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  Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 57  |  Issue : 3  |  Page : 267-281
 

Mucinous tubular and spindle cell carcinoma of the kidney: A case series with a brief review of the literature


1 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Uro-oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Department of Radiology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Submission30-Sep-2018
Date of Decision25-Oct-2018
Date of Acceptance26-Nov-2018
Date of Web Publication08-Jul-2020

Correspondence Address:
Santosh Menon
Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_642_18

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 » Abstract 


Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare low grade renal tumour exhibiting characteristic morphological features. We share our experience and discuss briefly, a review of the current literature.
Methods: Electronic medical records were searched between January 2005 to January 2017. The histopathology and immunohistochemistry slides were retrieved and reviewed.
Results: Eleven cases of MTSCC were identified. Mean age at presentation was 53.9 (age range 41 to 71) years with a slight female preponderance (F: M=6:5). Clinical stage at presentation was: Stage I (4 cases), Stage II (3 cases), Stage III (1 case), and Stage IV (3 cases). The average tumour size was 7.5cm (range 3.5 to 17cm). Microscopically, characteristic biphasic tumour with tubular and spindle cell morphology with variable mucinous stroma was noted in all. The prominent immunohistochemical profile revealed positivity for CK7 (7/8, 87.5%), AMACR (6/8, 75%), AE1/3 (4/4, 100%), CD10 (3/10, 27.3%), and Vimentin (3/3, 100%). Seven patients (Stage I and II) had been treated with nephrectomy, whereas only a diagnostic biopsy was available in four patients who presented with locally advanced disease (n=1) or distant metastasis (n=3) at presentation. The mean follow-up was 37.8 months (range 8 to 96 months), available in 10 out of 11 patients, without recurrence in nine while one died 8 months after diagnosis.
Conclusion: MTSCC is an indolent renal cancer with characteristic morphology. However, presentation with locally advanced disease or distant metastasis may be seen in a subset of these patients. This warrants close follow-up in even localized tumors.


Keywords: Mucinous, tubular, renal cell carcinoma, spindle


How to cite this article:
Adamane SA, Menon S, Prakash G, Bakshi G, Joshi A, Popat P, Desai SB. Mucinous tubular and spindle cell carcinoma of the kidney: A case series with a brief review of the literature. Indian J Cancer 2020;57:267-81

How to cite this URL:
Adamane SA, Menon S, Prakash G, Bakshi G, Joshi A, Popat P, Desai SB. Mucinous tubular and spindle cell carcinoma of the kidney: A case series with a brief review of the literature. Indian J Cancer [serial online] 2020 [cited 2020 Oct 1];57:267-81. Available from: http://www.indianjcancer.com/text.asp?2020/57/3/267/289211





 » Introduction Top


Renal cell carcinoma (RCC) encompasses a family of malignant epithelial tumors arising from the renal tubular epithelium with diverse morphologic features. Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of RCC. MTSCC is recognized and included in World Health Organization (WHO) 2004 as a distinct entity with characteristic histological appearance, delineating it from other subtypes of RCC.[1-6] Except for a distinct female preponderance, the clinical presentation and radiology are no different from other common renal cancers. Hence, histopathology forms the basis of diagnosis and further management. MTSCC is a low-grade renal tumor of uncertain histogenesis and indolent clinical behavior. However, rare reports of recurrences, metastasis to lymph nodes, bones, liver, and lungs; [4,7-11] and sarcomatoid transformation have been documented.[8],[10],[12],[13],[14] We hereby describe the largest series of MTSCC from India with their clinical, histological and immunohistochemical profile and clinical follow-up. A brief review of current literature is also discussed.


 » Methods Top


The electronic medical record (EMR) and surgical pathology database of our institution were searched with keywords 'mucinous,' 'tubular,' 'spindle,' and 'renal cell carcinoma' from January 2005 to January 2017. The histology and immunohistochemistry (IHC) of the archived slides were reviewed by three pathologists (SAA, SM, and SBD). The clinicoradiological details and treatment details were obtained from EMR.


 » Results Top


Eleven pathologically proven cases of MTSCC of the kidney were identified over this study period. A total of 2,070 RCC were diagnosed during this study period, and MTSCC constituted 0.53% of the RCC cases. The details of these cases are described below.

Clinical presentation

There were six women and five men in this study with a mean age of 53.9 years (age range = 41–71 years). The most common presenting symptoms were backache (n = 6, 54.5%) and abdominal pain (n = 6, 54.5%). In addition, clinical presentation included hematuria (n = 1, 9.1%), dragging sensation in abdomen (n = 1, 9.1%), and shoulder pain with significant weight loss (n = 1, 9.1%). The clinicopathological data have been summarized in the [Table 1].
Table 1: Clinicopathological features of MTSCC


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Investigations and treatment

Radiological investigation (either computed tomography [CT], sonography, and/or magnetic resonance imaging [MRI] scan) was available in 10 patients. Nine cases had imaging features of RCC and one had angiomyolipoma as a differential diagnosis on CT scan. Surgical intervention was performed with a curative intent in seven patients, which included radical nephrectomy (n = 5) and nephron-sparing surgery (n = 2). In four of the 11 patients, clinicoradiologically, the disease was advanced and hence a diagnosis of MTSCC was rendered on ultrasonography (USG)-guided renal biopsy. These four patients were managed with either radiotherapy to local site (n = 3) or targeted therapy with tyrosine kinase inhibitors (n = 1).

Interestingly, two of our patients had other associated significant medical conditions. One of our patients had synchronous carcinoma of gall bladder for which he had undergone radical cholecystectomy followed by adjuvant chemotherapy. However, the renal mass was addressed with surgical excision alone. Another patient had a coexistent small intracranial meningioma, which was asymptomatic and hence was kept on regular follow-up.

Histopathological features

Gross tumor findings were available in six patients. The average tumor size, as measured grossly in resected specimen or radiologically in inoperable patients, was 7.5 cm (range = 3.5–17 cm). In all the 11 cases, light microscopy revealed a characteristic biphasic tumor comprising of variable proportions of tubular and spindle cell areas [Figure 1]a. Mucinous and/or myxoid change [Figure 1]b was noted in the tumor stroma of all cases, albeit in varying proportions in each case. The tubular component was lined by cuboidal epithelium with pale eosinophilic cytoplasm [Figure 1]c. The spindle cell component [Figure 1]d was arranged in short fascicles and imperceptibly merged with tubular component. One of the cases had abundant histiocytes amongst the spindle tumor cells [Figure 1]e. The nuclei in both the tubular and spindle cell components were low grade and centrally located [Figure 1]f and [Figure 1]g. In a few cases, small to medium-sized nucleoli were also observed. None of the tumors revealed high nuclear grade or anaplasia. Mitotic activity was sparse and was seen in both tubular or spindle cell component. Patchy areas of necrosis and foamy macrophage were also noted in five of our cases, on gross as well as microscopy. Interestingly, one of our cases also revealed focus of coexistent papillary RCC, type 1, which was seen blending with the other components of the tumor. All the four biopsy-diagnosed MTSCC cases, microscopically had well-recognizable tubular and spindle cell components with myxoid stroma. Focal cytoplasmic clearing was noted at places.
Figure 1: Mucinous tubular and spindle cell carcinoma showing biphasic tumor (a) with characteristic mucinous stroma (b) and individual components tubular (c), spindle (d) separately, as well as intermixed. (H and E, ×100). Diffuse histiocytic inflammation was noted in case 11 (e). Distinct low-grade nuclei were noted in both tubular (f) and spindle cell (g) components (H and E ×400)

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IHC had been done in all except one case. In case 2, the diagnosis was solely given on the classic histomorphological features of the tumor without the use of any ancillary IHC technique. Various immunohistochemical antibody markers used in this study are enlisted in [Table 2] and the immunohistochemical profile of a case is shown in [Figure 2] and rest of IHC in this series has been detailed in [Table 3].
Table 2: List of various antibody markers used


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Figure 2: Immunohistochemistry reveals positive staining for CK7, AE1/AE3 (a), AMACR while spindle areas highlighted by SMA (b) (Diaminobenzidine, ×200)

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Table 3: Immunohistochemistry profile of cases


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Follow-up

Follow-up data was available in 10 out of 11 patients in this study. The mean clinical follow-up was 37.8 months (median = 31.5 months; range = 8–96 months). Seven patients were treated surgically with curative intent and did not have recurrence or metastasis till the last follow-up. Three patients had disseminated disease at presentation and were referred for palliative radiotherapy. One patient had a huge tumor (17 cm) and was treated with oral tyrosine kinase therapy. The follow-up data are detailed along with clinicopathological details in [Table 1].


 » Discussion Top


MTSCC is a rare renal tumor with less than 100 cases being described in the literature to date. To the best of our knowledge, this is the largest series of MTSCC from India. MacLennan et al.[15]in 1997 described MTSCC as lower grade spectrum tumor of collecting duct carcinoma. Later, Parwani et al.[1] and Hes et al.[4] reported 4 and 11 cases which they labelled as a low-grade myxoid renal epithelial tumor and cuboidal and spindle carcinoma, respectively. The histogenesis of MTSCC is still a matter of debate with most authors believing either a distal nephron or a collecting duct origin.[3],[16] Another school of thought promotes a loop of Henle origin due to the combined immunophenotype of cytokeratin 7 and racemase expression favoring a proximal nephron origin.[1-4,17-19] With WHO 2004 classification, these neoplasms were recognized as a separate entity along with other low-grade tumors with a favorable prognosis.[6] They have been found in a wide age range (13–82 years) with a female preponderance (M:F = 1:4).[4],[6],[20] In our series, a marginal female preponderance was noted.

The gross size of the tumor has been described varying in size from 1 to 17 cm.[5],[6] However, in current series, the largest tumor size noted was 17 cm (mean = 7.5 cm). This may be due to the delay in seeking medical attention in our group of patients. Microscopically, all our cases had classical tubular and spindle cell components with varying amount of mucinous areas, similar to those described in the literature. One of the cases also revealed admixed papillary RCC areas. Clear cell change in MTSCC,[21] coexistence of conventional RCC,[4],[20] and rarely neuroendocrine differentiation in MTSCC have been described in the literature. [20,22-24] Clear cell change was noted in the biopsy-diagnosed cases; however, clear cell RCC was excluded due to the presence of distinct spindle cell component and absence or focal CD10 expression (1/4). As MTSCC have admixture of tubular, spindle, and mucinous/myxoid areas, preponderance of any single component can lead to a misdiagnosis. A predominant tubular pattern may be wrongly labelled as a type 1 papillary carcinoma with solid growth pattern or as metanephric adenoma. A spindle cell predominant MTSCC is likely to be misdiagnosed as a sarcomatoid RCC or a smooth muscle tumor such as a leiomyomatous-predominant angiomyolipoma. It should be borne in mind that a sarcomatoid RCC will have definite anaplasia unlike the monomorphic spindle cells of MTSCC. However, it is noteworthy that sarcomatoid changes and presence of high-grade nuclei have rarely been described in MTSCC.[12],[13],[24] Needless to emphasize, it is the pathologist's prerogative to take adequate sections from the suspected MTSCC to demonstrate all the different components. The aforementioned differential diagnoses have implications on clinical management and follow-up decisions. Immunohistochemically, MTSCC express markers of both distal (CK7) and proximal tubular (RCC Ma, AMACR, CD15) differentiation. Thus, CK7, EMA, and AMACR are of no value in differentiating MTSCC and papillary RCC.[19],[25] CD10 is expressed in 93% to 100% of papillary RCCs, while only 15% of MTSCC express this marker, thereby serving as a helpful guide in differentiating the two entities. Cossu-Rocca et al.[26] emphasized that gains in chromosomes 7 and 17, and losses of chromosome Y using fluorescence in situ hybridization (FISH) are characteristic genetic events in papillary RCC which can help in differentiating them from MTSCC. In contrast, Zhang et al.[24] found gains of chromosomes 7 and 17 and loss of Y in one of two cases of MTSCC, thereby postulating MTSCC as a subtype of papillary RCC. Comparative genomic hybridization (CGH), FISH, and karyotyping in a few studies have revealed multiple losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, 18, and 22[3],[10],[16],[18],[27] and gains of chromosomes 2, 4, 7, 16, 17, 18, 20, and 22[10],[28],[29] in MTSCC. In this study, the cytogenetic analysis was not performed due to lack of such facilities in routine laboratory practice. Metanephric adenoma is a differential diagnosis and can be excluded based on morphology of small packed tubules with scant cytoplasm and on immunohistochemical expression of CD57 and WT1 instead of CK7, AMACR, and EMA seen in MTSCC.

Percutaneous USG-guided biopsy in locally advanced, or metastatic renal carcinoma is of great use and is gaining popularity.[30] In current series, four patients were diagnosed as MTSCC on biopsy based on characteristic histological and IHC features.

The biological behavior of MTSCC is considered indolent, at least in organ confined stage (stages I and II), wherein radical or partial nephrectomy is considered the treatment of choice. In our series, surgically treated stage I and stage II tumors have excellent prognosis without recurrence with longest follow-up of 8 years. Metastatic disease at presentation (n = 3) and locally advanced disease (n = 1) were noted in our series which argues against the low-grade biological behavior of this tumor. Rare cases of local recurrence, metastasis, [4,7-11] or sarcomatoid transformation[8],[10],[12],[13],[14] have been described in the literature. A brief literature review has been detailed in [Table 4].[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44]
Table 4: Few highlighted studies cases of MTSCC


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In conclusion, MTSCC is a rare renal neoplasm with characteristic histomorphology. Diagnosis requires awareness of this entity and a diligent pathological examination of resected specimen. Biologic behavior is difficult to predict with current tools, and more studies, including biomarker development, are needed to enhance our understanding of this rare renal tumor.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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