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Background: Spindle cell carcinoma is a rare biphasic malignancy consisting of epithelial and mesenchymal components. It is a poorly differentiated variant of squamous cell carcinoma accounting for less than 2% of intraoral tumours, with only 69 cases reported in the literature. Clinical presentation may vary from exophytic tumours to infiltrating ulceration in the oral mucosa. Atypical presentation and erractic behaviour of these tumours mean management can be challenging, therefore prompt diagnosis and treatment are required to address the significant morbidity and mortality associated with this disease. Case Presentation: A 49‐year‐old patient presented to the oral medicine clinic reporting pain affecting the left side of their palate and cheek. Prior to their attendance, they were assessed by their general medical practitioner and neurologist; however, a trial of various medications resulted in no improvement in their symptoms. Intra‐oral examination revealed an ulcer in the left hard palate with underlying visible maxillary bone. A subsequent biopsy confirmed the diagnosis of spindle cell carcinoma, and the patient received radiotherapy with adjuvant chemotherapy. Further imaging revealed distant metastasis in the right lung and treatment was changed to palliative immunotherapy. Follow‐up imaging has shown lung nodules to be stable, and the patient remains under review with the regional head and neck cancer team. Conclusions: We report a rare case of intra‐oral spindle cell carcinoma diagnosed from a palatal lesion, which has only been reported in four cases previously at this site. Despite preceding encounters with multiple medical professionals, it is not clear whether an intra‐oral examination was carried out which may have established the diagnosis earlier. It emphasizes the importance of full head & neck examination, including intraoral examination in presentations of unexplained and intractable orofacial pain. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to report the experience of a single Portuguese oncology center in the management of patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). Methods: This is a retrospective analysis of all patients with RCC and VTT surgically treated in our center between 2008 and 2023. Only patients with VTT up to level III (Mayo Clinic classification) were included. Patient, tumor characteristics and peri-operative outcome data were registered. Administration of systemic therapy was performed upon progression. Survival analysis was conducted with the collected data. Results: A total of 64 patients (n = 16 women) were included in this study. The mean age at diagnosis was 66.3 ± 10.7 years old. The VTT level was 0, I, II and III in 40 (62.5%), 12 (18.7%), 6 (9.4%) and 6 (9.4%) patients, respectively. Nine patients (14.1%) had distant metastasis at diagnosis. No peri-operative deaths occurred, and the major complication rate was 3.1%. Histology revealed 98.4% of clear cell RCC, with sarcomatoid differentiation present in 12.5% of the cases. A negative margin status was achieved in 54 (84.4%) patients. Systemic therapy was administered in 24 (37.5%) patients during follow-up. The median progression-free (PFS), cancer-specific (CSS) and overall (OS) survival were 23, 60 and 48 months, respectively. In multivariable analysis, significant predictors of CSS were tumor size, sarcomatoid differentiation and collecting system invasion. Conclusions: Radical nephrectomy with VTT excision up to level III is a feasible and safe procedure. Patients with large tumor size, sarcomatoid differentiation and collecting system invasion are at the highest risk and should be closely monitored. [ABSTRACT FROM AUTHOR]

Simple Summary: Although immunotherapy is well established for treating pleural mesothelioma, it has not shown a breakthrough in improving the overall survival of these patients. A detailed study of the tumor microenvironment could lead to a better understanding of the factors that influence tumor growth to optimize treatment. In our cohort, T cell infiltrate differences were strongly associated with overall survival. Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth. Methods: The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters. Results: A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (p = 0.016). The presence of PD-L1 expression had a negative effect on overall survival (p = 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (p = 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis. Conclusions: Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare epithelial tumor with a biallelic mutation involving any subunit of the SDH complex. Mostly, it has low-grade morphology and a favorable prognosis. We present a case of a 36-year-old woman with weight loss, night sweats, and symptomatic anemia. Her imaging showed a hypo-enhancing heterogeneous right renal mass with invasion of the renal vein and inferior vena cava. Microscopically, the tumor had focal low-grade areas (5%) and extensive areas with high-grade features, including rhabdoid (85%) and sarcomatoid (10%) dedifferentiation. Cytoplasmic inclusions, foci of extracellular mucin, coagulative necrosis, and inflammatory infiltrate were present. The tumor cells, including rhabdoid differentiated, were focally positive for AE1/AE3. Tumor cells showed loss of SDHB immunostaining, consistent with diagnosis. Genetics testing was recommended, but the patient expired due to metastatic carcinoma. Prior studies suggest that sarcomatoid transformation and coagulative necrosis increase the risk of metastasis by up to 70% in SDH-deficient RCC. Follow-up with surveillance for other SDH-deficient neoplasms is recommended in cases of germline mutation. Here, we report the first case of SDH-deficient RCC with concomitant rhabdoid and sarcomatoid features and a detailed review of diagnostic difficulties associated with high-grade tumors. [ABSTRACT FROM AUTHOR]

Introduction The pathologic evaluation and clinical course of cytoreductive nephrectomy after combined immuno‐oncology therapy were reviewed to understand the benefits of cytoreductive nephrectomy. Case presentation Three patients with clear cell carcinoma underwent tumor biopsy before combined immuno‐oncology therapy. Case 1 was found to have a sarcomatoid component upon nephrectomy and continued with combined immuno‐oncology therapy. Case 2 discontinued combined immuno‐oncology therapy due to adverse events but maintained tumor shrinkage. The patient was found to have viable cells in most nephrectomy specimens but has had no recurrence after combined immuno‐oncology therapy was discontinued. In case 3, the residual tumor was deemed resectable with combined immuno‐oncology therapy, and nephrectomy and metastasectomy were performed. No viable cells were observed in either specimen, and the patient has had no recurrence. Conclusion Cytoreductive nephrectomy after combined immuno‐oncology therapy may be useful to allow pathologic evaluation of treatment and provide an indicator for subsequent treatment.

Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. Patients and methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non‐urinary tract recurrence‐free survival (NUTR‐FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. Results: At median follow‐up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR‐FS were observed when TUR specimens were classified as pure‐urothelial carcinoma (UC), subtypes, DD, or non‐UC. Among 2449 patients diagnosed with pure‐UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre‐RC neutrophil–lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre‐RC neutrophil–lymphocyte ratio and pathological stage were independent prognostic factors for OS. [ABSTRACT FROM AUTHOR]

This paper reported one case patient with sarcomatoid intrahepatic cholangiocarcinoma who was treated with hepatic arterial chemoembolization(TACE) in Zhuhai Hospital Affiliated to Jinan University. After the first TACE treatment the tumor progression was evaluated and then the treatment plan was adjusted to TACE combined with PD-1 inhibitor. Currently, the patient is still under regular follow-up. For the treatment of sarcomatoid intrahepatic cholangiocarcinoma, regular follow-up and multidisciplinary treatment are still effective means to improve the prognosis. [ABSTRACT FROM AUTHOR]

Spindle cell carcinoma is a rare biphasic tumour composed of squamous cell epithelial and spindle cell mesenchymal components. This variant of squamous cell carcinoma masquerades as sarcoma with a high-risk of recurrence and metastasis. Metastatic lesions to the chest wall of squamous cell carcinoma from a distant primary are rare. The most common sites for metastasis from head and neck cancers are usually seen in the lungs, liver, bone, and brain. In this present case, the patient presented with complaints of an ulcerated mass on the left buccal mucosa with limited mouth opening. Despite wide excision of the mass and postoperative radiation, it resulted in distant metastases to the chest wall after a disease-free survival of four months. The metastasis of the chest wall appearing as red, inflamed, small, multiple, subcutaneous nodules is even rarer. The diagnosis of subcutaneous metastatic nodules of squamous cell carcinoma on Fine Needle Aspiration Cytology (FNAC) appearing in the literature is infrequent. The primary in this case was oral squamous cell carcinoma, which in follow-up after wide local excision of the mass with marginal mandibulectomy, presented as multiple inflamed appearing nodules on the chest wall. The primary site of the tumour showing classical squamous cell carcinoma and its metastatic lesion appearing on morphology as the spindle cell variant of squamous cell carcinoma are also infrequently reported in the literature. Herein, one such unusual case of subcutaneous metastasis on the chest wall cytodiagnosed on FNAC is reported.

Abstract Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.

Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes. [ABSTRACT FROM AUTHOR]

Background Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. Patients and Methods Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. Results 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for S + R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. Conclusions A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation. [ABSTRACT FROM AUTHOR]

The pathologic diagnosis of pleural mesothelioma is generally based on international guidelines, but no compulsory points based on different drugs approvals in different European countries are required to be reported. According to the last (2021) edition of the World Health Organization classification of pleural tumors, the nuclear grade of epithelioid-type mesothelioma should be always inserted in the pathologic report, while the presence of BRCA-associated protein-1 (BAP1) (clone C4) loss and a statement on the presence of the sarcomatoid/nonepithelioid component are fundamental for both a screening of patients with suspected BAP1 tumor predisposition syndrome and the eligibility to perform first-line immunotherapy at least in some countries. Several Italian experts on pleural mesothelioma who are deeply involved in national scientific societies or dedicated working groups supported by patient associations agreed that the pathology report of mesothelioma of the pleura should always include the nuclear grade in the epithelioid histology, which is an overt statement on the presence of sarcomatoid components (at least 1%, in agreement with the last classification of pleural mesothelioma) and the presence of BAP1 loss (BAP1-deficient mesothelioma) or not (BAP1-retained mesothelioma) in order to screen patients possibly harboring BAP1 tumor predisposition syndrome. This review aims to summarize the most recent data on these three important elements to provide evidence regarding the possible precision needs for mesothelioma. [ABSTRACT FROM AUTHOR]

The role of neoadjuvant chemotherapy (NAC) for variant histology (VH) bladder cancer remains incompletely defined and we sought to determine comparative pathologic downstaging at radical cystectomy following NAC for patients with and without VH. Patients from 2 large tertiary care centers were matched 2:1 (437 non-VH patients, 225 VH patients). Our results showed that NAC was associated with increased likelihood of downstaging in the overall cohort and this effect was not modified by VH versus non-VH histology. Therefore, VH patients should not be excluded from NAC if otherwise eligible. Introduction: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. Patients and Methods: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cTstage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. Results: 225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). Conclusion: When comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate current first-line treatment strategies in advanced or metastatic renal cell carcinoma (RCC), and to review other promising treatments under investigations. Materials and methods: We reviewed all relevant pivotal first-line systemic therapy trials, and studies investigating the role of cytoreductive nephrectomy, metastectomy, and ablative radiotherapy in advanced or metastatic RCC. Results: In total we identified 21 relevant studies, investigating both systemic and non-systemic therapies, including treatments under investigations. Conclusion: Metastatic RCC (mRCC) is a highly heterogeneous disease that is notoriously difficult to treat, however, the discovery of novel targeted therapies over the past decade have revolutionised its management. The International mRCC Database Consortium (IMDC) is a prognostic model that is commonly used in both clinical trials and routine clinical care to risk-stratify patients with mRCC, which has helped with therapy selection for mRCC patients over the past decade. However, with an improved understanding of tumour biology and genetics, this has prompted a shift from cytokine therapy to receptor tyrosine kinase inhibitors, and now to Immune Checkpoint Inhibitors (ICIs). Recent promising results from clinical studies with ICI combination treatments have transformed the treatment landscape for the management of intermediate- and poor- risk clear cell RCC, however, further research is still needed for favourable-risk, and non-clear cell patients. Level of evidence: Not applicable [ABSTRACT FROM AUTHOR]

Spindle cell carcinoma is a rare biphasic tumour composed of squamous cell epithelial and spindle cell mesenchymal components. This variant of squamous cell carcinoma masquerades as sarcoma with a high-risk of recurrence and metastasis. Metastatic lesions to the chest wall of squamous cell carcinoma from a distant primary are rare. The most common sites for metastasis from head and neck cancers are usually seen in the lungs, liver, bone, and brain. In this present case, the patient presented with complaints of an ulcerated mass on the left buccal mucosa with limited mouth opening. Despite wide excision of the mass and postoperative radiation, it resulted in distant metastases to the chest wall after a disease-free survival of four months. The metastasis of the chest wall appearing as red, inflamed, small, multiple, subcutaneous nodules is even rarer. The diagnosis of subcutaneous metastatic nodules of squamous cell carcinoma on Fine Needle Aspiration Cytology (FNAC) appearing in the literature is infrequent. The primary in this case was oral squamous cell carcinoma, which in follow-up after wide local excision of the mass with marginal mandibulectomy, presented as multiple inflamed appearing nodules on the chest wall. The primary site of the tumour showing classical squamous cell carcinoma and its metastatic lesion appearing on morphology as the spindle cell variant of squamous cell carcinoma are also infrequently reported in the literature. Herein, one such unusual case of subcutaneous metastasis on the chest wall cytodiagnosed on FNAC is reported. [ABSTRACT FROM AUTHOR]

ObjectivesTo study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805.Patients and methodsThe original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805.ResultsA total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo).ConclusionsAdjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.

Objective: To evaluate post‐nephrectomy outcomes and predictors of cancer‐specific survival (CSS) between patients with localised sarcomatoid renal cell carcinoma (sRCC) and those with Grade 4 RCC (non‐sRCC), as most sRCC research focuses on advanced or metastatic disease with limited studies analysing outcomes of patients with localised non‐metastatic sRCC. Patients and Methods: A total of 564 patients with localised RCC underwent partial or radical nephrectomy between June 1988 to March 2019 for sRCC (n = 204) or World Health Organization/International Society of Urological Pathology Grade 4 non‐sRCC (n = 360). The CSS at every stage between groups was assessed. Phase III ASSURE clinical trial data were used to externally validate the CSS findings. The Mann–Whitney U‐test and chi‐squared test compared outcomes and the Kaplan–Meier method evaluated CSS, overall survival (OS) and recurrence‐free survival. Clinicopathological features associated with RCC death were evaluated using Cox proportional hazards regression. Results: The median follow‐up was 31.5 months. The median OS and CSS between the sRCC and Grade 4 non‐sRCC groups was 45 vs 102 months and 49 vs 152 months, respectively (P < 0.001). At every stage, sRCC had worse CSS compared to Grade 4 non‐sRCC. Notably, pT1 sRCC had worse CSS than pT3 Grade 4 non‐sRCC. Negative predictors of CSS were sarcomatoid features, non‐clear cell histology, positive margins, higher stage (pT3/pT4), and use of minimally invasive surgery (MIS). ASSURE external verification showed worse CSS in patients with sRCC (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.12–2.36; P = 0.01), but not worse outcomes in MIS surgery (HR 1.39, 95% CI 0.75–2.56; P = 0.30). Conclusions: Localised sRCC had worse CSS compared to Grade 4 non‐sRCC at every stage. Negative survival predictors included positive margins, higher pathological stage, use of MIS, and non‐clear cell histology. sRCC is an aggressive variant even at low stages requiring vigilant surveillance and possible inclusion in adjuvant therapy trials. [ABSTRACT FROM AUTHOR]

Introduction: Sarcomatoid differentiation has been reported in approximately 8% of chromophobe renal cell carcinoma (RCC) and is associated with a worse prognosis. We aim to describe the clinicopathologic and molecular findings of chromophobe RCC with sarcomatoid differentiation. Methods: Surgical pathology database was searched to identify chromophobe RCC with sarcomatoid differentiation from January 2015 to December 2021. Results: Five patients were diagnosed with chromophobe RCC with sarcomatoid differentiation. The median age at the time of diagnosis was 57 years (range 51-61 years). Three patients died after median follow-up of 12.1 months (range 1.6-18.2 months). The median tumor size was 10.7 cm (range 5.6-13.6 cm). The median percentage of sarcomatoid component was 60% (range 10-90%), and the median percentage of necrosis was 30% (range 10-50%). One tumor demonstrated osteoid formation. PAX8, keratin 7, KIT (CD117), and Hale colloidal iron were positive in the epithelial component, whereas the sarcomatoid component was positive for vimentin, CD10, and high Ki67 proliferative index. Molecular testing was performed in three specimens: all were TP53 mutated and microsatellite stable. One aggressive tumor had RB1 frameshift mutation and copy number gains for TERT and CUL4A. Conclusion: Chromophobe RCC with sarcomatoid differentiation is a rare entity with aggressive behavior. Percentage of sarcomatoid component, necrosis, and the occurrence of metastasis is associated with worse prognosis. Molecular profiling reveals frequent TP53 mutation. While TERT promoter mutation has no prognostic implication, FLCN inactivation may be associated with a less aggressive course. The clinical significance of RB1 loss is unclear. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Sarcomatoid hepatocellular carcinoma (SHCC) is a rare subtype of hepatocellular carcinoma characterized by abdominal pain or persistent fever with an inflammatory reaction. Here, we report a case of SHCC mimicking hepatic abscess described by not only ultrasonography but also computer tomography. SHCC is a rare subtype of hepatocellular carcinoma characterized by epithelial and mesenchymal tumor features with sarcomatoid morphology. Here, we report a case of SHCC described by ultrasonography and computer tomography as well as confirmed by pathological examination. [ABSTRACT FROM AUTHOR]

Aim and background: Sarcomatoid squamous cell carcinoma (SSCC) is a rare malignant variant of SCC. Here, we present a rare case of primary cutaneous SSCC of the scalp. Case description: We present a case of a 68-year-old male with a very large pedunculated left scalp mass, first noted several years ago, with rapid expansion of the mass 6 months prior to presentation. The mass was mobile of the cranium and without calvarial involvement. He successfully underwent a wide local excision of the mass with no evidence of recurrence at his 6-month follow-up visit. Conclusion: This case of primary scalp cutaneous SSCC represents a rare head and neck site of involvement. Due to the rarity of primary cutaneous SSCC and very few reports of primary cutaneous SSCC arising in the head and neck, management is guided by case series of SSCC arising in other sites. Surgical resection is the recommended primary modality of treatment, with or without regional lymphadenectomy. Adjuvant radiation therapy may be considered for larger tumors, positive lymph nodes, older age, and high-risk features. Due to the concern for a potentially high rate of recurrence, close follow-up is essential. Clinical significance: Sarcomatoid squamous cell carcinoma is a rare malignant variant of SCC that presents a significant diagnostic challenge, as it shares morphologic and immunohistochemical overlap with other spindle cell tumors. While the majority of SSCC of the head and neck occurs in mucosal sites such as the larynx, the scalp remains an extremely rare presentation, with only a few reported cases in the literature. This review of the literature and case report presents an additional case of primary cutaneous SSCC involving the scalp. [ABSTRACT FROM AUTHOR]

Sarcomatoid renal cell carcinoma (sRCC) accounts for about 4%–5% of all kidney cancers. Previous studies showed that PD-1 and PD-L1 expression was higher in sRCC compared to non-sRCC. In the present study, we aimed to investigate PD-1/PD-L1 expression and its association with clinicopathological features in sRCC. The study included 59 patients diagnosed with sRCC between January 2012 and January 2022. The expression of PD-1 and PD-L1 in sRCC was detected by immunohistochemical staining, and its correlation with clinicopathological parameters was analyzed by χ2 test and Fisher exact test. Kaplan–Meier curves and log-rank tests were used to describe the overall survival (OS). The prognostic significance of clinicopathological parameters on OS was assessed by Cox proportional hazards regression analysis. Among the 59 cases, the positive expression of PD-1 and PD-L1 was 34 cases (57.6%) and 37 cases (62.7%), respectively. PD-1 expression was not significantly correlated with any parameters. However, PD-L1 expression was significantly correlated with tumor size and pathologic T stage. OS was shorter in the subgroup of patients with PD-L1-positive sRCC compared with the PD-L1-negative subgroup. There was no statistically significant difference in OS between PD-1-positive and negative subgroups. According to our study, the univariate and multivariate analysis indicated that pathological T3 and T4 was an independent risk factor in PD-1-positive sRCC. We studied the relationship between PD-1/PD-L1 expression and clinicopathological characteristics in sRCC. The findings may provide valuable implications for clinical prediction. [ABSTRACT FROM AUTHOR]

This study evaluated the outcomes of patients with non-clear cell renal cell carcinoma (RCC) and RCC with sarcomatoid features receiving systemic treatment. We conducted a single-center retrospective analysis of 251 patients with advanced RCC receiving systemic therapy. Overall, patients with nonclear cell histology and RCC with sarcomatoid features had worse overall survival compared to those with clear cell histology. Background: Patients with nonclear cell renal cell carcinoma (RCC) and RCC with sarcomatoid differentiation have been under-represented in clinical trials. This study evaluates the outcomes and treatment patterns of patients with nonclear cell RCC and RCC with sarcomatoid features compared to those with clear cell RCC receiving systemic therapy. Methods: A single-center retrospective analysis of patients with advanced or metastatic RCC receiving systemic therapy was conducted. Patients were divided into groups based on histology: nonclear cell RCC, clear cell RCC, and RCC with and without sarcomatoid features. The primary endpoint was overall survival (OS) for each group calculated from the date of diagnosis of advanced or metastatic RCC to the date of last follow-up or death. Additionally, an exploratory analysis was conducted by nonclear cell t ype and t ype of first-line treatment. Results: Overall, 251 patients were included, with most treated before 2018. First-line therapies included vascular endothelial growth factor monotherapy (68.5%), immunotherapy monotherapy (7.6%), immunotherapy combination therapy (16.7%), or other treatments (7.2%). Overall survival was shorter for patients with nonclear cell RCC compared to clear cell RCC (39.2 months vs. 81.1 months, hazard ratio (HR), 1.60, 95% Confidence Interval 1.0, 2.6, P = .04). Additionally, OS for patients with sarcomatoid differentiation was shorter compared to patients without sarcomatoid differentiation (43.4 vs. 75.0 months, HR 1.5, 95% CI 0.8, 2.6, P = .20). Conclusion: We demonstrate inferior outcomes among patients with advanced or metastatic nonclear cell RCC and RCC with sarcomatoid differentiation receiving systemic treatment. Further prospective studies are warranted testing immunotherapy combinations and novel treatments in patients with nonclear cell RCC. [ABSTRACT FROM AUTHOR]

Malignant melanoma is an aggressive, notorious tumor showing great variability in morphological and immunohistochemical expression, thus commonly leading to an erroneous diagnosis. Within the melanoma group, amelanotic melanoma, with its wide clinical presentations, lack of pigmentation, and varied histological appearances, has taken on a new persona as a master masquerader. Use of immunohistochemistry in the diagnosis of malignant tumors, including melanoma, is primordial and indispensable. However, the problem gets compounded in scenario of aberrant antigenic expression. The present case posed multiple diagnostic challenges in form of atypical clinical presentation, variant morphology, as well as aberrant antigenic expression. Here, we present the case of a 72-year-old male who, upon his initial presentation, was thought to be sarcomatoid anaplastic plasmacytoma, but 5 months later another biopsy from a different site revealed the actual diagnosis of amelanotic melanoma.

Key Clinical Message Sarcomatoid hepatocellular carcinoma (SHCC) is a rare subtype of hepatocellular carcinoma characterized by abdominal pain or persistent fever with an inflammatory reaction. Here, we report a case of SHCC mimicking hepatic abscess described by not only ultrasonography but also computer tomography. SHCC is a rare subtype of hepatocellular carcinoma characterized by epithelial and mesenchymal tumor features with sarcomatoid morphology. Here, we report a case of SHCC described by ultrasonography and computer tomography as well as confirmed by pathological examination.

Vulvar squamous cell carcinoma with sarcomatoid features is an extremely rare histological variant of squamous cell carcinoma with co-existence of both epithelial and mesenchymal features. A 70-year-old woman presented with genital lesions for 4 months with associated burning and pain. Examination revealed well-defined bilaterally symmetrical hyperpigmented plaques on labia majora, fleshy erythematous growth on labia minora. Biopsy from the fleshy mass was suggestive of sarcomatoid malignancy. However, immunohistochemistry was positive for cytokeratin AE1/AE3 and negative for desmin and smooth muscle actin. Biopsy from hyperpigmented plaque was suggestive of Bowens disease. On the basis of histopathology and immunohistochemistry findings, diagnosis of vulvar sarcomatoid squamous cell carcinoma with Bowens disease was made and patient was started on external beam radiation therapy. Sarcomatoid squamous cell carcinoma of vulva is very rare cancer that has an aggressive and fatal course. Diagnosis has traditionally been difficult due to a large ratio of sarcomatous to squamous cell component. Due to its rarity, there are no distinct guidelines to direct therapy and care. [ABSTRACT FROM AUTHOR]

Patients with sarcomatoid renal cancer in good, intermediate and poor prognostic groups were randomized 1:1 sunitinib and gemcitabine (SG) versus sunitinib and assessed for response rate in this cooperative group phase II trial. Sunitinib but not the SG met the preset threshold of success. Grade = 3 events were seen. EA1808 was the first randomized cytotoxic trial for sarcomatoid RCC. Introduction: Sarcomatoid renal cancer (sRCC) patients have poor outcomes. EA1808 evaluated sunitinib and gemcitabine (SG) and sunitinib alone (S) in sRCC in a randomized cooperative group phase II trial (NCT01164228). Patients and Methods: Pts were aggregated 1:1 to SG (45 pts) or S (40 pts) using a 2-stage design. sRCC pts with = 1 prior nonvascular endothelial growth factor tyrosine kinase inhibitor were stratified into prognostic groups: good (clear cell, < 20% sarcomatoid, PS 0), intermediate (20%-50% sarcomatoid, PS 0), and poor (nonclear cell or > 50% sarcomatoid or PS 1). The primary endpoint was response rate (RR). For SG, the null RR was 15% and a 30% RR was of interest. For S, a 20% RR was of interest vs. a 5% null rate. Secondary endpoints were progression-free survival, overall survival, and safety. Results: Both arms met protocol cr iter ia for stage 2 of accrual. A total of 47 pts were randomized to SG and 40 to S. The SG arm had 9 of 45 evaluable patient responses (RR of 20%; CI = [13%-31%]) not meeting the predetermined threshold for success. The sunitinib arm met its endpoint with 6/37 (RR of 16%; CI = [9%-27%]) evaluable responses. Grade = 3 events were experienced by 36 in the SG arm and 17 in the sunitinib arm Conclusions: EA1808 was the largest and first randomized cytotoxic trial for sarcomatoid RCC. Sunitinib alone but not the SG met the preset threshold of success. Cytotoxic chemotherapy is only useful in limited clinical scenarios for sRCC. [ABSTRACT FROM AUTHOR]

Sarcomatoid squamous cell carcinoma is a rare variant of laryngeal carcinoma, which comprises 1.3% of all laryngeal malignancies. It is mainly seen in elderly individuals, with smoking and alcohol being common risk factors. The tumor is most common on true vocal cords; hence, patients especially present with dysphonia. We present a case of an elderly male patient who presented with dysphonia due to a vocal cord lesion. During microlaryngoscopy, a firm, exophytic lesion with a narrow stalk was attached to the anterior one-third of the right vocal cord, excised, and sent for histopathology. Histopathology was suggestive of sarcomatoid squamous cell carcinoma. The patient was successfully treated with radiotherapy. We conclude that benign-appearing laryngeal lesions need to be evaluated and histopathological examination to be performed so that rare entities such as sarcomatoid carcinoma, which mimics benign lesions, can be managed appropriately. [ABSTRACT FROM AUTHOR]

Objective: To report the oncological survival outcomes of men with penile sarcomatoid squamous cell carcinoma (sSCC). Patients and Methods: A retrospective analysis of men with penile sSCC diagnosed between January 2010 and January 2020 in a single centre was conducted. Disease‐specific (DSS), recurrence‐free (RFS) and metastasis‐free (MFS) survival were evaluated. Outcomes were compared with a non‐sarcomatoid penile SCC cohort matched to age, type of surgery and tumour stage. Kaplan–Meier plots were used to estimate survival outcomes. Results: In all, 1286 men were diagnosed with penile SCC during the study period and of these 38 (3%) men had sSCC. The median (interquartile range) age and follow‐up was 70 (57–81) years and 16 (7–44) months, respectively. Operations performed included: circumcision, one (2.6%); wide local excision, four (10.5%); glansectomy, 11 (29%); partial penectomy, 10 (26%); subtotal/total penectomy, 12 (32%). The Kaplan–Meier estimated 12‐, 24‐ and 36‐month DSS was 62% (vs non‐sarcomatoid, 67%), 43% (vs non‐sarcomatoid, 67%) and 36% (vs non‐sarcomatoid, 67%), respectively (P = 0.03). The Kaplan–Meier estimated 12‐ and 24‐month RFS was 47% (vs non‐sarcomatoid, 60%) and 28% (vs non‐sarcomatoid, 55%), respectively (P = 0.01). The MFS was 52% (vs non‐sarcomatoid, 62%) at 12 months and 37% (vs non‐sarcomatoid, 57%) at 24 months (P = 0.04). Conclusions: Sarcomatoid differentiation was associated with a lower DSS, RFS and MFS. Due to the rarity of its incidence and aggressiveness, expert histological review and multidisciplinary management is required in a specialist penile cancer centre. [ABSTRACT FROM AUTHOR]

Background: Sarcomatoid variant of squamous cell carcinoma in the oral cavity is a rare biphasic variant of squamous cell carcinoma. This aggressive variant of squamous cell carcinoma is characterized by invasive growth with marked local recurrence and distant metastasis resulting in poor prognosis. Sarcomatoid carcinoma can occur over a wide age range, incidence increases with older age and is a male-predominant disease. Methods: 23 patients with histologically proven Sarcomatoid SCC or with a sarcomatoid component (Group A) were compared with 23 randomly chosen patients with clinical stage IV (Group B) disease at the time of diagnosis, within the same time period and comparison was made between disease free survival and overall survival. Results: In group A, the mean DFS was found to be 12.4 months raging from 1 month to 36 months. 6 patients were therafter lost to follow follow up, in 11 patients the mean overall survival was found to be 8.72 months (ranging from 2 to 18 months) whereas 6 patients are alive till date. In group B, the mean DFS was found to be 19.56 months ranging from 6 months to 33 months. 4 patients succumbed to the disease with a mean overall survival of 24.25 years (ranging from 18 to 33 months), 4 patients were lost to follow up and the rest are alive till date. Conclusion: Sarcomatoid carcinoma of the oral cavity is an extremely rare but aggressive variant of conventional squamous cell carcinoma. We have to systematically understand their clinical, morphological and immunohistochemical features which is critical for their accurate diagnosis which aids in correct patient management. After radical surgery and adjuvant radiation therapy, strict follow up for development of recurrence and distant metastasis should be done. [ABSTRACT FROM AUTHOR]

Abstract Background Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy. Case presentation A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer—sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission. Conclusions The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.

Chromophobe renal cell carcinoma (CRCC) is a subtype of renal cell carcinoma (RCC) with a favorable prognosis. Sarcomatoid differentiation in RCC is assumed to be the outcome of the parent tumor's dedifferentiation and associated with poorer prognosis. Sarcomatoid differentiation can be detected in CRCC as well as other subtypes, but the occurrence of divergent osteosarcoma-like components in sarcomatoid CRCC is extremely unusual. Only six cases have been previously reported in the literature, we reviewed them and presented the seventh case in a 71-year-old male who had a left kidney heterogeneous mass. The resected tumor showed a sarcoma-like spindle cell area with an adjacent osteosarcoma area producing lacy bone material and bony trabeculae in a hard area mixed with a typical CRCC. In conclusion, sarcomatoid CRCC with osteosarcomatous differentiation is a very rare tumor and should be kept in mind especially when dealing with small or frozen sections biopsies. [ABSTRACT FROM AUTHOR]

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease. [ABSTRACT FROM AUTHOR]

Malignant melanoma is an aggressive, notorious tumor showing great variability in morphological and immunohistochemical expression, thus commonly leading to an erroneous diagnosis. Within the melanoma group, amelanotic melanoma, with its wide clinical presentations, lack of pigmentation, and varied histological appearances, has taken on a new persona as a master masquerader. Use of immunohistochemistry in the diagnosis of malignant tumors, including melanoma, is primordial and indispensable. However, the problem gets compounded in scenario of aberrant antigenic expression. The present case posed multiple diagnostic challenges in form of atypical clinical presentation, variant morphology, as well as aberrant antigenic expression. Here, we present the case of a 72-year-old male who, upon his initial presentation, was thought to be sarcomatoid anaplastic plasmacytoma, but 5 months later another biopsy from a different site revealed the actual diagnosis of amelanotic melanoma. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate MRI features of sarcomatoid renal cell carcinoma (RCC) and their association with survival. Methods This retrospective single-center study included 59 patients with sarcomatoid RCC who underwent MRI before nephrectomy during July 2003–December 2019. Three radiologists reviewed MRI findings of tumor size, non-enhancing areas, lymphadenopathy, and volume (and percentage) of T2 low signal intensity areas (T2LIA). Clinicopathological factors of age, gender, ethnicity, baseline metastatic status, pathological details (subtype and extent of sarcomatoid differentiation), treatment type, and follow-up were extracted. Survival was estimated using Kaplan-Meier method and Cox proportional-hazards regression model was used to identify factors associated with survival. Results Forty-one males and eighteen females (median age 62 years; interquartile range 51–68) were included. T2LIAs were present in 43 (72.9%) patients. At univariate analysis, clinicopathological factors associated with shorter survival were: greater tumor size (> 10 cm; HR [hazard ratio] = 2.44, 95% CI 1.15–5.21; p = 0.02), metastatic lymph nodes (present; HR = 2.10, 95% CI 1.01–4.37; p = 0.04), extent of sarcomatoid differentiation (non-focal; HR = 3.30, 95% CI 1.55–7.01; p 3.2 mL, HR = 4.22, 95% CI 1.92–9.29); p

Background: Renal cell carcinoma (RCC) is common cancer derived from the renal epithelium. One of the rarest cases of RCC is sarcomatoid RCC (sRCC). The occurrence of sRCC in animals is not clearly demonstrated. Aim: This study aimed to observe the clinicopathological characteristics of sRCC in animals from East Java, Indonesia, from 2017 to 2022. Methods: This study used patients which were histopathologically diagnosed with sRCC in our laboratory from 2017 to 2022. The data of clinical characteristics of animals, hematology, serology, histopathology, and immunohistochemistry were retrieved and tabulated. The data was qualitatively and quantitatively analyzed using a simple descriptive method and SPSS version 26, respectively. Results: Fourteen cases of sRCC in animals have been identified in this study. It was found in rodents, dogs, and cats. sRCC predominantly occurred in rodents (57.14%) without specific clinical signs. The common histopathological findings of sRCC were epithelial renal cells transition into elongated atypical spindle cells. In addition, other histopathological patterns of a renal epithelial cell such as clear cell, tubule-cystic, and papillary also have been found. Immunohistochemistry by using antibodies demonstrates that PAX8 is expressed on sRCC tissue samples 92.85% (13/14 samples). Hence, PAX8 could be used as a supporting method for establishing the diagnosis of sRCC in animals. Hematology and serological tests did not correlate to type of sRCC either pure sRCC or dedifferentiated sRCC. sRCC result in hypercreatinemia in rodents and dogs. Conclusions: This study shows that the incidence of sRCC in animals is rare. Animals with sRCC did not show any specific clinical signs. The histopathological finding is quite difficult to be differentiated from the other RCC. PAX8 expression on renal tissue samples is useful in supporting the diagnosis of sRCC in animals. [Open Vet J 2023; 13(1.000): 64-73]

Vulvar squamous cell carcinoma with sarcomatoid features is an extremely rare histological variant of squamous cell carcinoma with co-existence of both epithelial and mesenchymal features. A 70-year-old woman presented with genital lesions for 4 months with associated burning and pain. Examination revealed well-defined bilaterally symmetrical hyperpigmented plaques on labia majora, fleshy erythematous growth on labia minora. Biopsy from the fleshy mass was suggestive of sarcomatoid malignancy. However, immunohistochemistry was positive for cytokeratin AE1/AE3 and negative for desmin and smooth muscle actin. Biopsy from hyperpigmented plaque was suggestive of Bowens disease. On the basis of histopathology and immunohistochemistry findings, diagnosis of vulvar sarcomatoid squamous cell carcinoma with Bowens disease was made and patient was started on external beam radiation therapy. Sarcomatoid squamous cell carcinoma of vulva is very rare cancer that has an aggressive and fatal course. Diagnosis has traditionally been difficult due to a large ratio of sarcomatous to squamous cell component. Due to its rarity, there are no distinct guidelines to direct therapy and care.

Introduction: Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets. Case presentation: Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair– gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4 + lymphocytes and macrophages. Conclusion: We report two cases of patients cured from advanced ATC and fo r the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.

Sarcomatoid sweat gland carcinomas are rare among cutaneous cancers, with less than 20 cases described. A 54‐year‐old woman with sarcomatoid sweat gland carcinoma of the right upper extremity suffered extensive recurrence at 15 months, unresponsive to chemotherapy. There is no standard treatment or chemotherapy regimens for metastatic sweat gland carcinoma. [ABSTRACT FROM AUTHOR]

Background: Non-clear cell renal cell carcinomas are uncommon renal tumours with diverse histologically and genetically defined entities. Due to limited clinical outcomes data, no standardized management approach can be offered to these patients. This study aimed to analyse outcomes of nonclear cell renal cell carcinoma after surgical resection of localized renal tumours in our population. Methods: Patients with renal tumours who underwent partial or radical nephrectomy at the Department of Urology, from January 2010 to December 2019 were identified and evaluated, in terms of prevalence, presentation, recurrence, and survival outcome. Results: Non-clear cell tumours were found in one-fourth of the total number of nephrectomies performed during this period for renal cell carcinoma (RCC). The mean age was 50.48±14.76 years (range 18-89 years) with 57% being of the male gender. The predominant types were chromophobe RCC, papillary RCC, and sarcomatoid RCC, in all non-clear cell renal tumours. Mean Recurrence Free Survival (RFS) for all tumours was 75.26±2.7 months. The projected 5 years RFS of papillary RCC, chromophobe RCC and sarcomatoid RCC were 94.2%, 84.3% and 62.5% respectively. Conclusion: RCC of non-clear-cell histology depicts excellent survival in patients with localized renal tumours. Furthermore, sarcomatoid RCC has worse recurrence free survival followed by chromophobe RCC and papillary RCC, in our population subset. [ABSTRACT FROM AUTHOR]

Background: Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy. Case presentation: A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer—sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission. Conclusions: The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC. [ABSTRACT FROM AUTHOR]

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

Background: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. Patient and Methods: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. Results: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. Conclusion: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters.

Abstract Sarcomatoid sweat gland carcinomas are rare among cutaneous cancers, with less than 20 cases described. A 54‐year‐old woman with sarcomatoid sweat gland carcinoma of the right upper extremity suffered extensive recurrence at 15 months, unresponsive to chemotherapy. There is no standard treatment or chemotherapy regimens for metastatic sweat gland carcinoma.

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM. [ABSTRACT FROM AUTHOR]