Background

There are various types of renal cell carcinomas with distinct underlying molecular features, unique immunophenotypes, varying degrees of clinical outcomes, and therapeutic implications. Originally, mucinous tubular and spindle cell carcinoma (MTSCC) was described as an unclassifiable tumor in 1998 (Lima et al. 2013). In 2004, it was described as a distinct entity (Yang et al. 2010). It is more commonly reported in females and the mean age at presentation is 53 years (Ferlicot et al. 2005). Although MTSCC itself has low malignant potential, rare cases with sarcomatoid change have been reported with aggressive behavior. The MTSCC is composed of spindle cells admixed with tubules lined by bland cuboidal cells set in a background of a variable amount of myxoid stroma (Ellis and Flower 2004).

We present a case of a 23-year-old male who reported bilateral flank pain. A left renal mass was detected on computerized tomography (CT) scan followed by a histopathological diagnosis of MTSCC with 70% tumor showing the sarcomatoid change.

Case presentation

A 23-year-old male reported to the urology department with chief complaints of bilateral flank pain and fever from the last fifteen days associated with a history of weight loss. There was no history of hematuria. He was a non-smoker and had no history of tuberculosis, diabetes mellitus, hypertension, asthma, or ischemic heart disease. There is no family history of any kind of malignancy. On physical examination, the patient was vitally stable with unremarkable general and systemic examination.

All the hematological investigations including renal function tests were within normal limits. CT scan chest showed tiny pulmonary nodules suspicious to be metastatic. CT scan (Fig. 1) abdomen showed well-defined heterogeneously relatively hypo-enhancing, ball-shaped, left renal mass with loss of fat interface with adjacent large bowel, compressing and displacing pelvicalyceal system with no definite vascular extension. A large hypodense lesion in segment VI of the liver and additional smaller hypodense lesions in the right lobe were also noted. Multiple enlarged upper abdominal and left renal hilar lymph nodes were seen.

In wake of complete clinical, laboratory, and radiological assessment left radical nephrectomy and adrenalectomy with lymph node dissection was performed.

On gross examination, a 10.5 × 9.0 × 6.0 cm well-circumscribed tumor mass was found at the lower pole with necrosis on the cut surface. The tumor was limited to the renal parenchyma, away from sinus fat. Histological analysis revealed a tumor comprised of tubular structures set in a mucinous background. The tubules were lined by cuboidal cells having highly pleomorphic nuclei. At places, the cuboidal cells merged with spindle cell areas. Almost 70% of the tumor showed sarcomatoid differentiation and tumor necrosis was also present. The sarcomatoid cells were pleomorphic with hyperchromatic nuclei and prominent nucleoli as in Fig. 2. Abundant mitotic figures were also present. The tumor was found to be focally invading into the perinephric fat, beyond the renal capsule. Carcinoma was found positive in 09 out of 13 periaortic lymph nodes.

On immunohistochemistry, cytokeratin 7 (CK7) and alpha-methyl co-A racemase (AMACR) were positive, paired-box gene 8 (PAX-8) and carbonic anhydrase IX (CA-IX) were focal positive, CD10 was focal weak positive while TFE3 was negative in the tumor as illustrated in Fig. 3. According to these morphological and immunohistochemical findings, a diagnosis of high-grade MTSCC was made.

The postoperative course of the patient was uneventful and was discharged on day 3 in a stable condition. On sixth month follow-up, the patient was in good health.

Fig. 1
figure 1

CT Scan Abdomen showing left renal mass

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Discussion

MTSCC is a rare neoplasm, mostly following an indolent course, but some cases of MTSCC have been reported showing sarcomatoid change (Dhillon et al. 2009; Pillay et al. 2008; Simon et al. 2008; Isono et al. 2020; Arafah and Zaidi 2013; Sugimoto et al. 2019; Kenney et al. 2015; Gong et al. 2020). The characteristic features of seven cases are compared with our case in Table 1. Sarcomatoid change has been previously more commonly reported in other common types of renal cell carcinoma. Patients with renal cell carcinoma showing sarcomatoid change presented at an advanced stage and followed a bad prognosis (Venturina et al. 2001).

The tumor is prevalent in females with a ratio of 4:1 against males and an age group of 13 to 82 years (Yang et al. 2010; Zhao et al. 2015). MTSCC was previously considered to be originating from the loop of Henle or collecting duct but later immunohistochemical analysis showed it to be CK7 and AMACR positive. This suggested its origin from the proximal segment of the nephron showing its close relation to papillary renal cell carcinoma. Occasionally, the differentiation between both types of carcinomas becomes difficult based on routine histology and immunohistochemistry, necessitating the use of genetic studies for making a proper diagnosis (Shen et al. 2007).

Imaging studies show that the tumor mostly appears well-circumscribed and homogenous with heterogeneous and slow progressive enhancement in the corticomedullary and nephrogenic phase of CT and MRI. It has a high T2 and a low ADC value on MRI. (Cornelis et al. 2017).

On gross examination, the tumor has distinct borders with most of the tumor bulk to be found in the medullary area. Morphological analysis shows that the tumor is composed of elongated branching tubules and cords admixed with spindle cell areas. The tubular structures are lined by cuboidal cells containing scant eosinophilic cytoplasm and low-grade nuclei. Mucinous stroma is almost always present in all cases. Sometimes papillary structures, foamy macrophages, sarcomatoid change, and necrosis can be identified in tumors. The sarcomatoid cells have a high nuclear to cytoplasmic ratio, pleomorphic hyperchromatic nuclei, and prominent nucleoli (Ro et al. 1983).

Fig. 2
figure 2

A Spindle cell proliferation against myxoid stroma (B) with areas containing cords or tubules of cuboidal cells (H&E X10M), (C) foci showing higher nuclear grade and (D) sarcomatoid change (H&E X 20 M)

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Fig. 3
figure 3

A CK7 (X10M), (B) AMACR (X20M), (C) CD10 (X10M) and (D) lymph node showing metastatic carcinoma (H&E X20M)

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In our case, the sarcomatoid change was present constituting 70% of the tumor. In addition, 40% of the tumor was showing necrotic areas. This upgraded the tumor to ISUP grade four which shows its deviation from commonly reported cases of a low-grade type of MTSCC.

Immunohistochemically, the tumor usually shows positivity for CK7, AMACR, renal cell carcinoma (RCC) antigen, and Lewis X (CD15) in both tubular and mucinous areas. CD 10 is negative most of the time however in some cases it may be positive (Sternberg et al. 2010).

Table 1 Characteristics of MTSCC cases with sarcomatoid change (Dhillon et al. 2009; Pillay et al. 2008; Simon et al. 2008; Isono et al. 2020; Arafah and Zaidi 2013; Sugimoto et al. 2019; Kenney et al. 2015; Gong et al. 2020)
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Genetic studies have shown various chromosomal abnormalities including losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, 22 and X (Rakozy et al. 2002) and gains of chromosomes involving 2, 4, 5, 7, 9, 10, 12, 16, 17, 18, 19, 20, 22 and X (Dhillon et al. 2009; Brandal et al. 2006). Recently genetic study of MTSCC using array comparative genomic hybridization showed losses involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, 22 without any gains in chromosomes, in low and high-grade MTSCC of classical type, while the tumors having histopathological features overlapping with papillary RCC showed a variable pattern of losses and gains in chromosomes, including gains involving chromosomes 7 and 17 in 2 out of 4 analyzable tumors (Peckova et al. 2015). However, FISH based studies show that MTSCC does not show gains of chromosomes 7 and 17 (Cossu-Rocca et al. 2006). This emerging evidence has proved that although morphological and immunohistochemical features overlap with those of papillary RCC, genetically it is a separate entity.

There are no definite guidelines for the treatment of MTSCC, however surgical excision remains adequate for localized cases. For metastatic tumors, improvement in patient survival and reduced tumor burden have been achieved in some cases by benefiting from the use of sunitinib, a tyrosine kinase inhibitor (Volpe et al. 2011). In a recent case report, combined immunotherapy with ipilimumab and nivolumab showed complete recession of the metastatic MTSCC (Fuchizawa et al. 2021). In a study (Lebacle et al. 2019), renal cell carcinomas with sarcomatoid change showed better expression of PD-1/PD-L1 as compared to conventional carcinomas. So, sarcomatoid RCC will respond better to targeted immunotherapy. However, further studies are required for setting proper management plan for metastatic MTSCC.

Conclusions

MTSCC is a rare tumor. This case report presents rare renal carcinoma subtype with sarcomatoid change. The sarcomatoid change is associated with aggressive behavior which is why the identification of this high-grade feature is essential. Complete morphology, immunohistochemistry and cytogenetics are required for definite diagnosis of this tumor. Close follow-up of tumor is required for understanding of complete biological behavior of this tumor.