotherapy.

Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a rare, locally aggressive neoplasm with a predilection for the head and neck area, most commonly occurring in the maxilla. The vast majority of treatment modalities for all cases of MNTI to date have involved surgical intervention only, with just 9.6 % involving some sort of chemotherapy, radiotherapy, or a combination of the prior mentioned modalities. There is very limited information available regarding the use of neoadjuvant chemotherapy, due to its rare nature. In this report, a 4 month old girl presented to our clinic with a chief complaint of a large oral mass of about 2.5 months in duration. Intraoral examination showed an oral mass arising from the lingual aspect of inferior alveolar ridge with extensive mandibular invasion. The patient received three cycles of vincristine, Adriamycin, and cyclophosphamide as neodajuvant therapy. Upon completion, the tumor had decreased significantly in size. The patient was then scheduled for surgery and underwent surgical resection of the tumor. We were able to obtain adequate shrinkage of the tumor to allow better resectability, easier surgical access and a more minimally invasive approach with no lip split and a smaller neck incision. In conclusion, we have reported an extremely rare case of MNTI of the mandible that was successfully treated with neoadjuvant chemotherapy and surgical resection. This approach was advantageous to minimize the chance of recurrence and improve resectability in particularly large tumors, while maximizing functional outcomes and minimizing deformity.

Ongoing epidemic of cutaneous leishmaniasis among Syrian refugees, Lebanon.

In September 2012, a cutaneous leishmaniasis outbreak began among Syrian refugees in Lebanon. For 948 patients in whom leishmaniasis was not confirmed, we obtained samples for microscopic confirmation and molecular speciation. We identified Leishmania tropica in 85% and L. major in 15% of patients. After 3 months of megulamine antimonite therapy, patients initial cure rate was 82%.

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.

BRAF analysis on a spectrum of melanocytic neoplasms: an epidemiological study across differing UV regions.

BRAF mutation has been linked to the development of melanocytic tumors in homogeneous Caucasian cohorts. The role of solar UV radiation (UVR) in BRAF mutation status is poorly understood. We studied the epidemiology of BRAF mutation across a spectrum of melanocytic neoplasms in populations with differing UVR rates. Extended testing for 9 mutation types was attempted on 600 melanocytic neoplasms including banal nevi (n = 225), dysplastic nevi (n = 113), primary (n = 172), and metastatic melanomas (n = 90). Specimens were collected from 4 countries with increasing UVR rates (in kJ/m/yr): Syria (n = 45; UVR = 93.5), Lebanon (n = 225; UVR = 110), Pakistan (n = 122; UVR = 128), and Saudi Arabia (n = 208; UVR = 139). UVR was estimated from 21-year averages from The National Center for Atmospheric Research database. The overall BRAF mutation rate was 49% (268 of 545) and differed significantly by the geographic location [34% Pakistan, 49% Lebanon, 67% Syria, and 54% Saudi Arabia; P = 0.001], neoplasm type (P < 0.001), and anatomical location (P < 0.001) but not with age (P = 0.07) and gender (P = 1.0). V600E was the predominant mutation type, found in 96.3% of the cases. Incidence of melanoma was significantly greater in BRAF-negative (39%) versus BRAF-positive (17%) groups. For BRAF-positive cases, less severe lesions were systematically more frequent (P < 0.001). Multivariate analysis indicated that BRAF mutation is predicted by neoplasm type, anatomical site, and geographic location. In our Near East cohort, BRAF mutation rates varied by geographic location but not based on UVR. BRAF-positive status was associated with less severe lesions.

Predictors of BRAF mutation in melanocytic nevi: analysis across regions with different UV radiation exposure.

BACKGROUND: BRAF mutations have been implicated in initiating promutagenic cellular melanocytic proliferation mostly based on homogeneous Western-based cohorts. Data addressing the possible interaction between exposure to different solar ultraviolet radiation (UVR) magnitudes and BRAF mutation rate (BMR) in melanocytic nevi are limited. DESIGN: Extended BRAF testing for 9 mutations in 225 melanocytic nevus (MN) cases derived from 211 patients from 4 different UVR regions: Lebanon (n = 95; 110 kJ · m(-2) · yr), Syria (n = 23; 93.5 kJ · m(-2) · yr), Kingdom of Saudi Arabia (n = 70; 139 kJ · m(-2) · yr), and Pakistan (n = 37; 118 kJ · m(-2) · yr) was performed. Data collected included age, gender, anatomic location, and lesion size. Histological parameters recorded were MN type (junctional, compound, intradermal, classical blue, cellular blue, compound and intradermal spitz, and congenital) solar elastosis grade, and nevus pigmentation degree. Cumulative 21-year erythemally effective UV averages were derived from The National Center for Atmospheric Research. RESULTS: BRAF mutation status was obtained in 210 cases (6.7% failed polymerase chain reaction). Overall, BMR was 62.4% (131/210) with V600E mutation accounting for 98.5% of cases. Discordant mutation status was found in 2 of 10 patients with multiple nevi. BMR differed significantly, yet nonsystematically, among UVR regions; the highest was detected in nevi coming from Syria (18/23 cases, 78%), followed by Pakistan (21/30 cases, 70%), Kingdom of Saudi Arabia (47/70 cases, 67%), and Lebanon (45/87 cases, 52%). Mutation rates varied significantly across MN type (P < 0.001); the highest rate was recorded in the intradermal nevus type (33/39 cases, 84.6%), followed by the compound (26/32 cases, 81.2%) and congenital (60/74 cases 81.0%) nevi. Stratified by anatomic location, nevi occurring on the face (61/82, 74%) and trunk (58/78, 74%) had more frequent BMRs compared with those occurring on the upper (7/26, 27%) and lower extremities (5/24, 21%, P < 0.001). Severe pigmentation was less frequent in BRAF mutation-positive nevi [5/131 (4%) vs. 34/79 (43%); P < 0.001]. Multivariate independent predictors of BRAF mutation in MN were age [odds ratio (95% confidence interval ) = 1.43 (1.13-1.74) per 10 years; P = 0.004], anatomic location [P = 0.043 overall], and nevus type [P < 0.001 overall]. UVR region was not an independent predictor of BRAF mutation. CONCLUSIONS: Increased BRAF mutation with age along with the lack of a UVR magnitude-BRAF mutation association suggests that duration of exposure rather than UVR exposure dose is the more likely link to acquiring the mutation.

Solitary fibrous tumors of the kidneys: presentation, evaluation, and treatment.

INTRODUCTION: Renal solitary fibrous tumors (SFTs) are spindle cell neoplasms of mesenchymal origin, and very rare with only 46 cases reported worldwide to date. It is crucial to differentiate this tumor from other tumors of the kidney, so as to avoid unnecessary treatment. Therefore, our objective was to review reports of renal SFTs, their clinical presentations, imaging methods, and surgical management, updated to 2013. MATERIAL AND METHODS: We retrospectively reviewed articles published in the USA, Europe, and Asia from 1996 to date using PubMed, Medscape, Medline, and several major journals. We report on areas of controversy and well-established guidelines. RESULTS: We reviewed 58 articles which confirmed, with a high level of evidence-based medicine, that the male-to-female ratio is equal and their most common presentation is an incidental finding on a radiological study, in which it is difficult to differentiate them from renal cell carcinoma. Nephrectomy is the gold standard treatment, with almost no recurrence. CONCLUSIONS: In symptomatic patients, complete surgical resection of renal SFTs may provide a very good outcome, with almost no recurrence.

Loss of KLK4::KLKP1 pseudogene expression by RNA chromogenic in-situ hybridization is associated with PTEN loss and increased risk of biochemical recurrence in a cohort of middle eastern men with prostate cancer.

BACKGROUND: KLK4::KLKP1 fusion is a recently described pseudogene that is enriched in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern population. OBJECTIVE: To establish the incidence and prognostic value of KLK4::KLKP1 fusion in a cohort of Middle Eastern men with PCa and explore the relationship of this marker to other relevant biomarkers (PTEN, ERG, SPINK1). DESIGN, SETTING, AND PARTICIPANTS: We interrogated a cohort of 340 Middle Eastern men with localized PCa treated by radical prostatectomy between 2005 and 2015. KLK4::KLKP1 fusion status was assessed by RNA Chromogenic in situ hybridization (CISH) and correlated to pathological and clinical parameters. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA-CISH expression of KLK4::KLKP1 was correlated with prognostic factors, ERG, PTEN, and SPINK1 expression, and biochemical recurrence (BCR) following prostatectomy. RESULTS AND LIMITATIONS: 51.7% of patient samples showed positive KLK4::KLKP1 expression; more commonly in cores of PCa (38%) versus non-cancer (20.6%) (p < 0.0001) and in lower Gleason Grade Group tumors (1-3) vs (4-5). KLK4::KLKP1 expression positively correlated with ERG positivity and inversely associated with PTEN loss. No significant association was found with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (< 50 or ≥ 50). The association between PTEN loss and BCR increased when combined with KLK4::KLKP1 negativity (HR 2.31, CI 1.03-5.20, p = 0.042). CONCLUSIONS: KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.

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

AIMS: Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple-negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas. METHODS AND RESULTS: Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and 'basal' markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development. CONCLUSIONS: Our results support the contention that MGA can be a clonal lesion and non-obligate precursor of triple-negative breast cancer.

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. METHODS: Skin biopsies (n = 212) with cutaneous leishmaniasis in Lebanon (n = 46), Syria (n = 53), Saudi Arabia (n = 45) and Pakistan (n = 68) were evaluated. Clinical data collected included age, gender, eruption type (papule, nodule, verrucous or scar), duration and anatomic location. Histopathologically, multiple parameters were recorded including Ridley's parasitic index and pattern, transepidermal elimination, interface changes, ulceration and necrosis. Transepidermal elimination was defined as the presence of amastigotes in the epidermis in all layers, limited to the basal layer or present in a perforating plug. All cases were confirmed by polymerase chain reaction (PCR) analysis followed by restriction fragment length polymorphism analysis for molecular subspeciation. RESULTS: Leishmania tropica was identified in 88.2% and Leishmania major in 11.8% of all cases. Transepidermal elimination was observed in 28.3% of cases (29 perforating plug, 19 all layers and 12 basal layer) with a significant prevalence of L. major in this group (35 vs. 2%, p < 0.001). Cases with transepidermal elimination were associated with interface changes and higher parasitic index (p < 0.001) but not with an increased ulceration rate (p > 0.05). Multivariate analysis showed that transepidermal elimination was independently predicted by L. major [OR (95% confidence interval) = 80 (9-712); p < 0.001], parasitic index [OR = 3.4 (2.1-5.3); p < 0.001], interface changes [OR = 6.24 (2.2-17.8); p < 0.001] and necrosis [OR = 0.2 (0.1-0.8);p = 0.026]. CONCLUSIONS: We report the largest multiregional cutaneous leishmaniasis series with a 28.3% documented transepidermal elimination incidence of which 48% were perforating plug; a significant prevalence of L. major was also identified in the transepidermal elimination group. The association of transepidermal elimination with interface changes and a higher parasitic index, without an increased ulceration rate, may reflect a unique biologic alteration in the epidermis, serving to facilitate the extrusion of the parasites through the skin.

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. METHODS: Skin biopsies from 122 patients from Lebanon, Syria and Saudi Arabia with clinical diagnosis of untreated leishmaniasis were reviewed and clinical data extracted. Cases were classified according to the modified Ridley's parasitic index. DNA was extracted from formalin-fixed paraffin-embedded blocks. Polymerase chain reaction (PCR) was performed using Leishmania-specific ribosomal internal transcribed spacer 1 (ITS1-PCR). Nested ITS1-PCR was performed on cases negative for conventional ITS1-PCR. ITS1-PCR amplicons were digested with HaeIII for subsequent restriction fragment length polymorphism (RFLP) subspeciation. RESULTS: Of 122 cases, 54 (44.3%) showed a parasitic index of 0-1+ (no unequivocal amastigotes). ITS1-PCR (conventional and nested) was positive for all cases as compared with negative control tissue. RFLP identified Leishmania tropica in all cases. Patients with clinically suspected leishmaniasis, whose skin biopsies failed to detect amastigotes represented 44.3% of our cases. CONCLUSIONS: In this study, we describe a rapid and optimized protocol from DNA extraction to leishmaniasis subspeciation. ITS1-PCR showed high sensitivity and specificity in confirming clinically suspected cases.

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. METHODS: The study was conducted on 145 skin biopsies from untreated patients with histopathological and/or clinical suspicion of cutaneous leishmaniasis in Lebanon, Syria and Saudi Arabia (1992-2010). The pre-biopsy clinical diagnosis and demographic data were collected. Biopsies were evaluated for the major microscopic pattern, and the parasitic index (PI) was also determined. Diagnosis was confirmed by polymerase chain reaction (PCR) followed by molecular sub-speciation. RESULTS: Of the 145 patients, 125 were confirmed as cutaneous leishmaniasis by PCR. Eighteen cases presented with a pre-biopsy clinical diagnosis other than cutaneous leishmaniasis that ranged from dermatitis to neoplasm. Of the 125 cases, 57 showed a major histopathological pattern other than cutaneous leishmaniasis. Identification of amastigotes was equivocal (PI ≤1) in 38 of the 57 cases. Of interest, all the 18 cases with a pre-biopsy clinical diagnosis other than cutaneous leishmaniasis also showed atypical histopathology for cutaneous leishmaniasis. CONCLUSIONS: The manifestations of cutaneous leishmaniasis are broad and may mimic other inflammatory and neoplastic diseases. Pathologists and dermatologists should be aware of such pitfalls and can utilize PCR to confirm the diagnosis of leishmaniasis.

Interpretive Errors in Fine-Needle Aspiration of Thyroid: A 13-Year Institutional Experience in Lebanon.

INTRODUCTION: Fine-needle aspiration (FNA) is a worldwide established diagnostic tool for the assessment of patients with thyroid nodules. All thyroid FNA interpretive errors (IEs) were reviewed at the American University of Beirut Medical Center over a 13-year period, in order to identify and analyze them. MATERIALS AND METHODS: All FNAs and their corresponding pathology results are correlated yearly for quality assurance. Discrepant cases are segregated into sampling errors and IEs. All thyroid FNAs with IEs were collected from 2005 to 2017. FNA and pathology slides were reviewed by trained, board-certified cytopathologists, adhering to the latest Bethesda criteria. Reasons for erroneous diagnoses were studied. RESULTS: There was a total of 11 IEs out of 340 thyroid FNAs followed by surgical resection. Five benign follicular nodules (BFNs) were misinterpreted as suspicious for carcinoma. Focal nuclear atypia in cyst-lining or follicular cells and a monotonous population of macrophages misinterpreted as Hurthle cells (HCs) were the causes of IEs in this category. Four Hashimoto's thyroiditis (HT) cases were misinterpreted as suspicious for malignancy. Innate atypia of HCs and sampling misinterpretation were the causes of IEs in HT. One medullary and 1 follicular carcinoma were misinterpreted as suspicious for follicular neoplasm and BFN, respectively. Nine cases were better classified after review. CONCLUSION: Thyroid FNA IEs can be mitigated by meticulous screening and identification of all elements on FNA smears. Awareness of focal nuclear atypia in reactive cyst-lining and follicular cells in BFN, as well as HCs in HT, is highlighted. Adherence to The Bethesda System for Reporting Thyroid Cytopathology and consulting experienced cytopathologists significantly decrease IEs.