Depth of invasion analysis to predict acral melanoma outcomes.

BACKGROUND: Acral melanoma is a subtype with worse outcomes. The Breslow micrometric measurement is the most critical parameter in planning treatment and predicting outcomes. However, for acral lentiginous melanoma, the value of the Breslow thickness is a matter of debate. Depth of Invasion (DOI) is a well-established measure for staging oral squamous cell carcinoma. OBJECTIVE: This study compared DOI and Breslow thickness for predicting acral melanoma outcomes. METHODS: We performed a retrospective cross-sectional study of 71 acral melanoma lesions subjected to sentinel lymph node biopsy at one Brazilian referral center. RESULTS: Cox model univariate analysis showed that both DOI and Breslow thickness predicted melanoma specific survival (HR 1.12; p = 0.0255 and HR 1.144; p = 0.0006, respectively), although Kaplan Meier curve was only significant for Breslow (χ2 = 5.792; p = 0.0161) and not for DOI (χ2 = 0.2556; p = 0.6132). Sentinel lymph node status and presence or absence of ulceration also predicted specific survival in patients with acral melanoma (χ2 = 6.3514; p = 0.0117 and χ2 = 4.2793; p = 0.0386, respectively). Multivariate analysis, however, demonstrated that Breslow depth was the only independent parameter for predicting acral melanoma specific survival (HR 1.144; p = 0.0006). CONCLUSION: Even though Breslow thickness remains the main predictor for survival in acral melanoma, it is not a perfect parameter. The introduction of DOI in this context opens new perspectives for predicting acral melanoma outcomes.

Oral lesions of systemic lupus erythematosus: A collaborative Latin American study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that may affect the oral mucosa. The variable spectrum of oral lesions observed in SLE can pose challenges in diagnosis, particularly when the lesions occur in isolation. The aim of this study was to describe the oral lesions occurring in patients with SLE from Latin America. METHODS: This collaborative record-based study involving 11 oral and maxillofacial pathology and medicine services across Venezuela, Argentina, Chile, Brazil, and Mexico describes the clinicopathological profile of SLE-related oral lesions. RESULTS: Seventy patients with SLE and oral lesions were included in the study. The majority were females (75.7%; female/male ratio: 3.1:1) and white (62.1%), with a mean age of 38.4 years (range: 11-77 years). The most common site of oral lesions was the hard/soft palate (32.0%). Clinically, oral lesions predominantly presented as ulcers (26.6%), erosions (26.6%), and white lesions (23.4%). Isolated oral lesions occurred in 65.2% of individuals, while cutaneous manifestations occurred in 80.3%. The main clinical diagnostic hypothesis in 71.4% of cases was an immune-mediated disease. Oral biopsies followed by histopathological analysis were performed in 50 cases. CONCLUSION: Oral lesions of SLE exhibit a variety of clinical and histopathological features. A key point in diagnosis is that unusual oral changes without an obvious local cause may indicate a possible systemic condition presenting with oral lesions. A multidisciplinary approach, which includes regular oral examination, is warranted to identify oral lesions and provide treatment.

Expression of ß1- and ß2-adrenergic receptors in oral squamous cell carcinoma and their association with psychological and clinical factors.

BACKGROUND: Psychological stressors have been related to tumor progression through the activation of beta-adrenergic receptors (ß-AR) in several types of cancer. PURPOSE: This study aimed to investigate the expressions of ß1- and ß2-AR and their association with psychological and clinicopathological variables in patients with oral squamous cell carcinoma. METHODS: Tumor samples from 99 patients diagnosed with OSCC were subjected to immunohistochemical reaction to detect the expression of ß1-AR and ß2-AR. Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory and Beck Depression Inventory (BDI), respectively. The Brunel Mood Scale was used for measuring affective mood states. RESULTS: Univariate analyzes revealed that higher expression of ß1-AR was associated with increased alcohol consumption (p = 0.032), higher education (p = 0.042), worse sleep quality (p = 0.044) and increased levels of pain related to the primary tumor (p < 0.001). Higher expression of ß2-AR was related with regional metastasis (p = 0.014), increased levels of pain related to the primary tumor (p = 0.044), anxiety (p < 0.001) and depressive (p = 0.010) symptoms and higher mood scores of angry (p = 0.010) and fatigue (p = 0.010). Multivariate analysis identified that patients with advanced clinical stage had lower ß1-AR expression (OR=0.145, 95% CI=0.025-0.828, p = 0.003). Higher anxiety symptoms and higher mood fatigue are independent factors for increased ß2-AR expression (OR=4256, 95% CI=1439-12606, p = 0.009; OR=3816, 95% CI=1258-11,573, p = 0.018, respectively). CONCLUSION: This study reveal that anxiety, fatigue symptoms, and clinical staging are associated with tumor expression of beta-adrenergic receptors in patients with oral cancer.

Proposal for the applicability of modified Breslow (measured from the basal membrane) as a predictor of survival and sentinel lymph node outcome in patients with cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is a neoplasm with a high mortality rate and risk of metastases to distant organs. The Breslow micrometric measurement is considered the most important factor for evaluating prognosis and management, measured from the granular layer to the deepest portion of the neoplasm. Despite its widespread use, the Breslow thickness measurement has some inaccuracies, such as not considering variations in the thickness of the epidermis in different body locations or when there is ulceration. OBJECTIVE: To evaluate the applicability of a modified Breslow measurement, measured from the basal membrane instead of from the granular layer, in an attempt to predict sentinel lymph node examination outcome and survival of patients with melanoma. METHODS: A retrospective and cross-sectional analysis was carried out based on the evaluation of slides stained with hematoxylin & eosin from 275 cases of melanoma that underwent sentinel lymph node biopsy from 2008 to 2021 at a reference center in Brazil. RESULTS: Analysis of the Cox model to evaluate the impact of the Breslow measurement and the modified Breslow measurement on survival showed that both methods are statistically significant. Logistic regression revealed a significant association between both measurements and the presence of metastasis in sentinel lymph nodes. CONCLUSION: Measuring melanoma depth from the basal membrane (modified Breslow measurement) is capable of predicting survival time and sentinel lymph node outcome, as well as the conventional Breslow measurement.

Primary manifestation of HIV-related Burkitt lymphoma in the oral and maxillofacial regions.

BACKGROUND: Burkitt lymphoma (BL) is a subtype of non-Hodgkin lymphoma. It is strongly associated with HIV infection and has a highly aggressive clinical course. The involvement of the maxillofacial region in BL has rarely been reported. CASE DESCRIPTION: A 36-year-old woman with HIV-positive status had painless bilateral swelling of the oral mucosa and middle and lower thirds of the face. Microscopic analysis of the oral lesion revealed an atypical lymphoid infiltrate with a starry sky pattern. The lymphoid cells expressed cluster of differentiation 20, cluster of differentiation 10, B-cell lymphoma 6, and c-Myc; the Ki-67 proliferative index was high. The tumor cells were positive for Epstein-Barr virus. These results led to the diagnosis of HIV-related BL. PRACTICAL IMPLICATIONS: BL and other immunodeficiency-related lymphoproliferative malignancies may affect the oral and maxillofacial regions and should be included in the differential diagnosis of rapidly expanding swelling in young patients.

Macroscopic tumor dimension, sentinel lymph node outcome, and survival analysis among cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is characterized by a high risk of metastasis to distant organs and a substantial mortality rate. For planning treatment and assessing outcomes, the Breslow micrometric measurement is critical. The tumor macroscopic dimension is not considered a prognostic parameter in cutaneous melanoma, although there are studies showing that tumor size is an independent prognostic factor for melanoma-specific survival. Therefore, this study aimed to evaluate the macroscopic dimension of melanoma and other known prognostic factors (i.e., Breslow index, mitoses, regression, and ulceration) as predictors of sentinel lymph node outcome and survival outcome. METHODS: We performed a retrospective cross-sectional study of 227 melanoma lesions subjected to sentinel lymph node biopsy at two Brazilian referral centers. RESULTS: On univariate analysis, there was a statistically significant correlation between the largest macroscopic tumor dimension and the sentinel lymph node result (P = 0.001); however, on multivariate analysis considering all evaluated parameters, there was no significant difference between the sentinel lymph node result and the tumor macroscopic dimension (P = 0.2689). Regarding melanoma-specific survival, the macroscopic dimension showed no significant correlation (P = 0.4632) in contrast to Breslow's dimension (P < 0.0001). CONCLUSION: The Breslow thickness was the only significant factor related to both the sentinel lymph node outcome and melanoma specific survival among the evaluated variables.

Bilateral intra-lymph node Warthin's tumor as a potential diagnostic pitfall mimicking metastatic carcinoma.

Warthin's tumor (WT) is a benign and frequent salivary gland tumor primarily affecting the parotid gland. In some cases, this tumor can involve the extra parotid region and affect cervical lymph nodes. Fine-needle aspiration can be the first step in the diagnostic approach to lymphadenopathy; however, specimens from intra-nodal WT can present a potential pitfall, leading to a misdiagnosis of metastasis. Here, we report an unusual case of a patient with bilateral WT in parotid lymph nodes misdiagnosed as metastases. In addition, we highlight the cytopathological aspects of WT to alert cytopathologists about this challenging diagnosis.

Proposal for the applicability of modified Breslow (measured from the basal membrane) as a predictor of survival and sentinel lymph node outcome in patients with cutaneous melanoma

Abstract Background Cutaneous melanoma is a neoplasm with a high mortality rate and risk of metastases to distant organs. The Breslow micrometric measurement is considered the most important factor for evaluating prognosis and management, measured from the granular layer to the deepest portion of the neoplasm. Despite its widespread use, the Breslow thickness measurement has some inaccuracies, such as not considering variations in the thickness of the epidermis in different body locations or when there is ulceration. Objective To evaluate the applicability of a modified Breslow measurement, measured from the basal membrane instead of from the granular layer, in an attempt to predict sentinel lymph node examination outcome and survival of patients with melanoma. Methods A retrospective and cross-sectional analysis was carried out based on the evaluation of slides stained with hematoxylin & eosin from 275 cases of melanoma that underwent sentinel lymph node biopsy from 2008 to 2021 at a reference center in Brazil. Results Analysis of the Cox model to evaluate the impact of the Breslow measurement and the modified Breslow measurement on survival showed that both methods are statistically significant. Logistic regression revealed a significant association between both measurements and the presence of metastasis in sentinel lymph nodes. Conclusion Measuring melanoma depth from the basal membrane (modified Breslow measurement) is capable of predicting survival time and sentinel lymph node outcome, as well as the conventional Breslow measurement.

Digital analyses of nuclear features can help discriminate among non-invasive follicular thyroid neoplasm with papillary-like nuclear features, papillary thyroid carcinoma follicular subtype, and follicular carcinoma in cytological specimens.

BACKGROUND: As it stands, the diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is primarily based on histological analysis. We hypothesised that computerised analysis of nuclear images of cytological specimens could be used to differentiate NIFTP from papillary thyroid carcinoma follicular subtype (PTCFS) and follicular carcinoma (FC), influencing patient management. METHODS: We employed a retrospective analytical observational study based on nuclear morphometric variables of cytological material from thyroid nodules classified as PTCFS, NIFTP, or FC. Five cases of each entity were analysed. Cytological slides were photographed, and 1170 cells for each entity were analysed digitally. The captured images were evaluated (blindly) using the ImageJ software package. The morphometric evaluation included area, perimeter, width, height, and circularity. Numerical variables were expressed as mean, median, minimum, and maximum (min; max) values. Kruskal-Wallis and Dunn's tests were used with a 5% significance level. RESULTS: Regarding nuclear analysis, all variables differed among the three groups (p < 0.001). Given the interdependence among the variables, these data indicated that nuclear size was greatest in the NIFTP group, followed by FC and PTCFS. DISCUSSION/CONCLUSION: Our analysis of the digital images, with a focus on nuclear parameters, found significantly difference among cytological specimens from cases of NIFTP, PTCFS and FC. Thus, this tool has the potential to provide additional information that may help in the diagnosis of NIFTP, even during the preoperative period. Additional studies are needed to create protocols, evaluate the applicability of nuclear morphological and morphometric parameters-focusing on digital pathology-and create algorithms and tools to assist cytopathologists with their diagnostic routines.

Underestimated Cervical Cancer among Women over 65 Years Old: Is It Time to Revise the Screening Target Age Group?

OBJECTIVE: To compare cytological and histological results from women > 64 years old who followed the Brazilian national cervical cancer screening guidelines with those who did not. METHODS: The present observational retrospective study analyzed 207 abnormal cervical smear results from women > 64 years old in a mid-sized city in Brazil over 14 years. All results were reported according to the Bethesda System. The women were divided into those who followed the screening guidelines and those who did not. RESULTS: Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion cytology results were found in 128 (62.2%) cases. Of these, 112 (87.5%) had repeated cytology with positive results. The other 79 (38.1%) with abnormal results should have been referred to colposcopy and biopsy. Out of 41 (51.9%) biopsied women, 23 (29.1%) had a confirmed diagnosis of neoplasia or precursor lesion. In contrast, among the 78 (37.7%) biopsied patients, 40 (51.3%) followed the guideline recommendations, with 9 (22.5%) positive biopsies. Of the 38 (48.7%) women who did not follow the guidelines, there were 24 (63.1%) positive results. Women who did not follow the guidelines demonstrated higher chances of cancer and precursor lesions (odds ratio [OR]: 5.904; 95% confidence interval [CI]: 2.188-15.932; p = 0.0002). CONCLUSION: Women > 64 years old who did not follow the national screening protocol showed significant differences in the frequency of abnormal results and severity of diagnosis compared with those who followed the protocol.

OBJETIVO: Comparar os resultados citológicos e histológicos de mulheres > 64 anos que seguiram as diretrizes nacionais brasileiras de rastreamento do câncer do colo do útero com aquelas que não as seguiram. MéTODO: O presente estudo observacional retrospectivo analisou 207 resultados anormais de esfregaço cervical de mulheres > 64 anos de idade em uma cidade de médio porte no Brasil durante 14 anos. Todos os resultados foram relatados de acordo com o Sistema Bethesda. As mulheres foram divididas entre as que seguiram as diretrizes de rastreamento e as que não o fizeram. RESULTADOS: Resultados citológicos com células escamosas atípicas de significado indeterminado e lesão intraepitelial escamosa de baixo grau foram encontrados em 128 (62,2%) casos. Destes, 112 (87,5%) repetiram a citologia com resultados positivos. Os outros 79 (38,1%) com resultados anormais deveriam ter sido encaminhados para colposcopia e biópsia. Das 41 (51,9%) mulheres biopsiadas, 23 (29,1%) tiveram diagnóstico confirmado de neoplasia ou lesão precursora. Em contrapartida, entre as 78 (37,7%) pacientes biopsiadas, 40 (51,3%) seguiram as recomendações da diretriz, com 9 (22,5%) biópsias positivas. Entre as 38 (48,7%) mulheres que não seguiram as orientações, houve 24 (63,1%) resultados positivos. As mulheres que não seguiram as diretrizes demonstraram maiores chances de câncer e lesões precursoras (odds ratio [OR]: 5,904; intervalo de confiança [IC] de 95%: 2,188­15,932; p = 0,0002). CONCLUSãO: Mulheres > 64 anos que não seguiram a diretriz nacional de rastreamento apresentaram diferenças significativas na frequência de resultados anormais e gravidade do diagnóstico em comparação com aquelas que seguiram a diretriz.

Underestimated Cervical Cancer among Women over 65 Years Old: Is It Time to Revise the Screening Target Age Group? / Câncer cervical subestimado entre mulheres com mais de 65 anos: É hora de rever a faixa etária alvo do rastreamento?

Abstract Objective To compare cytological and histological results from women > 64 years old who followed the Brazilian national cervical cancer screening guidelines with those who did not. Methods The present observational retrospective study analyzed 207 abnormal cervical smear results from women > 64 years old in a mid-sized city in Brazil over 14 years. All results were reported according to the Bethesda System. The women were divided into those who followed the screening guidelines and those who did not. Results Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion cytology results were found in 128 (62.2%) cases. Of these, 112 (87.5%) had repeated cytology with positive results. The other 79 (38.1%) with abnormal results should have been referred to colposcopy and biopsy. Out of 41 (51.9%) biopsied women, 23 (29.1%) had a confirmed diagnosis of neoplasia or precursor lesion. In contrast, among the 78 (37.7%) biopsied patients, 40 (51.3%) followed the guideline recommendations, with 9 (22.5%) positive biopsies. Of the 38 (48.7%) women who did not follow the guidelines, there were 24 (63.1%) positive results. Women who did not follow the guidelines demonstrated higher chances of cancer and precursor lesions (odds ratio [OR]: 5.904; 95% confidence interval [CI]: 2.188-15.932; p = 0.0002). Conclusion Women > 64 years old who did not follow the national screening protocol showed significant differences in the frequency of abnormal results and severity of diagnosis compared with those who followed the protocol.

Resumo Objetivo Comparar os resultados citológicos e histológicos de mulheres > 64 anos que seguiram as diretrizes nacionais brasileiras de rastreamento do câncer do colo do útero com aquelas que não as seguiram. Método O presente estudo observacional retrospectivo analisou 207 resultados anormais de esfregaço cervical de mulheres > 64 anos de idade em uma cidade de médio porte no Brasil durante 14 anos. Todos os resultados foram relatados de acordo com o Sistema Bethesda. As mulheres foram divididas entre as que seguiram as diretrizes de rastreamento e as que não o fizeram. Resultados Resultados citológicos com células escamosas atípicas de significado indeterminado e lesão intraepitelial escamosa de baixo grau foram encontrados em 128 (62,2%) casos. Destes, 112 (87,5%) repetiram a citologia com resultados positivos. Os outros 79 (38,1%) com resultados anormais deveriam ter sido encaminhados para colposcopia e biópsia. Das 41 (51,9%) mulheres biopsiadas, 23 (29,1%) tiveram diagnóstico confirmado de neoplasia ou lesão precursora. Em contrapartida, entre as 78 (37,7%) pacientes biopsiadas, 40 (51,3%) seguiram as recomendações da diretriz, com 9 (22,5%) biópsias positivas. Entre as 38 (48,7%) mulheres que não seguiram as orientações, houve 24 (63,1%) resultados positivos. As mulheres que não seguiram as diretrizes demonstraram maiores chances de câncer e lesões precursoras (odds ratio [OR]: 5,904; intervalo de confiança [IC] de 95%: 2,188-15,932; p = 0,0002). Conclusão Mulheres > 64 anos que não seguiram a diretriz nacional de rastreamento apresentaram diferenças significativas na frequência de resultados anormais e gravidade do diagnóstico em comparação com aquelas que seguiram a diretriz.

The impact of transformation zone representation on the frequency of abnormal cervical cytological results.

OBJECTIVE: To compare the frequency of abnormal cervical cytological results with and without representation of the transformation zone (TZ) in a medium-sized city in Brazil according to the Bethesda categorization. METHODS: We performed an analytical observational study evaluating cytological results over 15 years from conventional smears collected within the Public Brazilian Health System in Araçatuba, Brazil. Tests were stratified by age and cytological result according to Brazilian guidelines and the Bethesda System. RESULTS: There were 261,881 examinations, 159,251 with and 102,630 without TZ representation. The global frequency of abnormal results was higher in smears with TZ representation (crude odds ratio [OR] 4.03; 95% confidence interval [CI] [3.71-4.38]). Considering only women between 25 and 64 years (the target of the national guidelines), there were higher results for high-grade squamous intraepithelial lesions (OR 11.54; 95% CI 6.74-19.78), low-grade squamous intraepithelial lesions (OR 2.82; 95% CI 2.17-3.67) atypical squamous cell in which high-grade intraepithelial lesion cannot be excluded (OR 6.90; 95% CI 4.91-9.66) and atypical squamous cell of undetermined significance (OR 3.53; 95% CI 3.11-4.01) among cases with TZ representation. CONCLUSION: Samples with TZ representation were associated with higher rates of abnormal results. Health professionals should be regularly trained to understand the weakness of cytological examinations when the TZ is not represented, especially in developing countries.

Cervical cytology results among pregnant and non-pregnant women in Brazil.

OBJECTIVE: To compare the prevalence of abnormal cervical smear results among pregnant and non-pregnant women with and without representation of the transformation zone (TZ) in a mid-sized city in Brazil. STUDY DESIGN: This observational analytical and retrospective study analyzed cervical smear results from pregnant and non-pregnant women in a mid-sized city in Brazil. Private data were collected at private clinics over seven years and from public services over 16 years. All results were reported according to Bethesda System. Pregnant women were separated from non-pregnant women, and women were stratified into two age groups (25-29 years and 30-34 years) in general analyses. For TZ representation and cytologic-histologic correlation, there was no age stratification. RESULTS: Among public services cervical smears, the frequency of atypical squamous cells of undetermined significance (ASC-US) was higher for pregnant women in the entire group (odds ratio [OR] 1.91; confidence interval [CI] 1.07-3.39) and among women from 30 to 40 years old (OR 2.79; CI 1.38-5.66). The same occurred for low-grade squamous intraepithelial lesion (LSIL) in the total group (OR 3.50; CI 1.44-8.53) and among women 30 to 40 years old (OR 4.57; CI 1.45-14.42). The frequency of ASC-US was higher in pregnant women with TZ representation exams than those without (OR 4.62; CI 2.17-9.84). The same occurred for those with atypical squamous cells, which cannot exclude high-grade squamous intraepithelial lesion (OR 9.81; CI 1.63-59.15) and LSIL (OR 10.47; CI 3.39-32.36). Among pregnant women with abnormal cervical smear results, 85.74% were followed up through cytology, and an average of 26.12% of patients underwent biopsy, of which almost all were positive for dysplasia. CONCLUSION: Pregnant and non-pregnant women did not differ in cervical smears with actual precursor lesions. Nevertheless, considering the opportunistic nature of Brazilian cervical cancer screening, prenatal visits present an opportunity to perform cervical smears in pregnant women. TZ representation correlated with higher rates of abnormal cervical smears, reinforcing the clinical importance of endocervical/metaplastic cell representation, including among pregnant women.

Score system for cytological evaluation of fine-needle aspiration specimens to predict the diagnosis of papillary thyroid carcinomas.

INTRODUCTION: According to the World Health Organization's classification of endocrine tumors, papillary thyroid carcinoma (PTC) accounts for almost 90 % of malignant thyroid neoplasms. This study aimed to create a point system based on cytomorphological criteria for evaluating FNA products from thyroid nodules to predict the risk of papillary thyroid carcinomas. METHODS: This was an analytical observational study based on a retrospective analysis of cytological reports and surgical specimens from January 1, 2016, to December 31, 2021. Cytological slides were analyzed using the following ten variables: Nuclear Grooves; Intranuclear Pseudoinclusion; Cellularity; Colloid (Quantity); Clarified Chromatin; Overlapping nuclei; Irregular Nuclear Membrane; Multinucleated Giant Cells; Psamoma bodies; and Papillae. We categorized these variables quantitatively from zero to three points as follows: zero (absent), one (mild), two (moderate), and three (intense). RESULTS: Cytologies of 254 (4.9 %) cases were analyzed. The cut-off point was defined in this study as 6 ± 1 points. For the prediction of cases in benign, values < 5 points, malignant, values > 7 points and indeterminate, 5-7 points. Among the benign, there were 64 (69.5 %) cases <5 points, 17 (18.4 %) from 5 to 7 points and 11 (11.9 %) >7 points. Among the malignant ones, there were 12 (8.6 %) cases <5 points, 19 (13.6 %) from 5 to 7 points and 108 (77.6) >7 points. CONCLUSION: In this context, through the quantitative analysis of the ten suggested cytological variables, scored from 0 to 3, a final score > 7 is suspicious for malignancy, while a score < 5 is related to benign lesions.