Mucinous Tubular and Spindle Cell Carcinoma of the Kidney: A Rare Renal Neoplasm-Case Report and Literature Review.

Mucinous tubular and spindle cell carcinoma with papillae: A report of 5 cases and comparison with 18 cases of papillary renal cell carcinoma.

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.

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 and its prognostic paradox: A population-based study.

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.

To explore the feasibility of CT and MRI in differentiating mucinous tubular and spindle cell carcinoma (MTSCC) and papillary renal cell carcinoma (PRCC). 23 patients with MTSCC and 38 patients with PRCC were studied retrospectively. CT and MRI were undertaken to investigate differences in tumour characteristics. 23 patients with MTSCC and 38 patients with PRCC (included 15 cases Type 1,and 23 cases Type 2), tumours (mean diameter 3.7 ± 1.6 cm vs 4.6 ± 1.7 cm, p < 0.05), cystic components (5 vs 32, p < 0.01), calcifications (3 vs 11, p > 0.05), haemorrhage (1 vs 22, p < 0.01), tumour boundaries (1 vs 37, p < 0.01), and homogeneous enhancement (20 vs 11, p < 0.01). The density of MTSCC was lower than that of PRCC, normal renal cortex (p < 0.05), except for the medulla(p > 0.05). MTSCC and PRCC tumour enhancement were lower than that for normal cortex and medulla during all enhanced phases (p < 0.05). Enhancement was higher with PRCC than with MTSCC tumours during all phases (p < 0.05). On MRI, nine cases of MTSCC and 19 cases of PRCC, tumour showed homogeneous (9 vs 3, p < 0.01), heterogeneous (0 vs 16, p < 0.01), hyperintense on T1WI (0 vs 15, p < 0.01), slightly hyperintense on T2WI (9 vs 1, p < 0.01), hypointense on T2WI (0 vs 15, p < 0.05) , relatively high signal intensity was seen on DWI (9 vs 15, p > 0.05), respectively. CT imaging features of MTSCC include isodense or hypodense mass on unenhanced CT, with unclear boundaries; however, PRCC showed mild hyperdensity, easily have cystic components. The degree enhancement of MTSCC is lower than that for PRCC. On MR, MTSCC was slightly hyperintense on T2WI, whereas PRCC was hypointense. 1.CT imaging features of MTSCC include isodense or hypodense mass on unenhanced CT, with unclear boundaries.2. CT imaging features of PRCC include mild hyperdensity on unenhanced CT, easily have cystic components.3. On enhanced CT, the degree enhancement of MTSCC is lower than that for PRCC. On MR, MTSCC was slightly hyperintense on T2WI whereas PRCC was heterogeneously hypointense on T2WI.

INTRODUCTION: Collecting duct carcinoma (CDC) is an extremely rare type of renal epithelial tumor that arises from the distal convoluted tubule of kidney. Prognosis of CDC is poor due to its rapid growth and widespread metastasis. It is often difficult to distinguish CDC from pelvic urothelial carcinoma and high grade papillary Renal Cell Carcinoma. Mucinous tubular and spindle cell carcinoma (MTSCC) of kidney is also a rare but low grade epithelial neoplasm. It is often misdiagnosed as sarcomatoid renal cell carcinoma, papillary renal cell carcinoma or other aggressive renal neoplasms. MATERIALS AND METHODS: This is a study of two extremely rare cases of kidney tumors conducted in a tertiary care hospital. We studied clinical presentation, location within the kidney, radiological findings, histopathological findings, immunohistochemical findings and treatment provided. CASE REPORT: A case of CDC involving the renal medulla extending up to the cortex of upper pole of right kidney and another case of MTSCC involving the middle and upper part of left kidney have been studied. Patient with CDC was a 71 year old male presented with gross hematuria, backpain, fatigue and weight loss. MTSCC was incidentally detected in a 62 year old female. Histopathological examination of the formalin fixed paraffin embedded tissue sections were done for the diagnosis of these two rare entities. Immunohistochemistry was done for exclusion of other diagnostic entities. CONCLUSION: CDC is a rare aggressive renal neoplasm which is commonly associated with nodal and distant metastasis at the time of presentation. Early diagnosis of this tumor is essential to improve the survival of the patients. Immunohistochemical analysis helps to differentiate CDC from other renal cell carcinoma (RCC) subtypes. MTSCC is a low grade hypovascular renal tumor. The diagnosis of MTSCC fundamentally depends on histopathological examination (HPE) findings. Surgical resection of the tumor is essential for long term survival. Keywords: Collecting duct carcinoma, hematuria, histopathological examination, immunohistochemistry, laparoscopic nephrectomy, renal cell carcinoma.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare type of renal cell carcinoma that frequently exhibits histologic and immunophenotypic features overlapping with type 1 papillary renal cell carcinoma (PRCC). To clarify molecular attributes that can be used for this difficult differential diagnosis, we sought to delineate the genome-wide copy number alterations in tumors displaying classic histologic features of MTSCC in comparison to the solid variant of type 1 PRCC and indeterminate cases with overlapping histologic features. The study included 11 histologically typical MTSCC, 9 tumors with overlapping features between MTSCC and PRCC, and 6 cases of solid variant of type 1 PRCC. DNA samples extracted from macrodissected or microdissected tumor areas were analyzed for genome-wide copy number alterations using an SNP-array platform suitable for clinical archival material. All cases in the MTSCC group exhibited multiple chromosomal losses, most frequently involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while lacking trisomy 7 or 17. In contrast, cases with overlapping morphologic features of MTSCC and PRCC predominantly showed multiple chromosomal gains, most frequently involving chromosomes 7, 16, 17, and 20, similar to the chromosomal alteration pattern that was seen in the solid variant of type 1 PRCC cases. Morphologic comparison of these molecularly characterized tumors identified histologic features that help to distinguish MTSCC from PRCC, but immunohistochemical profiles of these tumors remained overlapping, including a marker for Hippo-Yes-associated protein signaling. Characteristic patterns of genome-wide copy number alterations strongly support MTSCC and PRCC as distinct entities despite their immunohistochemical and certain morphologic overlap, and help define histologic features useful for the classification of questionable cases.

Our recent study revealed recurrent chromosomal losses and somatic mutations of genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and the Knepper data set of microdissected rat nephrons. We identified VSTM2A and IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then assessed their expression by RNA in situ hybridization (ISH) in 113 tumors, including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2 unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and specificity were calculated as the area under the receiver operating characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA sequencing strongly correlated with VSTM2A ISH score (r(2)=0.81, P=0.00016). The majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A. IRX5, nominated as a lineage-specific biomarker, showed moderate to high expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by RNA sequencing strongly correlated with IRX5 ISH score (r(2)=0.69, P=0.00291). VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC: 87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors with overlapping histology. Furthermore, our results suggest MTSCC displays an overlapping phenotypic expression pattern with the loop of Henle region of normal nephrons.

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

The solid variant of papillary renal cell carcinoma (PRCC) is distinguishable genetically from mucinous tubular and spindle cell carcinoma (MTSC) of the kidney by the presence of trisomy for chromosomes 7 and 17; however, at the morphologic and immunohistochemical levels, these neoplasms overlap significantly. The key morphologic feature distinguishing these two is thought to be the low grade of the spindle cell areas of MTSC; spindle cell areas in PRCC generally signify sarcomatoid change and are high grade. We report 5 cases of PRCC with low-grade spindle cell foci, closely mimicking MTSC. All patients were male, and ranged in age from 17 to 68 years. All tumors were predominantly solid, featuring compact areas of low-grade spindle cells lining thin, angulated tubules. Mucinous stroma was not appreciated in any case. All cases were diffusely immunoreactive for cytokeratin 7, and focally CD10 positive. All 5 cases showed trisomy of chromosome 7, and 3 of 5 showed trisomy of chromosome 17 by fluorescence in situ hybridization, supporting classification as PRCC. These cases further reported morphologic overlap between MTSC and PRCC. Before a diagnosis of metastatic MTSC or MTSC with unusual morphology is rendered, the possibility of PRCC with low-grade spindle cell foci should be considered. Fluorescence in situ hybridization analysis effectively separates these morphologically very similar yet genetically distinctive entities.

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 (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.

To investigate the clinical and pathological features of the mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. Seven cases of MTSCC were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD10, CK7, CK18, CK19, Villin, EMA, P504S and vimentin. The literature on this tumor was reviewed to discuss the histological features of MTSCC and its clinical behavior. Three of 7 cases were male and the other 4 were female. The mean age of the patients was 48.2 years old, with a range from 39 to 61 years. All the patients presented no symptom and their tumors were found by health examination. Tumors averaged 5.5 cm in greatest dimension (range from 4.0 cm to 9.0 cm). The tumors were well-circumscribed without capsules, and the cut surfaces were solid and soft with white-tan color. By light microscopy, tumors were composed of tightly packed, small, elongated tubules with transitions to spindle cell components. Five cases had mucinous stroma. Clear cell clusters, focal sarcomatoid differentiation, papillations and foamy macrophages were seen in several cases. Immunohistochemically, all 7 cases showed positive for CK7, five of 5 cases positive for EMA, CK18 and P504S, four of 5 cases positive for CK19, but heterogeneous for CD10, villin and vimentin expression. No evidence of local recurrence or distant metastases was identified in the 5 patients with follow-up information. The mucinous tubular and spindle cell carcinoma is a low-grade and polymorphic neoplasm. The morphology of these tumors may not be uniform with a wide histological spectrum. The tumors can be tubular predominant or spindle cells predominant with scant to abundant mucinous stroma, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, necrosis and sarcomatoid differentiation. Immunohistochemically, MTSCC can express the markers from the proximal convoluted tubules to collecting tubules.

Background: Mucinous tubular and spindle cell carcinoma (MTSC) is a rare and newly described type of renal cell carcinoma (RCC) with relatively indolent behavior. Although there are small series of this clinical entity in the literature, its histogenetic origin or line of differentiation remains unclear. Patients and Methods: A 67-year-old woman was hospitalized for flank pain; imaging studies revealed a 6.5-cm mass in the right kidney. She was referred for fine needle aspiration of the lesion, which showed an epithelial tumor with round to oval nuclei associated with strands of metachromatic stromal tissue. Cytopathologic diagnosis was consistent with RCC. Results: Subsequent right heminephrectomy was performed and the surgical pathology specimen showed an MTSC of the kidney. The patient has done well postoperatively, with 24 months of benign follow-up. Conclusion: A precise differential diagnosis between MTSC and other renal carcinomas (e.g. papillary RCC with sarcomatoid transformation) is important for predicting patient prognosis. Even though MTSC is a rare cause of renal masses, it should be included in the differential diagnosis, especially because its imaging might be misleading, mimicking other benign renal diseases. Heminephrectomy is the preferred treatment in these subjects.