Small Cell Carcinoma Research Articles

Cytomorphologic analysis of pulmonary neuroendocrine tumors – The physical effect of abrasion and aspiration on cytomorphology

Neuroendocrine tumors of the lung display characteristic cytomorphologic features allowing direct diagnosis. The specificity of these features in distinguishing subtypes of neuroendocrine tumors, and their differences among types of cytologic specimen poses as interpretative potential pitfalls. This study reviewed and compared bronchial, effusion fluid and fine-needle aspiration cytology specimens of neuroendocrine tumors of the lung to address these issues. Histology-proven cytology specimens of neuroendocrine tumors were reviewed for cytomorphological parameters focusing on reported specific neuroendocrine nuclear and background features. Totally, 46 cases (26 bronchial, 11 effusion and 9 aspirate specimens), corresponding to 37 small cell carcinomas, 7 neuroendocrine carcinomas and 2 carcinoids were reviewed. Nuclear moulding (n = 35/37, 95 %), naked nuclei (n = 33/37, 89 %) and marked nuclear irregularity (n = 32/37, 86 %) were the three most common features of small cell carcinoma. The only specific feature for small cell carcinoma was the lack of prominent nucleoli (p = 0.004). For pulmonary carcinoids, in addition to the above features, other features associated with neuroendocrine carcinoma reviewed including crush artifact and necrotic material were absent. Compared to bronchial and aspiration cytology, crush artifact (p < 0.001) and necrotic material (p = 0.014) were absent on effusion fluid specimens and naked nuclei were less frequently seen (p = 0.022), while prominent nucleoli were more often observed (p = 0.005). Nuclear moulding, irregularity and naked nuclei are common but not unique features to small cell carcinomas. Effusion fluid specimens have “cleaner” backgrounds while displaying greater nuclear atypia. The type of cytologic preparation/specimen is an important factor which must be considered during diagnostic interpretation.

Identification of HEPACAM2 as a novel and specific marker of small cell carcinoma

Identification of <i>HEPACAM2</i> as a novel and specific marker of small cell carcinoma

Metabolomic Profiling of Pulmonary Neuroendocrine Neoplasms.

Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs.

Prognostic impact of interstitial lung disease on pulmonary high-grade neuroendocrine carcinoma

Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD’s prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients’ mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy’s limited availability for recurrence and the development of acute exacerbations associated with ILD.

Revisiting ALK (D5F3) immunohistochemistry: Insights into focal staining and neuroendocrine differentiation.

Screening for anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) is crucial for identifying patients eligible for targeted therapy. The FDA-approved ALK (D5F3) immunohistochemistry (IHC) assay, used with the OptiView Amplification Kit, demonstrates excellent sensitivity and specificity in detecting these patients. However, the clinical significance of resulting focal positivity remains unclear, and ALK (D5F3) expression unrelated to ALK fusion is observed in some cases of neuroendocrine differentiation. This study aims to validate these findings with molecular testing and contribute to the accurate interpretation of ALK (D5F3) IHC results. A total of 1619 patients diagnosed with NSCLC and neuroendocrine carcinoma were evaluated using ALK (D5F3) IHC. For cases with strong but focal expression and those with diffuse strong positivity in neuroendocrine differentiation, ALK fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) tests were performed. Seven out of 1109 adenocarcinomas (0.6%) and six out of 289 squamous cell carcinomas (2.1%) exhibited strong focal ALK (D5F3) expression. Nine out of 209 neuroendocrine carcinomas (4.3%) showed homogeneously strong ALK (D5F3) expression. All these cases, including adenocarcinoma with neuroendocrine differentiation and combined small cell carcinoma, were negative for ALK fusions by FISH and/or NGS. This study demonstrates that strong but focal ALK (D5F3) immunostaining and strong expression in neuroendocrine differentiation may not indicate ALK fusion. By considering these findings, we can improve the accuracy of patient selection for targeted therapy by minimizing false-positive interpretations of ALK (D5F3) staining.

EP362 - Small Cell Ca of the Gall Bladder: A rare tumour of the gall bladder

Abstract Small cell carcinoma (SCC) of the gallbladder is an extremely rare tumour. Despite aggressive and varied treatments, its prognosis is poor. A 53/F presented with complaints of pain in abdomen and fever since 3 days. Patient was vitally stable and tenderness present over the epigastric, Right hypochondrium and Right lumbar region. Except leucocytosis, all labs were WNL. CECT Abdomen pelvis was suggestive of suspicious Gall bladder perforation with necrotic lymph nodes in the peri-pancreatic region. The patient was taken for exploratory laparotomy and a perforated gall bladder was seen intra op and cholecystectomy was performed. Histopathology findings were suggestive of small cell carcinoma - gall bladder and IHC markers (Synaptophysin, CD56, Ki67, EMA, CK19) sent for confirmatory findings were raised. Post op PET CT shows periportal, paracaval and aortocaval metastatic lymph nodes. Chemotherapy regimen (cisplatin + itoposide) was started post op and patient is under follow up. The incidence of SCC of the GB is approximately 0.5% of all GB cancers. Among NETs of the gastrointestinal tract, SCC of the GB compromises 0.2%. Less than 100 cases of this tumour have been documented in the English literature. Surgery is the mainstay of GB cancer treatment. Due to poor prognosis of SCC of the GB, even when curative surgery is possible, additional treatment methods such as chemoradiation should be considered.

Occipital condyle syndrome due to small-cell lung carcinoma: A case report.

Skull base metastases, including those from small-cell lung carcinoma (SCLC), can present with various syndromes depending on the site of involvement, such as orbital syndrome, parasellar syndrome, middle fossa syndrome, jugular foramen syndrome, and occipital condyle syndrome (OCS). One such example is OCS, which consists of unilateral occipital headache accompanied with ipsilateral hypoglossal palsy. This case report describes a 51-year-old man initially diagnosed with OCS, which led to the discovery of systemic bone metastases from SCLC. Magnetic resonance imaging showed lesions in the occipital condyle and hypoglossal canal, while positron emission tomography-computed tomography identified a lung mass and widespread metastases. SCLC is highly aggressive and metastatic, with the bone being a common site of spread. In this case, the OCS preceded the diagnosis of the underlying malignancy. Prompt diagnosis and treatment are crucial, as patients with OCS often have advanced disease. This case highlights the importance of considering SCLC as a potential etiology for OCS, given the propensity for bone metastases. Early recognition and evaluation of OCS is essential to initiate appropriate management.

Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases.

Insulinoma-associated protein 1 (INSM1) immunohistochemistry has been established as a sensitive and reliable immunohistochemical marker for detecting neuroendocrine differentiation in tumors across various organ systems. However, this marker has not been adequately investigated in primary thymic neuroendocrine tumors. We have studied a series of 27 cases of primary neuroendocrine carcinomas of the thymus, including 3 typical carcinoids, 18 atypical carcinoids, 4 large cell neuroendocrine carcinomas, and 2 small cell carcinomas. Immunostaining on whole tissue sections for INSM-1 was evaluated. Results of immunostaining for chromogranin and synaptophysin were also evaluated. 26/27 tumors (96%) demonstrated nuclear positivity for INSM1. 18 tumors (67%) showed strong and diffuse nuclear staining (3 +), 3 tumors (11%) moderate (2 +) nuclear staining, and 5 tumors (19%) showed weak (1 +) nuclear staining. The average percentage of tumor cells positive for INSM1 was 76%. Only one tumor, a small cell carcinoma, was negative. All tumors were positive for synaptophysin, and 26/27 (96%) were positive for chromogranin A. This study confirms that INSM1 immunohistochemistry is a sensitive marker of neuroendocrine differentiation in primary thymic neuroendocrine neoplasms and demonstrates similar performance characteristics compared to other organ systems. The nuclear staining with this marker offers the advantage of eliminating some of the ambiguity in the interpretation sometimes encountered with other markers. An added advantage is the consistent staining across the entire spectrum of neuroendocrine tumors of this organ.

Aberrant SWI/SNF Complex Members Are Predominant in Rare Ovarian Malignancies-Therapeutic Vulnerabilities in Treatment-Resistant Subtypes.

SWI/SNF (SWItch/Sucrose Non-Fermentable) is the most frequently mutated chromatin-remodelling complex in human malignancy, with over 20% of tumours having a mutation in a SWI/SNF complex member. Mutations in specific SWI/SNF complex members are characteristic of rare chemoresistant ovarian cancer histopathological subtypes. Somatic mutations in ARID1A, encoding one of the mutually exclusive DNA-binding subunits of SWI/SNF, occur in 42-67% of ovarian clear cell carcinomas (OCCC). The concomitant somatic or germline mutation and epigenetic silencing of the mutually exclusive ATPase subunits SMARCA4 and SMARCA2, respectively, occurs in Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), with SMARCA4 mutation reported in 69-100% of SCCOHT cases and SMARCA2 silencing seen 86-100% of the time. Somatic ARID1A mutations also occur in endometrioid ovarian cancer (EnOC), as well as in the chronic benign condition endometriosis, possibly as precursors to the development of the endometriosis-associated cancers OCCC and EnOC. Mutation of the ARID1A paralogue ARID1B can also occur in both OCCC and SCCOHT. Mutations in other SWI/SNF complex members, including SMARCA2, SMARCB1 and SMARCC1, occur rarely in either OCCC or SCCOHT. Abrogated SWI/SNF raises opportunities for pharmacological inhibition, including the use of DNA damage repair inhibitors, kinase and epigenetic inhibitors, as well as immune checkpoint blockade.

POU4F3 Is a Sensitive and Specific Marker of Merkel Cell Carcinoma

Although of therapeutic importance, a single sensitive and specific immunostain to distinguish Merkel cell carcinoma (MCC) from mimics is not currently available. In addition, single tumor cells are difficult to detect in sentinel lymph node biopsy. Leveraging publicly available data sets of 9264 solid tumors and >600,000 single-cell transcriptomes, we identified POU4F3 to be a specific marker of MCC. Analyses of Pan-Cancer RNA bulk sequencing data of 24 tumor types from Tumor Cancer Genomic Atlas data sets as well as non-Tumor Cancer Genomic Atlas small cell lung carcinoma and MCC data sets confirmed POU4F3 specificity for MCC. Single-cell RNA-sequencing analyses also confirmed the lack of POU4F3 expression in lung small cell carcinoma as well as a variety of normal tissues. Nuclear POU4F3 immunohistochemical expression was noted in 98.7% of 153 MCCs and in only 1.7% of mimics (3 of 180 cases, including 95 small cell carcinomas, of which 55 were from lungs and the remainder from other sites). Three POU4F3-positive non-MCC cases were from lungs (2 cases) and vagina (1 case). All 153 tested MCC cases were negative for ASCL1, a key transcriptional regulator highly expressed in small cell lung carcinoma. NeuroD1 was seen in a subset of MCC cases (20.9%, 32/153). POU4F3 immunostain was performed on 29 sentinel lymph nodes, and strong POU4F3 nuclear expression facilitated the ease of metastasis detection, even single tumor cells. Our study built on prior works shows that POU4F3 is a sensitive and specific clinical marker of MCC.

Patient-derived organoids and mini-PDX for predicting METN375S-mutated lung cancer patient clinical therapeutic response

Lung cancer as a molecularly and histologically high heterogonous disease, there is an urgent need to predict lung cancer patients' responses to anti-cancer treatment, and patient-derived organoids (PDOs) have been recognized as a valuable platform for preclinical drug screening. In this study, we successfully established 26 PDO lines from various subtypes of lung cancers including benign tumor, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large-cell carcinoma, and small-cell carcinoma. These PDOs were shown to retain the major genomic and histological characteristics of primary tumors and remain stable during long-term culture. With the help of targeted genomic sequencing, we found that lung cancer that harbors METN375S mutation is selectively sensitive to afatinib, and a combination of afatinib and gemcitabine induced synthetic lethality in PDO and mini-PDX models. In summary, our findings demonstrate the potential of PDO in predicting lung cancer drug response, and reveal a promising strategy for METN375S mutant lung cancer treatment.

Co60 May be the Acceptable Alternative Radionuclides of Ir192 used in HDR Brachytherapy for the Treatment of Inoperable Carcinoma Cervix in the Treatment Modality of Concurrent Chemoradiation

Background: Cancer of the uterine cervix is the eighth most common cancer among women worldwide and third among all malignancies and the second most common cancers in female in Bangladesh. The treatment of cervical cancer requires multidisciplinary approaches Concurrent chemoradiation is the treatment of choice in locally advanced carcinoma cervix uteri. Radiotherapy is the primary local treatment for most patients having FIGO stage IIB to IVA diseases. The success of treatment depends on a careful balance between EBRT and Brachytherapy that optimizes the dose to tumor. Iridium192 is highly used radionuclide for modern remote after loading HDR brachytherapy till date. Recently Co60 source is available with miniature size and identical physical properties for remote after loaders. Methods: 60 patients with biopsy proven locally advanced carcinoma of the uterine cervix were enrolled in the study. Arm A was formed comprising 30 patients who were treated by Ir192 HDR brachytherapy and Arm B formed with equal number of 30 patients who received HDR brachytherapy treated with Co60 radionuclide. This prospective observational study was carried out to compare the treatment effect between two Arm. Results: 60 patients were enrolled in this study with age range from 35 to 63 years. Most of the patients presented with stage IIB disease, consisting of 39 patients (65.3%). Among them 48 patients had squamous cell carcinoma (80.60%), adenocarcinoma trailing with 9 patients (15.3%) and rest were adenoidsquamous carcinoma 2 and small cell carcinoma. In all three insertions, urinary bladder dose distribution was slightly smaller by HDR Co60 irradiation than HDR Ir192 exposure. These differences were statistically significant in first two insertions but not in third one Conclusion: In this study radiation dose distribution at OARs i.e. urinary bladder and rectum were compared between Arm A and Arm B. In all three insertions in urinary bladder the mean dose distribution was slightly smaller in HDR Co60 irradiation than HDR Iridium192 exposure. These differences were statistically significant in first two insertions but not in third one. In case of rectum point, the mean dose distribution was significantly lower in all three insertions of Co60 exposure than Ir192 exposure.

The relationship between lobar distribution and primary lung cancer histological types

Background: Lung cancer is the primary cause of cancer-related deaths globally. Accurate tumor location and subtype characterization are critical for optimizing treatment and predicting outcomes. This study aims to identify the relationship between lobar distribution and primary lung cancer histological types and describe the most recent patterns at the country-level origin. Methods: This cross-sectional study was conducted at a major tertiary care hospital in Bangladesh, including 165 patients recruited using purposive non-probability sampling. Data were collected using a semi-structured case record form and analyzed using SPSS version 28.0. Results: Tumors were most commonly found in the central area (58.2%). Squamous cell carcinoma was the most prevalent type (46.1%), followed by adenocarcinoma (38.8%), small cell carcinoma (13.9%), and large cell carcinoma (1.2%). The incidence of squamous cell carcinoma was significantly higher in the upper lobe of the right lung (55.9%) compared to other forms, particularly in the central region of the right lung (P &lt; 0.001). Squamous cell carcinoma was more common in the lower part of the left lung (42.9%), while adenocarcinoma was exclusively observed in the lingular portion of the left lung (100%). The major bronchus of the left lung primarily exhibited squamous cell carcinoma (60%), but this finding was not statistically significant (p=0.899). Conclusion: The study highlights the significant association between lobar distribution and histological types of primary lung cancer, emphasizing the need for precise tumor characterization for better treatment strategies and prognostic evaluation.

Assessing treatment effects with adjusted restricted mean time lost in observational competing risks data

BackgroundAccording to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment.MethodsWe construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve.ResultsThe simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period.ConclusionsWe propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data.

Rare Case Report of Primary Small Cell Carcinoma of the Bladder

Small cell bladder carcinoma (SCBC) is a very rare entity. Compared to urothelial carcinoma they are more aggressive and have higher probabilities for metastases. Due to the aggressive nature of small cell bladder cancer, early diagnosis and treatment is imperative for the greatest chance of survival. We had two cases of non metastatic Small cell bladder carcinoma presenting at our institute and both were treated with definitive radiotherapy. One patient on follow up developed skeletal metastases and succumbed to disease, while the other patient is alive and disease free after 6 years. Here we present the challenges in diagnosis and treatment, and outcome of two SCBC patients treated at our institute.

Prognostic Nomogram Predicting Survival and Propensity Score Matching with Demographics and Comparative Analysis of Prostate Small Cell and Large Cell Neuroendocrine Carcinoma.

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences between common types of prostate cancer with comparative analysis for survival. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Cox proportional hazards and chi-squared analysis were used for statistical analysis. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was 71.5 years, and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasian (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year OS for Caucasians was 7.3% (95% C.I. 6.0-8.3). For Black Americans, the 5-year OS was 11.9% (95% C.I. 7.3-16.5). For Hispanics, the 5-year OS was 12.2% (95% C.I. 7.7-16.7). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. The nomogram also indicated a slight increase in mortality with tumors of greater size. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients with stage 3 tumors, as well as patients who underwent surgery and radiation. Furthermore, we performed propensity score matching for survival differences, and no survival difference was found between SCNEC and LCNEC. Conclusions: Asian patients, larger tumor size, and distant disease were associated with worse long-term clinical outcomes. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging oncology arena.

Clinical protocol phase II study of tumor infiltrating lymphocytes in advanced tumors with alterations in the SWI/SNF complex: the TILTS study.

The SWI/SNF complex is a chromatin remodeling complex comprised by several proteins such as SMARCA4 or SMARCB1. Mutations in its components can lead to the development of aggressive rhabdoid tumors such as epithelioid sarcoma, malignant rhabdoid tumor or small cell carcinoma of the ovary hypercalcemic type, among others. These malignancies tend to affect young patients and their prognosis is poor given the lack of effective treatments. Characteristically, these tumors are highly infiltrated by TILs, suggesting that some lymphocytes are recognizing tumor antigens. The use of those TILs as a therapeutic strategy is a promising approach worth exploring. Here, we report the clinical protocol of the TILTS study, a Phase II clinical trial assessing personalized adoptive cell therapy with TILs in patients affected by these tumor types.Clinical Trial Registration: 2023-504632-17-00 (www.clinicaltrialsregister.eu) (ClinicalTrials.gov).

MR imaging diagnosis of small-cell carcinoma of the ovary, hypercalcemic type: A case report and literature review.

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and aggressive gynecological tumor. We retrospectively analyzed the clinical manifestations and imaging findings of this patient and analyzed the relevant literature, with the aim of improving the ability of radiologists to differentiate SCCOHT from other ovarian tumors. We report a case of 36-year-old woman who was diagnosed with SCCOHT. MRI suggested a malignant tumor of the left ovary. The immunohistochemical markers shows SMARCA4 negativity. Notably, hypercalcemia was not detected. Microscopically, it was consistent with the large-cell variants. Despite its rarity, SCCOHT should still be considered in the differential diagnosis of ovarian malignancies. When a young female patient presents with a large unilateral tumor on MRI with a predominant solid component and significant enhancement on the contrast enhanced scans, along with hypercalcemia, SCCOHT should be considered.

PAX8 expression in cancerous and non-neoplastic tissue: a tissue microarray study on more than 17,000 tumors from 149 different tumor entities

PAX8 plays a role in development of the thyroid, kidney, and the Wolffian and Mullerian tract. In surgical pathology, PAX8 immunohistochemistry is used to determine tumors of renal and ovarian origin, but data on its expression in other tumors are conflicting. To evaluate PAX8 expression in normal and tumor tissues, a tissue microarray containing 17,386 samples from 149 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PAX8 results were compared with previously collected data on cadherin 16 (CDH16). PAX8 positivity was found in 40 different tumor types. The highest rate of PAX8 positivity was found in thyroidal neoplasms of follicular origin (98.6–100%), gynecological carcinomas (up to 100%), renal tumors (82.6–97.8%), and urothelial neoplasms (2.3–23.7%). Important tumors with near complete absence of PAX8 staining (< 1%) included all subtypes of breast cancers, hepatocellular carcinomas, gastric, prostatic, pancreatic, and pulmonary adenocarcinomas, neuroendocrine neoplasms, small cell carcinomas of various sites, and lymphomas. High PAX8 expression was associated with low tumor grade in 365 non-invasive papillary urothelial carcinomas (p < 0.0001) but unrelated to patient outcome and/or tumor phenotype in clear cell renal cell carcinoma, high-grade serous ovarian cancer, and endometrioid endometrial carcinoma. For determining a renal tumor origin, sensitivity was 88.1% and specificity 87.2% for PAX8, while sensitivity was 85.3% and specificity 95.7% for CDH16. The combination of PAX8 and CDH16 increased specificity to 96.8%. In conclusion, PAX8 immunohistochemistry is a suitable diagnostic tool. The combination of PAX8 and CDH16 positivity has high specificity for renal cell carcinoma.

Clinical Presentation and Treatment Strategies for Laryngeal Neuroendocrine Carcinoma: Insights from a Rare Case

Intriduction -Neuroendocrine neoplasms (NEN) of the larynx are very rare, accounting for &lt;1% of all laryngeal carcinomas. Based on the 2022 IARCH/WHO classification, NENs are characterised as well-differentiated neuroendocrine tumours (NET), which can further be divided into grades 1-3 based on Ki-67 levels and mitotic count, or poorly differentiated neuroendocrine carcinomas (NEC) consisting of small cell carcinoma and large cell carcinoma. In this case report, we describe a rare presentation of NEC of the larynx encountered in a 54-year-old man and how diagnostic and therapeutic dilemmas unfolded. Case description: A 6-month history of breathing and swallowing difficulties led to a tracheostomy due to stridor, in the emergency department. Imaging revealed a soft tissue mass involving the supraglottic larynx but no significant associated cervical lymphadenopathy. The biopsy from the growth was suggestive of poorly differentiated NEC as an AJCC stage cT3N0M0. However, there was local progression post-initial treatment with vincristine, doxorubicin and cyclophosphamide (VAC). The chemotherapy regimen was switched to carboplatin and etoposide. The patient received definitive radiation therapy and completed the planned dose of radiation.After 10 months of disease-free interval, there was local recurrence with lung nodules that prompted rechallenge with platinum and etoposide. The patient is doing well and remains clinically and radiologically stable to maintenance therapy with carboplatin &amp; etoposide. Conclusion: NENs of the larynx and especially NECs, are difficult to diagnose as they are rare and have varied molecular profiles. Its management frequently calls for multimodal approaches with chemotherapy and radiation therapy. Due to the developments in diagnostic and therapeutic modalities, our knowledge of NENs has been enhanced which contributed to better practice standards. Nevertheless, standardized treatment strategies remain to be determined by large cohort studies and comprehensive molecular profiling that can determine improved clinical outcomes.