Mucinous Tubular And Spindle Cell Carcinoma Research Articles

Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA).We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays.The cohort was comprised of 8 females and males, each, with an age range of 33–79 years (median, 59), and a tumor size range of 3.4–15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally.Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC.MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Mucinous tubular and spindle cell carcinoma of the kidney: a report of seven cases

ObjectiveTo further analyse the imaging features and tumour outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney.Materials and methodsThe current study retrospectively reviewed the clinical information of seven patients diagnosed with MTSCC at our institution from January 2011 to March 2023.ResultsThe median age at diagnosis was 52 years (range, 32–66 years) and the majority of patients were female (71.4%). On conventional abdominal ultrasound, the majority of the tumours (5/7) were heterogeneous hypoechoic or slightly hypoechoic. Colour Doppler flow imaging showed blood flow within the tumour in 2 cases and peripheral blood flow signal in 1 case. On non-enhanced CT, all tumours had a spherical or ovoid shape, with an expansile growth mode, and had clear or unclear boundaries with the surrounding renal parenchyma. The tumours were either partially exophytic (n = 4) or parenchymal (n = 3), while no cases of completely exophytic tumour was observed (n = 0). On contrast-enhanced CT, the majority of tumours (5/7) showed a heterogenous pattern of enhancement and the mean tumour diameter was 6.7 ± 4.4 cm (range, 2.1–16.8 cm). All patients underwent partial or radical nephrectomy for pT1a (42.9%), pT1b (28.5%), pT2 (14.3%) or pT3b (14.3%) stage. Among these, 1 patient (14.3%) had a level I tumour thrombus at diagnosis and died of disease 24.5 months later. The remaining patients had no recurrence or metastasis.ConclusionMTSCC is not universally indolent, which tends to occur in female patients of a broad range of ages. MTSCC is a hypovascular renal tumour, which is different from clear cell renal cell carcinoma (RCC); however, it is difficult to distinguish MTSCC from other hypovascular RCC subtypes because of the overlap of their imaging characteristics.

Mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a unique neoplasm attributing to less than 1% of all renal cell carcinoma (RCC). The median age is 6th decade with a significant female preponderance.1 These tumors classically consist of tightly packed, elongated, and anastomosing tubules which merge with bland spindle cells in a myxoid stroma in variable proportions. Tubules with tufting or small papillae and foci of foamy macrophages may occur. The tumor cells are low-grade and may show clear cytoplasm or oncocytic changes with rare mitosis. Immunohistochemically, PAX8, CK7, AMACR, and CD10 are positive in this tumor.1,2 Though it is a morphological diagnosis, it can be challenging to differentiate from a solid variant of papillary RCC, sarcomatoid RCC, or myoid-predominant angiomyolipoma. Immunohistochemistry may be of little help due to overlapping profiles.3 Copy number analyses can help establish a diagnosis in challenging cases or core biopsies since these are associated with multiple chromosomal losses involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. Novel biomarkers like VSTM2A overexpression are also emerging, which can be detected by RNA in-situ hybridization. Recurrent Hippo pathway aberrations have been defined as the molecular signature of MTSCC with increased nuclear YAP1 protein expression.4 Adverse features such as necrosis, solid growth, single file infiltration, sarcomatoid transformation, lymphovascular invasion, and increased mitoses are indicators of metastatic disease. Although it has indolent behavior, rare cases with classic morphology have been seen to develop metastases.5-6 We describe gross and histopathological findings of mucinous tubular and spindle cell carcinoma in a 65-year-old male patient. He presented with right abdominal pain for one month. The pain was dull and mild to moderate in intensity. On contrast-enhanced ultrasound, a well-defined, smoothly marginated heterogeneous hyperechoic lesion measuring 5.5x6cm was noted at the upper pole of the right kidney. The lesion was hyper enhancing compared to the rest of the renal parenchyma. Based on the radiological findings, possibilities of chromophobe RCC and oncocytoma were considered. The abdominal computed tomography (CT) revealed a hyperdense lesion in the upper pole of the right kidney with a relatively well-defined margin measuring 63x65x69mm with no evidence of significant post-contrast enhancement in the either arterial, venous or delayed phase. The patient underwent a right radical nephrectomy. On gross examination, a well-encapsulated mass was seen wholly occupying the upper pole of the kidney measuring 6.9x6.5x5.5cm. The cut surface was variegated with grey-white, firm areas admixed with mucinous and hemorrhagic foci (Figure 1A). No capsular breach or perinephric fat extension was noted. The renal pelvis, sinus, and renal vessels were free of tumor. Figure 1 A - gross nephrectomy specimen showing a large, well-demarcated tumor involving the upper pole of the kidney measuring 6.9x6.5x5.5cm. The cut surface is variegated and appears grey-white and firm, along with intervening mucinous and hemorrhagic areas (scale bar = 5 cm); B - microscopically, the tumor is well-circumscribed with sharp demarcation from adjacent normal renal parenchyma (H&E; 40x); C - the dominant epithelial component is seen against the background stroma containing significant extracellular mucin (H&E; 100x); D - higher magnification showing tightly packed anastomosing tubules lined by low-grade cuboidal cells with cytoplasmic vacuoles against mucinous background (H&E; 400x).: Microscopically, the tumor was well-demarcated from the adjacent native renal parenchyma (Figure 1B). It was composed of the dominant epithelial element against the background of extracellular mucinous stroma (Figure 1C). The epithelial component contained tightly packed, elongated, tufted, and anastomosing tubules lined by low-grade cuboidal cells and are seen merging with bland spindle cells (Figure 1D). The nuclei display fine vesicular chromatin, inconspicuous nucleoli, and moderate cytoplasm with vacuolations. Mitotic figures are infrequent (<1/10HPF). No necrosis, lymphovascular invasion, or high-grade transformation was found. However, foamy macrophage collections and lymphoid aggregates are admixed. Cholesterol clefts with focal foreign body giant cell response indicated the long-standing nature of the tumor. Based on the gross and microscopy findings, the diagnosis of mucinous tubular and spindle cell carcinoma [(pT1bpNx; American Joint Committee on Cancer (AJCC) staging manual; 8th edition)] was rendered.

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney: A Study of Clinical, Imaging Features and Treatment Outcomes.

PurposeTo describe the clinical, imaging, pathological features and oncologic outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney.Patients and MethodsTwenty-two cases of MTSCC were pathologically identified between January 2004 and April 2021 at our institution. The clinical and imaging findings, pathological features, treatment methods and outcomes of the patients were reviewed.ResultsThese cases included 17 women and 5 men, with a median age at diagnosis of 52.5 years. On contrast-enhanced CT, MTSCC was less enhanced than the adjacent renal parenchyma. Tumor attenuation values were 33.3 ± 6.8HU, 44.0 ± 9.1HU, 54.4 ± 13.9HU and 67.1 ± 11.8HU in the non-contrast, corticomedullary, nephrographic and excretory phases of CT, respectively. Contrast-enhanced ultrasonography and MRI also showed hypovascular features of the masses. On MRI, the tumors were isointense on T1-weighted images and slightly hypo- or hyperintense on T2-weighted images. Diffusion-weighted imaging revealed a low apparent diffusion coefficient of the tumor. The patients were managed with laparoscopic partial nephrectomy (n=5), radical nephrectomy (n=16), or robotic-assisted laparoscopic partial nephrectomy (n=1). The median follow-up time was 59.5 months. All the patients were free of local recurrence or distant metastasis.ConclusionsMTSCC is generally indolent and has favorable outcomes. The imaging features of MTSCC are generally hypovascular, which is significantly different from clear cell renal cell carcinoma. However, it is still difficult to distinguish MTSCC from other hypovascular renal tumors preoperatively because their imaging features overlap. Further studies are essential to fully characterize the features of this rare RCC variant.

Proteomic profiling identifies novel diagnostic biomarkers and molecular subtypes for mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that the MTSCC tumor proteome was significantly enriched in B‐cell‐mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from the solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti‐tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three‐protein diagnostic panel and molecular subtypes for MTSCC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Papillary Renal Cell Carcinoma with Extensive Spindle Cell Foci: Mimicker of Mucinous Tubular and Spindle Cell Carcinoma

Abstract Introduction/Objective Papillary Renal Cell Carcinoma (PRCC), the 2nd most common RCC, accounts for 10-15% of cases and is usually composed of tubules and papillae with foamy histiocytes in papillary cores. Mucinous tubular and spindle cell carcinoma (MTSC) is composed of tightly packed, elongated, curvilinear tubules with smooth luminal surfaces, separated by mucinous stroma. MTSC is associated with a more favorable prognosis than PRCC. PRCC and MTSC have significant histologic and histochemical overlap including elongated tubules and stromal Alcian blue positive mucin deposits. Methods/Case Report We report a case of a 75 year old female who underwent a robotic assisted partial nephrectomy for resection of a 5.7 x 5.2 x 5.0 cm left upper pole solid renal mass. Spindle cell change with elongated tubules reminiscent of MTSC was present in several blocks; however, the luminal surface was shaggy favoring PRCC. Patchy prominent extracellular Alcian blue positive mucin deposits were also present. PRCC and MTSC both express CK7, AMACR, and EMA. However, absent expression of E-cadherin and strong CD10 expression favored PRCC. Multiple foci of solid spindle cells in a whorled pattern with clear cell change, necrosis, and high grade nuclei bordering on sarcomatoid RCC were present in other blocks. Multiple papillations and psammoma bodies also supported PRCC. A spectrum of spindle cell change was present, ranging from elongated tubules reminiscent of MTSC to whorled foci with high grade nuclei approaching sarcomatoid RCC. Results (if a Case Study enter NA) NA Conclusion Submission of multiple sections and awareness of the protean morphologic features of PRCC are essential in making the correct diagnosis.

MR characteristics of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney: comparison with clear cell and papillary subtypes of renal cell carcinoma.

To describe MR features of mucinous tubular spindle cell carcinoma (MTSCC) of the kidney that may help differentiate from clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC). 15 MTSCCs were retrospectively evaluated by MR with T2-weighted image without fat suppression (n = 15) and dynamic contrast-enhanced(DCE), fat-suppressed T1-weighted GRE (n = 11). Size-matched ccRCC (n = 30) and pRCC (n = 30) were evaluated as control. T2 ratio was calculated as the signal intensity (SI) ratio of the lesion to the renal cortex on T2W images. Enhancement ratio (ER) was calculated as (SIpost - SIpre)/(SIpre), where SIpre (SIpost) is the SI of the entire lesion on each phase of DCE images. Early nodular enhancement was subjectively evaluated in MTSCC. T2 ratio and ER were compared using the Mann-Whitney U test with Bonferroni correction. The mean value of T2 ratio was highest in ccRCC (1.24), followed by MTSCC (1.02), and pRCC (0.84). Difference of T2 ratio was significant between ccRCC and pRCC (p < 0.001), but not between MTSCC and ccRCC (p = 0.4) or between MTSCC and pRCC (p = 0.2). The mean ER of MTSCC, ccRCC and pRCC were 1.33, 1.53 and 0.38 in corticomedullary phase (CMP), 1.60, 1.61 and 0.69 in nephrographic phase (NGP) and 1.79, 1.35 and 0.77 in excretory phase (EP), respectively. ERs were significantly different between MTSCC and pRCC in CMP (p = 0.01), NGP (p = 0.003), and EP (p = 0.002). Early nodular enhancement was observed in 4/11 MTSCC (36%), 17/30 ccRCC (57%), and 2/30 pRCC (7%). MTSCC has distinct MR features that can help differentiate from ccRCC and pRCC. MTSCC enhances more avidly compared to pRCC and shows gradual progressive enhancement.

Renal mucinous tubular and spindle cell carcinoma: clinicopathological and whole exome sequencing analyses

Objective: To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of renal mucinous tubular and spindle cell carcinoma (MTSCC), and to explore the all-exon mutations, microsatellite stability and tumor mutational burden (TMB) in MTSCC cases. Methods: The data of 5 patients with MTSCC that were submitted to the Department of Pathology, First Affiliated Hospital of Soochow University, China from January 2008 to May 2020, were reviewed and analyzed. The whole exome sequencing (WES) was conducted in all patients, while 3 of them were subject to the analyses of microsatellite stability and TMB. Results: Among the 5 patients, 3 were males and 2 were females. They were 37-76 years old. The maximum diameter of the tumor was 3.5-6.0 cm. The borders of the tumors were well defined. Microscopically, MTSCC was characterized by tubular structure, spindle cell and mucinous stroma, and the nuclear grade of tumor cells was overall low. The average follow-up was 15 months, and no recurrence or metastasis was found. Immunohistochemistry showed that all 5 cases were positive for broad-spectrum cytokeratin (CKpan), cytokeratin (CK)7, CK19, vimentin, PAX8, and P504s (varying expression levels), and the Ki-67 positive index was low. The WES of 5 cases showed that NF2 and PTPN14 exhibited higher mutation rates, which were 3/5 and 2/5, respectively. The microsatellite stability analysis indicated that the 3 cases were all microsatellite stable, and the TMB analysis showed that the TMB of the 3 cases were all <9 mut/Mb. Conclusions: MTSCC is a unique, low-grade pleomorphic kidney tumor. The WES analyses suggest that NF2 and PTPN14 have a higher mutation rate, indicating that the occurrence and development of MTSCC may be closely related to the Hippo pathway. The analysis of microsatellite stability indicates that there is no significant relationship between microsatellite stability and MTSCC, and the TMB analysis suggests that MTSCC patients may not benefit from immunotherapy.

Renal Mucinous Tubular and Spindle Cell Carcinoma;Case Report

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is an uncommon recently recognized renal cell carcinoma. We reported A 60 year's old man who presented with right flank pain, abdominal swelling and one attack of hematuria. The intraoperative finding was a huge cystic swelling arising from the right kidney occupying almost all the abdominal cavity displacing the bowel to the left side of the abdomen. There was no ascites or evidences of metastasis. Right radical nephrectomy was done . Then the diagnosis of renal MTSCC was established. General condition of the patient was improved and one year prognosis was satisfactory. This is the first reported case of MTSCC in Sudan, and the outcome of treatment was satisfactory .

26. Chromosomal characterization of six new cases of Mucinous tubular and spindle cell carcinoma of the kidney

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma (RCC), recognized as a distinct entity in the 2004 World Health Organization (WHO) tumor classification. It has indolent clinical behavior and characteristic histological features with an admixture of low-grade elongated tubules and bland spindle cells in a mucinous or myxoid stroma. Genetic studies of MTSCC are limited with only 5 reported cases of karyotype analysis, less than 80 cases for chromosome copy number analysis and 15 with next generation sequencing studies.

New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

Collision Tumor Composed of Renal Oncocytoma and Mucinous Tubular and Spindle Cell Carcinoma: Not a Rare Occurrence

Abstract Primary renal collision tumors have been rarely reported in the literature. Our institution reported the first case of a renal collision tumor that comprised oncocytoma and mucinous tubular and spindle cell carcinoma (MTSCC). In this study, upon review of this index case and a second case encountered in our practice, we performed molecular characterization of each component using next-generation sequencing, which did not detect any somatic mutations. In addition, we reviewed resection cases of oncocytomas for previously undetected MTSCC components. While no additional definitive oncocytoma-MTSCC collision tumor cases were identified, 2 cases with entrapped tubules within the central scar of the oncocytoma that possessed some features of MTSCC were encountered, raising the differential diagnosis of oncocytoma-MTSCC collision tumors versus entrapped renal tubules. We propose the following histomorphologic criteria to distinguish a true MTSCC component: (1) expansile mass lesion greater than 0.5 cm; (2) dense proliferation of tubules lined by plump cells; and (3) background of loose myxoid collagenous stroma. In contrast, entrapped tubules tend to form a smaller, stellate-shaped area with atrophic tubules within a dense collagenous stroma. Nevertheless, the occurrence of the 2 described cases provides evidence that the incidence of this collision tumor may not be extremely rare. Therefore, we recommend careful examination and generous sampling of oncocytomas, particularly from the central scarred region or in cases exhibiting atypical gross appearance. Further studies with additional cases are required to better document the relationship and molecular pathogenesis of MTSCC from the central scars of oncocytomas.

IPSILATERAL SYNCHRONOUS MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA AND CLEAR CELL PAPILLARY RENAL CELL CARCINOMA: A CASE REPORT AND REVIEW OF THE LITERATURE

Renal cell carcinoma (RCC), the most common solid lesion of the kidney, accounts for approximately 2%-3% of all malignancies among adults. Clear cell carcinoma and papillary cell carcinoma are the most common types of renal tumors. Some case reports have described synchronous benign and malignant tumors in the same kidney. In particular, angiomyolipoma and RCC in patients with tuberous sclerosis (TSC) and non-TSC have been reported many times in the literature. However, unilateral concordance of malignant renal tumors is very rare; thus, only few cases have been reported in the literature.Here we report the case of a 58-year-old male who had ipsilateral synchronous mucinous tubular and spindle cell carcinoma (MTSCC) and clear cell papillary renal cell carcinoma (CCPRCC). Both cancers are rare and relatively recently defined subtypes of RCC. Additionally, both were successfully treated using partial nephrectomy. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. The classic type of MTSCC is characterized by small elongated tubules lined with clear cuboidal or spindle cells with mucinous stroma. Neoplastic cells always exhibit low-grade histological features. However, unclassified variants of MTSCC, such as mucin-poor, papillary, high-grade, and sarcomatoid variants, have also been reported. MTSCC is considered to have a relatively good prognosis, but some patients with poor prognoses have recently been reported. CCPRCC is a recently recognized entity and represents the fourth most common variant of RCC. It has unique morphological and immunohistochemical features and shows indolent clinical behavior. Microscopically, CCPRCC may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC, with clear cell changes. In 2006, CCPRCC was described as a subtype of renal tumors in patients with end-stage renal disease. However, currently, CCPRCC has also been shown to occur in kidneys with normal function.To the best of our knowledge, this is the first report of ipsilateral synchronous MTSCC and CCPRCC, which we present with a review of the pertinent literature.

Mucinous tubular and spindle cell carcinoma of the kidney: Five case reports and review of the literature.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.

Adverse histology, homozygous loss of CDKN2A/B, and complex genomic alterations in locally advanced/metastatic renal mucinous tubular and spindle cell carcinoma.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma with characteristic histologic features and chromosomal alterations. Although typically indolent, a small subset of cases has been reported to exhibit aggressive clinical behavior. We retrospectively identified 33 patients with MTSCC, consisting of 10 cases of locally advanced / metastatic-MTSCC (pT3 or N1 or M1) and 23 kidney confined-MTSCC (pT1/T2) without disease recurrence or progression. Utilizing a single nucleotide polymorphism array and a targeted next-generation sequencing platform, we examined genome-wide molecular alterations in 24 cases, including 11 available samples from 8 patients with locally advanced / metastatic-MTSCC. Ten patients with locally advanced / metastatic-MTSCC were 8 females (80%) and 2 males (20%). At nephrectomy, 7 of these 10 cases (70%) were pT3 or pN1 while the remaining 3 (30%) were pT1/T2. Eight patients (80%) developed metastases and common sites included lymph node (4, 40%), bone (4, 40%), and retroperitoneum (3, 30%). Four patients died of disease (40%) during follow-up. Locally advanced / metastatic-MTSCCs shared typical MTSCC genomic profiles with loss of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while some exhibited additional complex genomic alterations, most frequently a relative gain of 1q (7/8). Homozygous loss of CDKN2A/B was observed in 3 (38%) locally advanced / metastatic-MTSCCs. Tumor necrosis, solid nested/sheet pattern, irregular trabecular/single-file infiltration in a desmoplastic stroma, lymphovascular space invasion, and increased mitotic activity were associated with locally advanced / metastatic-MTSCCs (all p < 0.05). Our findings reveal that MTSCCs with aggressive clinical behavior have progressed through clonal evolution; CDKN2A/B deletion and additional complex genomic abnormalities may contribute to this process. Recognizing the morphologic presentation of high grade MTSCC and evaluating adverse histologic features seen in these tumors can help establish a definitive diagnosis and stratify patients for treatment and prognostication.

Difficulty in differential diagnosis for renal cancer with microscopic papillary architecture: overlapped pathological features among papillary renal cell carcinoma (RCC), mutinous tubular and spindle cell carcinoma, and unclassified RCC. Lessons from a Japanese multicenter study.

In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3years. Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.

Cytological and Ultrastructural Findings of Mucinous Tubular and Spindle Cell Carcinoma: A Case Report

The 2016 World Health Organization Classification of Tumors recognized mucinous tubular and spindle cell carcinoma (MTSCC) as a rare histological variant of renal cell carcinoma (RCC). To date, a limited number of studies have reported this tumor concerning histology, and only a handful of those have reported cytological and ultrastructural features. This study aims to report a case of MTSCC in a female patient in her early 50s who presented with a chief complaint of gross hematuria, and to discuss relevant cytological and ultrastructural findings. Imaging revealed a 30 mm tumor in the left kidney, suggesting the presence of RCC, and left nephrectomy was performed. In addition, scratched cytology of tumor surface revealed clusters of tumor cells with clear cell boundaries extending two-dimensionally in papillary or dendritic arrangements with interspersed blood vessels and stromal components that were stained light green. Histologically, the tumor was composed of small and uniform cells arranged in elongated tubular architectures and spindle fascicles with occasional papillary structures; the stroma was acidophilic and contained colloidal substances that tested positive for Alcian blue and periodic acid-Schiff stain. Concordant with immunohistochemical results, the tumor was diagnosed with MTSCC. Furthermore, transmission electron microscopy revealed tubular structures with microvilli, abundance of mitochondria in the cytoplasm, cellular interdigitations and widened interstitium.

Synchronous Mucinous Tubular and Spindle Cell Carcinoma of the Kidney and Papillary Carcinoma of the Thyroid

A 55 year old female, presented with flank pain and fullness since 2 years. On examination, a 10x10cm, ballotable lump was present in the right flank. CT Abdomen showed a 9.5x8.8 cm, exophytic mass lesion in the right kidney with patchy arterial enhancement and heterogenous enhancement in the venous phase. Whole body PET CT showed well defined, metabolically active masses in the right kidney, thyroid and cervical lymph nodes. Nephrectomy specimen received, showed a tumor measuring 12x7x6.5 cm creamy-white, fleshy, replacing the kidney. Histopathology revealed an unusual renal neoplasm with tubule formation merging with bland spindle cells and a focal myxoid stroma. Tumor cells were immunoreactive for CK7, EMA, vimentin and were negative for PAX8, CD10 & AMACR. The diagnosis of Mucinous Tubular and Spindle cell carcinoma (MTSCC) was established. FNAC of the thyroid nodules showed a classic papillary thyroid carcinoma.

Mucinous tubular and spindle cell carcinoma of kidney: A case report of a mucin and stroma poor tumour causing diagnostic difficulty

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and unusual variant of renal cell carcinoma (RCC). We report an unusual tumour in an 81-year-old male with an incidental finding of a tumour in the lower pole of the left kidney. The core biopsy showed a renal cell carcinoma with mostly tubular morphology and an immunophenotype indistinguishable from papillary renal cell carcinoma. The partial nephrectomy showed a tumour comprising predominantly tubular structures with focal abortive papillae, psammomatous calcifications and scattered small aggregates of foam cells. Only focal areas showed myxoid change and spindle cells, but this made the diagnosis of a mucinous tubular and spindle cell carcinoma more straightforward. This case highlights the importance of recognising a mucin/stroma poor variant of MTSCC of the kidney and how the entity can cause diagnostic confusion with papillary renal cell carcinoma as there is morphologic and immunophenotypic overlap, particularly on core biopsy.

Bilateral renal mucinous tubular and spindle cell carcinoma (MTSCC) – an extremely rare occurrence in children

Bilateral renal mucinous tubular and spindle cell carcinoma (MTSCC) – an extremely rare occurrence in children