The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer.

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

TIROSEC: Molecular, Clinical and Histopathological Profile of Papillary Thyroid Carcinoma in a Colombian Cohort.

INTRODUCTION: In Colombia, thyroid cancer ranks among the highest incidences, yet our population lacks studies on its molecular profile. This study aims to characterize clinical, histopathologic and molecular data in a Colombian cohort with papillary thyroid carcinoma (PTC). METHODS: A retrospective review of clinical history, clinicopathologic characteristics, treatment and 5-10-year follow-up for all patients was done. DNA and RNA were extracted from formalin-fixed paraffin-embedded (FFPE) tissue using the Quick-DNA & RNA FFPE Min iPrep kit (Zymo Research). Next-generation sequencing (NGS) analysis was performed with SOPHiA Solid Tumor Solutions kit (SOPHiA GENETICS). Tumor mutation genomic analysis used SOPHiA DDM™ platform, with descriptive analysis reporting frequencies, means and associations via chi-square analysis. RESULTS: Among 231 sequenced patients, mean age at diagnosis was 46 (± 12.35) years, with higher frequency in women (81.82%). Two cases were reclassified as non-invasive follicular thyroid neoplasm (NIFT-P); an NRAS mutation was found in one of them. Predominant histologic subtype was classic PTC (57.64%) followed by tall cell (28.82%). Of the 229 sequenced carcinomas, mutations were identified in 186 cases, including BRAF, IDH1, RAS and PIK3CA. Notable copy number variations (CNVs) were PDGFRA, CDK4 and KIT, with RET being the most frequent gene fusion, including CCDC6-RET in two classic subtype cases. CONCLUSION: This is the first study in Colombia (TIROSEC) to our knowledge that integrates molecular and histopathologic profiles enriching our local comprehension and knowledge of PTC. The identification of target mutations such as BRAF, RET and NTRK fusions holds the potential to guide targeted therapies for tumor recurrence and predict aggressive behavior.

Prevalence of SARS-CoV-2 infection and SARS-CoV-2-specific antibody detection among healthcare workers and hospital staff of a university hospital in Colombia.

Objective: The aim of this study was to determine current and previous SARS-COV-2 infection, and describe risk factors associated with seropositivity, among HCWs and hospital staff between June and October of 2020. Methodology: Data from the day of enrollment for a prospective cohort study were analyzed to determine point prevalence and seroprevalence of SARS-CoV-2 infection in HCWs and hospital staff of a university hospital in Colombia. Respiratory samples were collected to perform RT-PCR tests, along with blood samples to measure SARS-CoV-2 IgM and IgG antibodies. Data on nosocomial and community risk factors for infection were also collected and analyzed. Findings: 420 HCWs and hospital staff members were included. The seroprevalence at baseline was 23.2%, of which 10.7% had only IgM antibodies, 0.7% had IgG, and 11.7% had IgM and IgG. The prevalence of acute SARS-CoV-2 infection was 1.9%. Being a nurse assistant was significantly associated with seropositivity when compared with all other job duties (PR 2.39, 95% CI 1.27-3.65, p = 0.01). Conclusions: Overall SARS-CoV-2 prevalence was 1.9% and seroprevalence was 23.15%. Nurse assistants, medical doctors or students, and laboratory workers had a higher possibility of being SARS-CoV-2 seropositive.

Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16INK4a status.

BACKGROUND: Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16INK4a in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru. METHODS: HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16INK4a immunohistochemistry. RESULTS: HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16INK4a positivity were observed among HPV positive OPC/OCC cases compared to LC cases. CONCLUSIONS: Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.

Carcinoma of the rete testis: A rare testicular tumor.

Carcinoma of the rete testis is a rare malignant tumor which frequently occurs in middle-aged to older patients and has an aggressive biological behavior. We present the case of a 57-year-old man who presented with an ill-defined mass in the right testicle. The patient underwent a radical orchidectomy. Microscopic evaluation showed a neoplasm displaying a complex papillary-cystic architecture, infiltrating the testicular parenchyma. An in situ proliferation of neoplastic cells, with nuclear stratification and scanty cytoplasm was seen at the periphery, within the channels of the rete testis. The tumor infiltrated the tunica albuginea focally without disrupting it completely. Immunohistochemistry was positive for AE1/AE3, CK7, CK34ßE12, D2-40, and PAX8. Imaging studies presented no evidence of metastatic disease. These findings are those of a primary rete testis carcinoma. The transition between benign and neoplastic rete testis epithelium served as a helpful diagnostic clue. Metastatic carcinomas from other sites were considered in the differential diagnosis.

Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia. METHODS: Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses. RESULTS: Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality. CONCLUSION: Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.

Epithelioid hemangioendothelioma of the parotid gland: a case report in an unusual location with a review of the literature / Hemangioendotelioma epitelioide de la glándula parótida: reporte de un caso de una localización inusual y revisión de la literatura

Epithelioid hemangioendothelioma (EHE) is a malignant vascular tumor that usually affects the liver, lung, bone and deep soft tissues of the extremities or trunk. To our knowledge, only 3 cases in the parotid gland have been reported to date. We report a case of a 62-year-old woman who presented with a 1-year history of a slow-growing, painless mass over the left mandibular angle. Imaging studies showed a 2cm mass over the left parotid gland with peripheral calcifications. The patient underwent a superficial parotidectomy. Sections displayed neoplastic epithelioid cells with cytoplasmic vacuoles containing erythrocytes, surrounded by a myxohyaline stroma. Immunohistochemistry was positive for CD31, CD34, ERG, and factor VIII, but negative for cytokeratin AE1/AE3, CK7, EMA, SMA, and S100. The findings were those of an EHE involving the parotid gland. This case demonstrates an EHE in a rare location and emphasizes the need to consider this tumor when diagnosing uncommon soft tissue tumors of salivary glands

El hemangioendotelioma epitelioide (HEE) es un tumor vascular maligno, que generalmente afecta el hígado, los pulmones, los huesos y los tejidos blandos profundos de las extremidades o el tronco. Por lo que sabemos, solo 3 casos reportados en la literatura han descrito este tumor en la glándula parótida. Presentamos el caso de una mujer de 62 años que presentó una historia de un año, de una masa indolora, de crecimiento lento sobre el ángulo mandibular izquierdo. Los estudios de imagen mostraron una masa de 2cm sobre la glándula parótida izquierda con calcificaciones periféricas. La paciente se sometió a una parotidectomía superficial. Los cortes mostraron células epitelioides neoplásicas con vacuolas citoplasmáticas que contenían eritrocitos, rodeadas por un estroma mixohialino. Se demostró mediante técnicas de inmunohistoquímica positividad en la celularidad neoplásica para CD31, CD34, ERG y factor VIII, pero negatividad para la citoqueratina AE1/AE3, CK7, EMA, SMA y S100. Estos hallazgos fueron los de un HEE comprometiendo la glándula parótida. Este caso demuestra un HEE en una localización rara y enfatiza la necesidad de considerar este tumor al diagnosticar tumores raros de tejidos blandos de glándulas salivales

Epithelioid hemangioendothelioma of the parotid gland: A case report in an unusual location with a review of the literature.

Epithelioid hemangioendothelioma (EHE) is a malignant vascular tumor that usually affects the liver, lung, bone and deep soft tissues of the extremities or trunk. To our knowledge, only 3 cases in the parotid gland have been reported to date. We report a case of a 62-year-old woman who presented with a 1-year history of a slow-growing, painless mass over the left mandibular angle. Imaging studies showed a 2cm mass over the left parotid gland with peripheral calcifications. The patient underwent a superficial parotidectomy. Sections displayed neoplastic epithelioid cells with cytoplasmic vacuoles containing erythrocytes, surrounded by a myxohyaline stroma. Immunohistochemistry was positive for CD31, CD34, ERG, and factor VIII, but negative for cytokeratin AE1/AE3, CK7, EMA, SMA, and S100. The findings were those of an EHE involving the parotid gland. This case demonstrates an EHE in a rare location and emphasizes the need to consider this tumor when diagnosing uncommon soft tissue tumors of salivary glands.

Esophageal tuberculosis in an HIV-positive patient mimicking a spindle cell tumor / Tuberculosis esofágica en un paciente VIH-positivo simulando un tumor de células fusiformes

Tuberculosis (TB) of the esophagus is an extremely rare condition, even in immunocompromised PATIENTS: We report the case of a 24-year-old man with a past history of HIV and pulmonary tuberculosis who presented with dysphagia and a 2cm submucosal mass in the proximal esophagus. The biopsy was diagnosed as a spindle cell neoplasm in another center. Sections displayed a submucosal lesion formed by spindle and epithelioid cells, surrounded by chronic inflammation. The spindle cells were positive for S100 and CD68, but negative for cytokeratin, desmin, smooth muscle actin, ALK, CD34 and CD117. Ziehl-Neelsen stain was performed and showed many intracellular acid-fast bacilli, confirming the diagnosis of esophageal TB. This case is a reminder that esophageal TB may become manifest as a submucosal lesion and the histiocytic-granulomatous reaction may mimic a spindle cell tumor

La tuberculosis (TB) del esófago es una condición extremadamente rara incluso en pacientes inmunocomprometidos. Presentamos el caso de un varón de 24 años con historia médica de VIH y TB pulmonar, que consultó por disfagia y una masa submucosa de 2cm en el esófago proximal. La biopsia fue derivada de una institución externa como una neoplasia de células fusiformes. Los cortes mostraron una lesión submucosa formada por células fusiformes y epitelioides, rodeadas de inflamación crónica. Las células fusiformes fueron positivas para S100 y CD68, pero negativas para citoqueratina, desmina, actina de músculo liso, ALK, CD34 y CD117. Se realizó la tinción de Ziehl-Neelsen y mostró muchos bacilos intracelulares ácido-alcohol resistente, confirmando el diagnóstico de TB esofágica. Este caso es un recordatorio de que la TB esofágica puede manifestarse como una lesión submucosa y la reacción histiocítica-granulomatosa puede simular un tumor de células fusiformes

Esophageal tuberculosis in an HIV-positive patient mimicking a spindle cell tumor.

Tuberculosis (TB) of the esophagus is an extremely rare condition, even in immunocompromised patients. We report the case of a 24-year-old man with a past history of HIV and pulmonary tuberculosis who presented with dysphagia and a 2cm submucosal mass in the proximal esophagus. The biopsy was diagnosed as a spindle cell neoplasm in another center. Sections displayed a submucosal lesion formed by spindle and epithelioid cells, surrounded by chronic inflammation. The spindle cells were positive for S100 and CD68, but negative for cytokeratin, desmin, smooth muscle actin, ALK, CD34 and CD117. Ziehl-Neelsen stain was performed and showed many intracellular acid-fast bacilli, confirming the diagnosis of esophageal TB. This case is a reminder that esophageal TB may become manifest as a submucosal lesion and the histiocytic-granulomatous reaction may mimic a spindle cell tumor.

Helicobacter pylori culture as a key tool for diagnosis in Colombia.

INTRODUCTION: The presence of H. pylori in the stomach is associated with gastric pathologies. However, its diagnosis through culture methods is challenging because of its complex nutritional requirements and microaerophilic conditions for optimal growth. The preferred method for rapid diagnosis of H. pylori is the Rapid Urease Test (RUT) from human biopsies, which relies on the high activity of the urease enzyme present in H. pylori. However, RUT cannot say much more information about H. pylori. This makes evident the need for bacterial culture to know essential information such as the strain type, the kind of infection present and the bacteria's antibiotic susceptibility. METHODOLOGY: Gastric biopsies from 347 patients were used for H. pylori isolation. We correlated the culture results with the RUT and histological grading used at Hospital Universitario Fundación SantaFe de Bogotá (HU-FSFB), Colombia. The concordance between techniques was determined by the Cohen's Kappa coefficient (K). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were also calculated. RESULTS: The culture standardization was successful, and it could be applied for diagnosis in the clinical practice. H. pylori was positive by culture in 88 (26.34%) patients. The concordance of RUT and culture was strong (K= 0.805), and between histology and culture was moderate (K= 0.763) as well as for the gold standard defined and culture (K= 0.80). CONCLUSIONS: We present evidence that RUT and histological methods will be better interpreted for diagnosis of H. pylori if combined with bacterial isolation in cholesterol enriched culture.

Advantage of Z-stacking for teleconsultation between the USA and Colombia.

INTRODUCTION: There is an emerging need for telecytology in Colombia as the demand for cytopathology has increased. However, due to economic and technological constraints telecytology services are limited. Our aim was to evaluate the diagnostic feasibility of using whole slide imaging with and without Z-stacking for telecytology in Colombia, South America. METHODS: Archival glass slides from 17 fine needle aspiration smears were digitized employing whole slide imaging (WSI) (Nanozoomer 2.0 HT, Hamamatsu) in one Z-plane at 40x, and panoramic digital imaging (Panoptiq system, ViewsIQ) combining low-magnification digital maps with embedded 40x Z-stacks of representative regions of interest. Fourteen Colombian pathologists reviewed both sets of digital images. Diagnostic concordance, time to diagnosis, image quality (scale 1-10), usefulness of Z-stacking, and technical difficulties were recorded. RESULTS: Image quality scored by pathologists was on average 8.3 for WSI and 8.7 for panoramic images with Z-stacks (P = .03). However, diagnostic concordance was not impacted by image quality ranking. In the majority of cases (72.4%) pathologists deemed Z-stacking to be diagnostically helpful. Technical issues related to Z-stack video performance constituted only a minor proportion of technical problems reported. Slow downloads and crashing of files while viewing were mostly experienced with larger WSI files. CONCLUSION: This study demonstrated that international telecytology for diagnostic purposes is feasible. Panoramic images had to be acquired manually, but were of suitable diagnostic quality and generated smaller image files associated with fewer technical errors. Z-stacking proved to be useful in the majority of cases and is thus recommended for telecytology.

Malignant Solitary Fibrous Tumor of the Humerus: A Case Report of an Extremely Rare Primary Bone Tumor.

Solitary fibrous tumor (SFT) is a spindle-shaped cell neoplasm originally described in the pleura, but subsequently found in many anatomic sites. Only few cases of primary SFTs in the bone have been previously described in the literature. We present the case of an 86-year-old man with a 1-week history of pain in his left arm. Imaging studies demonstrated a well-defined osteolytic lesion in the proximal humerus measuring 6.1 cm in diameter. Sections showed a round to spindle-shaped cell neoplasm with prominent mitotic activity (28 mitoses per 10 high-power fields) and areas of necrosis, focally surrounding staghorn-shaped vessels. The tumor cells were positive for CD34, CD99, Bcl-2, and STAT6 and negative for smooth muscle actin, epithelial membrane antigen, and cytokeratin AE1/AE3. These findings were consistent with a malignant SFT involving the left humerus. Although extremely rare, SFT should be considered in the differential diagnosis of primary bone tumors. This is the first case report of a primary SFT in a long bone with malignant histological features.

Evaluation of Helicobacter pylori Infection and Clarithromycin Resistance in Strains From Symptomatic Colombian Children.

The aim of the study was to determine the current prevalence of Helicobacter pylori in symptomatic Colombian children and evaluate the presence of mutations associated with clarithromycin resistance. Biopsies from 133 children were analyzed. The gastric fragment was used for urease test and reused for polymerase chain reaction sequencing of the 23SrDNA gene. Mutations were detected by bioinformatic analysis. Polymerase chain reaction sequencing established that H pylori infection was present in 47% of patients. Bioinformatics analysis of the 62 positive sequences for 23SrDNA revealed that 92% exhibited a genotype susceptible to clarithromycin, whereas the remaining strains (8%) showed mutations associated with clarithromycin resistance. The low rate of resistance to clarithromycin (8%) suggests that conventional treatment methods are an appropriate choice for children. Recycling a biopsy that is normally discarded reduces the risks associated with the procedure. The 23SrDNA gene amplification could be used for a dual purpose: detection of H pylori and determination of susceptibility to clarithromycin.

Esophageal Pyogenic Granuloma: A Case Report and Review of the Literature.

Pyogenic granuloma (PG) is a capillary hemangioma mainly found in the skin and oral mucosa, but rarely described in the esophagus. We report the case of a 66-year-old man who consulted for retrosternal pain. Endoscopic studies showed a 28-mm polypoid mass located at the distal esophageal mucosa. The patient underwent endoscopic resection, and the histopathological examination showed a neoplastic proliferation of small blood vessels growing in a lobular architecture, with edematous stroma and prominent inflammatory infiltrate. Special stains for fungus showed pseudohyphae compatible with Candida spp. Findings were consistent with those of an esophageal PG associated with Candida infection. This case is a reminder that PG can be found in the esophagus, can be associated with other entities such as Candida infection, and is one of the differential diagnoses of neoplastic vascular proliferations that may mimic malignancy. In addition, we reviewed previously reported cases of esophageal PG.

Accuracy and interobserver agreement of retroareolar frozen sections in nipple-sparing mastectomies.

In the last decades, surgical treatment of breast cancer has enormously changed. As a result, nipple-sparing mastectomy (NSM) has evolved as an oncologically safe and cosmetic approach. NSM includes a subareolar frozen section to evaluate malignancy. We determined the accuracy of subareolar frozen section diagnosis, analyzed the discrepancy factor, and estimated the interobserver agreement of frozen section in NSM. A retrospective review of all NSMs at our institution from 2009 to 2015 was performed. Frozen sections were compared to the final diagnoses to analyze the accuracy of subareolar frozen sections. Discordant results were rigorously evaluated to identify discrepancy factors. Some cases were randomly chosen to assess the interobserver agreement (kappa) among pathologists. The agreement results were evaluated with and without knowledge of the tumor morphology. Among 34 NSMs, the frozen section false-negative and false-positive rate was 5.9% and 8.8%, respectively. The sensitivity and specificity was 77.8% and 88.0%, respectively. Sampling errors and diathermy artifacts explained our false-negative diagnoses. Freezing artifacts and an intraductal papilloma explained our false-positive diagnoses. The interobserver agreement between breast and general pathologists was 0.87 (p<0.0001) and 0.31 (p=0.0001), respectively. The interobserver agreement increased to 0.35 (p<0.0001) in general pathologists with knowledge of the tumor morphology. Subareolar frozen section showed to be a specific test with moderate sensitivity. Papillary lesions can mimic atypical cells and influence the frozen section interpretation. Frozen section in NSM had a better performance in breast pathologists (almost perfect) versus general pathologists (fair). Interobserver agreement may improve with knowledge of tumor morphology.

Cytologic findings of mammary analogue secretory carcinoma arising in the thyroid.

Mammary analogue secretory carcinoma (MASC) of the salivary gland, first described by Skálová et al in 2010, is a tumor that morphologically and genetically resembles breast secretory carcinoma harboring ETV6-NTRK3 fusion gene. To date, only seven cases of primary thyroid MASC have been described. The overall findings are similar to those seen in the salivary gland counterpart including the ETV6-NTRK3 fusion gene. This is the second report describing the cytologic features of MASC at this primary location, which also showed a classical type papillary carcinoma component. Diagn. Cytopathol. 2017;45:552-556. © 2017 Wiley Periodicals, Inc.

Endometriosis mimicking glandular atypia in a cervical cytology.

Endometriosis involving the uterine cervix is a rare condition that can lead to diagnostic errors in the interpretation of Pap smear. We report the case of a 41-year-old patient in whom the initial Pap smear revealed three-dimensional clusters of glandular cells with elongated nuclei, occasional mitosis, and atypia, which was interpreted as atypical glandular cells, not otherwise specified (NOS). The patient was taken to colposcopy and endocervical biopsy. Colposcopy was normal and the biopsy presented glands with elongated nuclei and surrounded by endometrial stroma admixed with normal endocervical glands. Immunohistochemical studies were reactive for CD10 in the stromal cells and vimentin in endometrioid glands. The findings were consistent with cervical endometriosis. Endometriosis in the cervix is an uncommon pathology that mimics malignancy and may be interpreted as atypical or glandular neoplasia in the cytology.