An executive summary of the Philippine Interim Clinical Practice Guidelines for the Diagnosis and Management of Well Differentiated Thyroid Cancer 2021

Objectives@#Thyroid cancer is the most common endocrine cancer in the Philippines affecting primarily women in the reproductive age group. Considering the burden of thyroid cancer in the country, the Department of Health (DOH) called for the development of a national clinical practice guideline that would address patient needs, and aid physicians in clinical decision-making while considering therapeutic cost and availability in the local setting. The 2021 guidelines are aimed at providing optimal care to Filipino patients by assisting clinicians in the evaluation of thyroid nodules and management of well differentiated thyroid cancer.@*Methods@#A steering committee convened to formulate clinical questions pertaining to the screening and evaluation of thyroid nodules, surgical and post operative management of thyroid cancer, and palliative care for unresectable disease. A technical working group reviewed existing clinical guidelines, retrieved through a systematic literature search, synthesized clinical evidence, and drafted recommendations based on the ADAPTE process of clinical practice guideline development. The consensus panel reviewed evidence summaries and voted on recommendations for the final statements of the clinical practice guidelines.@*Results@#The guidelines consist of clinical questions and recommendations grouped into six key areas of management of well differentiated thyroid cancer: screening, diagnosis, surgical treatment, post operative management, surveillance, and palliative care.@*Conclusion@#The 2021 guidelines for well differentiated cancer could direct physicians in clinical decision making, and create better outcomes for Filipino patients afflicted with the disease. However, patient management should still be governed by sound clinical judgement and open physician-patient communication.

Carcinoma testicular de células germinales no seminomatoso estadio I, supervivencia global en pacientes posterior a tratamiento primario / Testicular non-seminomatous germ cell carcinoma stage I, overall survival in patients following primary treatment

Objetivo: Caracterizar la supervivencia global (SG) y la supervivencia libre de recurrencia (SLR) de pacientes con carcinoma testicular de células germinales no seminomatoso (NSGCT) estadio I derivados a diferentes opciones de adyuvancia. Método: Búsqueda de pacientes con NSGCT estadio I llevados a orquiectomía radical del 2010-2022. La descripción se hizo con medidas de tendencia central. Resultados: En el modelo de regresión no hubo diferencias. Conclusiones: No se encontraron diferencias en SG o SLR. Se requieren estudios prospectivos para corroborar hallazgos

Objective: To characterize overall survival (OS) and recurrence-free survival (RFS) in patients with stage I testicular non-seminomatous germ cell carcinoma (NSGCT) referred to different adjuvant treatment options. Method: Patient search included individuals with stage I NSGCT who underwent radical orchiectomy from 2010 to 2022. The statistical description was conducted using measures of central tendency. Results: In the regression model, no differences were observed. Conclusions: No differences were found in OS or RFS. Prospective studies are needed to confirm these findings

Extensive carcinoma cuniculatum of the maxilla: A rare variant of oral carcinoma

Carcinoma cuniculatum (CC), is a rare well-differentiated, low-grade variant of squamous cell carcinoma. However, diagnosis of oral CC has remained very difficult, because many pathologists and clinicians remain un acquainted with oral CC, because there are very few reported cases of this disease in the oral cavity. To our knowledge, no more than 60 head and neck cases have been reported since Flieger and Owinski first described a case involving the mandible in 1977, because there are very few published cases of this disease in the oral cavity, the aim of this report is to provide a detailed clinical and histopathologic description of carcinoma cuniculatum of the maxila, provide a brief review of the literature, and highlight the difficulties in arriving at the correct diagnosis.

Manejo multidisciplinario en un caso refractario de obstrucción intestinal maligna / Multidisciplinary management in a refractory case of malignant intestinal obstruction

Se denomina obstrucción intestinal maligna (OIM) a aquella alteración del tránsito intestinal por obstrucción mecánica o funcional, que genera alteración de la motilidad y acumulación de secreciones, causada por tumores malignos. Es una urgencia oncológica y paliativa de difícil manejo, esta entidad representa un reto para el equipo de salud, debido al gran impacto sobre la calidad de vida del paciente y su familia. Se presenta el caso de una paciente femenina de 73 años, con características clínicas de obstrucción intestinal maligna, evaluada inicialmente por oncología médica quienes diagnostican carcinoma seroso de alto grado de ovario y carcinomatosis peritoneal, se solicita manejo conjunto con un equipo multidisciplinario para tratar la obstrucción intestinal maligna refractaria a medicación convencional, donde se opta por sedación superficial intermitente; así mismo se aborda preferencias y cuidados de final de vida en domicilio con la paciente y su familia. Este caso es un ejemplo del manejo integral de casos refractarios a la obstrucción intestinal maligna, donde se logra aliviar el sufrimiento del paciente y su familia, cuando la cirugía no es una opción

Malignant intestinal obstruction (MIO) is defined as that alteration of intestinal transit due to mechanical or functional obstruction, which generates impaired motility and accumulation of secretions, caused by malignant tumors. It is an oncological and palliative emergency that is difficult to manage, this entity represents a challenge for the health team, due to the great impact on the quality of life of the patient and his family. The case of a 73-year-old female patient is presented, with clinical characteristics of malignant intestinal obstruction, initially evaluated by medical oncology who diagnosed high-grade serous ovarian carcinoma and peritoneal carcinomatosis, joint management with a multidisciplinary team is requested to treat malignant intestinal obstruction refractory to conventional medication, where intermittent superficial sedation is chosen; Likewise, preferences and end-of-life care at home are addressed with the patient and her family This case is an example of the comprehensive management of cases refractory to malignant intestinal obstruction, where it is possible to alleviate the suffering of the patient and her family, when surgery is not an option

Carcinoma suprarrenal: presentación de caso clínico / Adrenal carcinoma: clinical case presentation / Carcinoma adrenal: apresentação de caso clínico

El carcinoma suprarrenal es una enfermedad muy poco frecuente de presentación clínica poco específica, donde los síntomas por la propia neoplasia son los predominantes. El objetivo de esta publicación es presentar un caso clínico jerarquizando los estudios de imagen para el diagnóstico y la planificación de la táctica para la cirugía.

Adrenal carcinoma is a very rare disease with nonspecific clinical presentation, where symptoms from the neoplasia itself are predominant. The aim of this publication is to present an uncommon clinical case, emphasizing the role of imaging studies in diagnosis and surgical strategy planning.

O carcinoma adrenal é uma doença muito rara, com apresentação clínica inespecífica onde predominam os sintomas decorrentes da própria neoplasia. O objetivo desta publicação é apresentar um caso clínico infrequente priorizando exames de imagem para diagnóstico e planejamento de táticas cirúrgicas.

Carcinoma neuroendocrino de la piel: Carcinoma de células de Merkel. Revisión de la Literatura, a propósito de un caso / Neuroendocrine skin carcinoma: Merkel cell carcinoma. Review of literature, about a case

El carcinoma de células de Merkel, también llamado carcinoma neuroendocrino de la piel, es un tipo de cáncer de piel muy poco frecuente que generalmente aparece como un nódulo de color carne o rojo azulado, más frecuentemente en región facial, cabeza y cuello. El carcinoma de células de Merkel se desarrolla principalmente en personas mayores ya que la exposición al sol a largo plazo o un sistema inmunitario débil pueden aumentar el riesgo de desarrollarlo. Las células de Merkel se encuentran en la base de la capa más externa de la piel (epidermis) y están conectadas a las terminaciones nerviosas que son responsables del sentido del tacto. Tiende a crecer rápido y diseminarse a otras partes del cuerpo. Por tanto, las opciones de tratamiento para el carcinoma de células de Merkel dependen de si el cáncer se ha diseminado más allá de la piel

Merkel cell carcinoma, also called neuroendocrine skin of the skin, is a very rare type of skin cancer that generally appears as a bluish meat or red color nodule, more frequently in the facial, head and neck region. Merkel cell carcinoma develops mainly in older people since long -term exposure or a weak immune system can increase the risk of developing it. Merkel cells are at the base of the outermost layer of the skin (epidermis) and are connected to nerve endings that are responsible for the sense of touch. It tends to grow quickly and spread to other parts of the body. Therefore, the treatment options for Merkel cell carcinoma depend on whether cancer has spread beyond the skin

Relevancia y prevalencia de los parámetros histopatológicos y subtipos moleculares del cáncer de mama en mujeres del área costera de Ecuador atendidas en una institución de Salud Pública / Prevalence and significance of breast cancer pathologycal subtypes in Ecuador

BACKGROUND: The success of breast cancer (BC) treatment depends largely on the clinical-histological characteristics of the patient. Immunohistochemical (IHC) Breast Cancer Subtypes are crucial for therapeutic purposes. AIM: To determine the relevance and prevalence of the histopathological parameters and molecular subtypes of BC among women attending public health services. MATERIAL AND METHODS: A retrospective cross-sectional study was carried out in 199 female patients with histopathological diagnosis of breast cancer, treated at a Guayaquil city hospital in Ecuador, from January 2014 to December 2017. RESULTS: Luminal A carcinoma was the most prevalent tumor in the studied women (54%). Thirty seven percent of patients did not have nodal involvement, 40% had one to three lymph nodes involved and 2% had 10 or more nodes involved. Most patients had a tumor size > 2 and ≤ 5 cm (72%) and moderately differentiated specifications (57%). CONCLUSIONS: The study allowed the characterization of breast cancer according to the prevalence of molecular subtypes and clinical and histological characteristics. These factors determine therapeutic behaviors that optimize the use of the limited resources of the Public Health System.

Arsenic Trioxide: Pharmacological Applications / Trióxido de Arsénico: Aplicaciones farmacológicas

Background: Arsenic trioxide is a chemical compound that has been used as a treatment for various diseases. Despite being potentially toxic, this compound has been used as a therapy to treat Acute Myeloid Leukemia and is being investigated as a possible treatment for different types of cancer. Objectives: The present review aims to describe the use and studies reported in the literature of Arsenic Trioxide as a possible therapeutic agent for Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndrome, Hepatocellular Carcinoma, Lung Cancer, Neuroblastoma, Breast Cancer, Aplastic Hepatitis C, and HIV-1. Methods: A systematic review was conducted using databases (Elsevier, Google Scholar, PubMed) to compile documents published before December 2023. Results:Multiple pharmacological applications of arsenic trioxide have been reported to treat acute and chronic myeloid leukemia. Arsenic trioxide has been shown to inhibit angiogenesis, which helps treat multiple myeloma. Several studies have shown and suggested the effectiveness of arsenic trioxide as a treatment of hepatocellular carcinoma, lung cancer, neuroblastoma, prostate cancer, breast cancer, aplastic anemia, hepatitis C, and HIV-1. Conclusion: Despite potentially toxic effects, Arsenic compounds are therapeutic agents for multiple diseases, from syphilis to cancer. In recent years, more efficient ways have been investigated to deliver and find the specific dose to treat the disease, causing the fewest possible adverse effects.

Antecedentes: El trióxido de arsénico es un compuesto químico que se ha utilizado como tratamiento de diversas enfermedades. A pesar de ser potencialmente tóxico, este compuesto se ha utilizado como terapia para tratar la leucemia mieloide aguda y se está investigando como posible tratamiento para diferentes tipos de cáncer. Objetivos: La presente revisión pretende describir el uso del trióxido de arsénico como posible agente terapéutico para la leucemia mieloide aguda, la leucemia promielocítica aguda, la leucemia mieloide crónica, el mieloma múltiple, el síndrome mielodisplásico, el carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de mama, la hepatitis C aplásica y el VIH-1. Métodos: Se realizó una revisión sistemática utilizando bases de datos (Elsevier, Google Scholar, PubMed) para recopilar documentos publicados antes de diciembre de 2023. Resultados: Se ha informado de múltiples aplicaciones farmacológicas del trióxido de arsénico para tratar la leucemia mieloide aguda y la leucemia mieloide crónica. Se ha demostrado que el trióxido de arsénico inhibe la angiogénesis, lo que resulta útil para el tratamiento del mieloma múltiple. Varios estudios han demostrado y sugerido la eficacia del trióxido de arsénico como tratamiento del carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de próstata, el cáncer de mama, la anemia aplásica, la hepatitis C y el VIH-1. Conclusión: A pesar de tener un efecto potencialmente tóxico, los compuestos de arsénico destacan como agentes terapéuticos para múltiples enfermedades, desde la sífilis hasta el cáncer. En los últimos años, se han investigado formas más eficientes de administrar y encontrar la dosis específica para poder tratar la enfermedad, causando los menores efectos adversos posibles.

A cervical cancer tissue-derived decellularized extracellular matrix scaffold for cervical cancer tissue reconstruction in vitro / 南方医科大学学报

OBJECTIVE@#The prepare decellularized extracellular matrix (ECM) scaffold materials derived from human cervical carcinoma tissues for 3D culture of cervical carcinoma cells.@*METHODS@#Fresh human cervical carcinoma tissues were treated with sodium lauryl ether sulfate (SLES) solution to prepare decellularized ECM scaffolds. The scaffolds were examined for ECM microstructure and residual contents of key ECM components (collagen, glycosaminoglycan, and elastin) and genetic materials by pathological staining and biochemical content analysis. In vitro 3D culture models were established by injecting cultured cervical cancer cells into the prepared ECM scaffolds. The cells in the recellularized scaffolds were compared with those in a conventional 2D culture system for cell behaviors including migration, proliferation and epithelial-mesenchymal transition (EMT) wsing HE staining, immunohistochemical staining and molecular biological technology analysis. Resistance to 5-fluorouracil (5-Fu) of the cells in the two culture systems was tested by analyzing the cell apoptosis rates via flow cytometry.@*RESULTS@#SLES treatment effectively removed cells and genetic materials from human cervical carcinoma tissues but well preserved the microenvironment structure and biological activity of ECM. Compared with the 2D culture system, the 3D culture models significantly promoted proliferation, migration, EMT and 5-Fu resistance of human cervical cancer cells.@*CONCLUSION@#The decellularized ECM scaffolds prepared using human cervical carcinoma tissues provide the basis for construction of in vitro 3D culture models for human cervical cancer cells.

Clinicopathological features of olfactory carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnosis of olfactory carcinoma (OC). Methods: Twenty-one cases of sinonasal tumors, including those initially diagnosed as olfactory neuroblastoma (ONB) and those with uncertain diagnosis, were collected from the Department of Pathology, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2016 to August 2022, among which 3 cases were reclassified as OC. The clinicopathological features were investigated, and the remaining 18 cases were used as control. Results: Of the three OC patients, 2 were male and 1 was female, with an average age of 57 years ranging from 35 to 74 years. Microscopically, the tumor cells were arranged in solid, nested or lobulated patterns with occasional palisading around the solid nests. The stroma was highly vascular with focal neurofibrillary areas. There were prominent rosettes or pseudorosettes formation. The tumor cells were mainly ovoid to spindly with scant to moderate amount of cytoplasm, one or several small nucleoli, and fine chromatin content. Brisk mitotic figures were seen. In all 3 cases of OC, there were scanty atypical glands and some were ciliated. Immunohistochemically, at least one epithelial marker and neuroendocrine marker were diffusely expressed in the tumor. Some of the tumor cells were positive for p40 and p63, and the sustentacular cells showed the expression of S-100 protein. All cases tested were negative for NUT, CD99 and desmin, with intact expression of SMARCA4 (BRG1) and SMARCB1 (INI-1). Ki-67 proliferation index varied from 20% to 80%. Follow-up after 16-18 months showed no mortality with tumor recurrence from 1 patient after 16 months. Conclusion: OC is a rare sinonasal tumor with neuroepithelial differentiation, its histomorphology is diverse, and the combination of immunohistochemical markers is essential for appropriate diagnosis.

Primary pulmonary NUT carcinoma: a clinicopathological analysis of seven cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of primary pulmonary NUT carcinoma. Methods: A total of 7 cases of primary pulmonary NUT carcinoma were collected from Fujian Provincial Hospital (n=5), Fuzhou Taijiang Hospital (n=1) and Binzhou City People's Hospital of Shandong Province (n=1) from January 2021 to April 2023. The clinical, histopathological, and immunohistochemical features were analyzed, and NUT rearrangement were detected by fluorescence in situ hybridization (FISH) with break-apart probes. Results: Seven cases were all male with age ranging from 32 to 73 years. The main clinical manifestations were cough, expectoration and chest tightness. Microscopically, NUT carcinoma was composed of monotonous proliferation of primitive-appearing small-to-medium round cells, with few eosinophilic cytoplasm, arranged in solid sheets, nests or clusters. Abrupt keratinization was typically observed in 4 cases (4/7), with high mitotic activities and necrosis. Immunohistochemistry (IHC) showed that the tumors were positive for NUT (7/7), CK7 (4/4), CK5/6 (5/6), p40 (6/7). Ki-67 index were 30%-80%. NUT gene segregation (7/7) was detected by FISH break probes. Conclusions: Primary pulmonary NUT carcinoma is rare and highly malignant. Diagnosis depends on histopathology and IHC, with molecular detection as an adjunct for diagnosis. Pathologists should be aware of the clinicopathological characteristics to avoid misdiagnosis.

New strategies for the treatment of carcinoma of unknown primary / 中华肿瘤杂志

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo / 医学前沿

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.

Clinicodemographic and computed tomography scan findings associated with thyroid gland invasion among patients with laryngeal squamous cell carcinoma

Objective@#We aim to determine the association between preoperative CT scan findings of thyroid cartilage invasion, cricoid cartilage invasion, and paraglottic space involvement with tumor extension to the thyroid gland on final histopathology among patients with laryngeal squamous cell carcinoma (SCC) in a tertiary hospital in the Philippines.@*Methods@#Patients with histopathologically-confirmed laryngeal SCC who underwent total laryngectomy with thyroidectomy while admitted at the public ward of the Department of Otorhinolaryngology, Philippine General Hospital, from January 2013 to December 2019 were included. CT scans were reviewed by 2 blinded independent radiologists. CT scan data including subsite/s involved, thyroid cartilage/cricoid cartilage erosion, paraglottic space involvement, thyroid gland involvement, and thyroid gland involvement on final histopathology were gathered. Clinicopathologic data such as age, T Stage, early tracheostomy, and time between CT scan and surgery were also collected and analyzed. Fisher’s exact test was computed for both clinicopathologic and CT scan data with a significant value having p<0.05. Cramer’s V and phi coefficient were computed for nondichotomous and dichotomous variables, respectively. Odds ratio was also computed for dichotomous variables with p<0.05 on Fisher’s exact test.@*Results@#Fifty-nine (59) men and 4 women were included, aged 43 to 81 years old. Most patients were classified as T3 (n=18) and T4 (n=41) (total=93.7%), with most having transglottic primary tumors (n=29, 46%), and only 8 (12.7%) patients having subglottic tumor involvement on final histopathology. Thyroid cartilage erosion or invasion were noted in 63.4% (n=40) of patients’ CT scans and 58.7% (n=37) of patients’ final histopathology reports. Cricoid cartilage and paraglottic space involvement were often not reported on final histopathology results. Thyroid gland involvement was only noted in the final histopathology reports of 5 patients (7.9%). Significant association between cricoid cartilage findings (p=0.032, Cramer’s V=0.318) or thyroid gland involvement on CT scan (p=0.018, Phi=0.384; OR 13 95% CI 1.797, 94.035) with thyroid gland involvement on final histopathology was noted. The rest of the variables had no significant association with thyroid gland involvement on final histopathology.@*Conclusion@#Cricoid cartilage involvement (erosion or invasion) and thyroid gland involvement on CT scan are associated with thyroid gland involvement on final histopathology in patients with laryngeal SCC. Patients with these CT scan findings may stand to benefit more from thyroidectomy to ensure good margins of resection.

Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

Clinicopathological characteristics of gastric SMARCA4-deficient undifferentiated/rhabdoid carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.

Clinicopathological features of gastric carcinomas with NTRK-rearrangement/amplification: report of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.

Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma / 南方医科大学学报

OBJECTIVE@#To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM).@*METHODS@#We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient.@*RESULTS@#In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05).@*CONCLUSION@#ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.

Immune checkpoint inhibitors for the treatment of non-small cell lung cancer brain metastases / 中华医学杂志(英文版)

Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ . Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.