Metastatic mucinous tubular and spindle cell carcinoma of the kidney: Case report and literature review

Abstract

Mucinous tubular and spindle cell carcinoma is a rare renal neoplasm first classified by the WHO in 2004. It typically consists of low-grade cuboidal cells in tightly packed tubules, merging with spindle cells in a myxoid stroma with basophilic mucin. High-grade features, including sarcomatoid transformation, necrosis, and vascular invasion, are associated with poor prognosis and metastasis. Here, we present the second reported case of mucinous tubular and spindle cell carcinoma metastasizing to bone despite lacking high-grade features.

Introduction

Renal cell carcinoma (RCC) represents around 2% of all malignancies globally and accounts for 2% of cancer-related mortality, with clear cell RCC being the predominant subtype in this demographic group. ¹ Mucinous tubular and spindle cell carcinoma (MTSCC) was identified as a unique and relatively uncommon renal tumor subtype in the 2004 World Health Organization classification of adult renal epithelial neoplasms. ² An association with renal calculi was documented by Hes et al., ³ whereas Nouh et al. ⁴ reported its presence in patients long-term dialysis.

MTSCC is categorized into two morphological variants: the classic form, which contains abundant (>50%) extracellular mucin, and the mucin-poor form, characterized by minimal or absent extracellular mucin on hematoxylin and eosin staining. ⁵ Some tumors may undergo high-grade transformation, marked by high-grade nuclei, elevated mitotic activity, necrosis, vascular invasion, and occasionally sarcomatoid transformation. ¹ While high-grade transformation is typically linked to distant metastasis and poor outcomes, metastasis has also been documented in rare tumors with classic morphology. ¹

To the best of our knowledge, this represents the second documented case of mucin-poor MTSCC lacking sarcomatoid transformation that has metastasized to bone.

Case presentation

A 36-year-old male presented with progressive bilateral flank pain for 3 days, with a history of kidney stones. Physical examination was unremarkable. Computed tomography scan revealed a 1.8 × 1.4 cm ill-defined hypodense lesion in the right kidney, along with complete resolution of a previous obstructive right vesicoureteric stone. Magnetic resonance imaging (MRI) showed a solid right interpolar renal lesion measuring 2 × 1 cm, with low T2 signal intensity. The radiological differential diagnosis included papillary RCC and lipid-poor angiomyolipoma.

The patient underwent a robotic partial nephrectomy. Gross examination revealed a well-defined, tan, firm lesion measuring 2 × 1 × 0.8 cm. Microscopic evaluation showed a well-circumscribed lesion located in the renal medulla, predominantly composed of compressed tubules (Figure 1) lined by cuboidal cells with conspicuous nucleoli, embedded within a sclerotic stroma. The peripheral areas spindle cell and focally displayed anastomosing tubules within scant mucinous stroma (Figure 2), with focal regions demonstrating clear cytoplasm (Figure 3). The tumor was confined to the kidney, with no evidence of papillary formation, sarcomatoid or rhabdoid differentiation, necrosis, or vascular invasion.

Figure 1.

Tumor cells forming tubules and embedded within a sclerotic stroma. Hematoxylin and eosin stain 400× magnification.

Figure 2.

A high-magnification image showing the spindle tumor cells some are forming tubules and embedded within a myxoid stroma. Hematoxylin and eosin stain 200× magnification.

Figure 3.

A high-magnification image showing the tumor cells with abundant clear cytoplasm. Hematoxylin and eosin stain 400× magnification.

Immunohistochemical staining showed positivity for PAX8 and AMACR (Figure 4), with focal positivity for CK7 and HMWCK. The tumor was negative for Melan-A and HMB45. The diagnosis was particularly challenging, as the tumor was predominantly medullary in location and composed largely of sclerotic stroma with compact tubules and no spindle cell component, features that closely resembled medullary fibroma. However, the overall tumor size, the presence of focal mucin within the tubules, and the supportive immunohistochemical profile enabled us to confirm the diagnosis of MTSCC. The final diagnosis was MTSCC, WHO/ISUP grade 2, stage T1a, then he comes under active surveillance.

Figure 4.

AMCAR immunohistochemical stain showing cytoplasm stain of tumor cells. AMCAR 200×.

During active surveillance, 6 months later, the patient developed spinal cord metastasis and he underwent cord decompression, and the pathological examination confirmed metastatic mucinous tubular and spindle cell renal carcinoma. One year thereafter, he presented with hip pain and difficulty walking. MRI demonstrated a marrow-infiltrating lesion involving the mid left anterior acetabular wall with cortical breakthrough; the findings were most consistent with metastatic disease. The patient then began radiation therapy for the bone lesion.

Discussion

MTSCC was originally identified as a distinct and uncommon renal tumor subtype in the 2004 World Health Organization classification of adult renal epithelial neoplasms. ² It represents <1% of all renal tumors and shows a female predominance (M:F; 1.3:4), occurring over a wide age range (13–84 years). ¹ Alterations involving both alleles of Hippo pathway tumor suppressor genes are frequently observed. ¹ Hes et al. reported a link to renal calculi, a finding that corresponded with our case, whereas Nouh et al. described occurrences in patients who had been on long-term dialysis more than a decade. Although, initially it believed to arise from the distal nephron, later studies demonstrated substantial morphological and immunohistochemical similarities between MTSCC and papillary RCC, which exhibits features typical of proximal tubular epithelium. ⁶ Therefore, the exact origin of MTSCC remains uncertain. Classically, the tumor is composed of compact, elongated, interconnected tubules lined by low-grade cuboidal cells that merge with spindle cells in a myxoid stroma rich in basophilic extracellular mucin. ¹ Two morphological subtypes are described: classic, characterized by abundant (>50%) mucin can be highlighted by Alcian blue staining, and mucin-poor, which shows minimal to no mucin on hematoxylin and eosin sections. ⁵ Our case adds to the small number of mucin-poor cases that have been described in the literature.^6,7 Additional uncommon features may include a dominant epithelial or spindle cell component, focal clear or eosinophilic cytoplasm, foamy macrophages, and papillary structures. ⁸ Features of high-grade transformation include nuclear atypia, increased mitotic activity, necrosis, vascular invasion, and sarcomatoid changes represented by expansile high-grade spindle cells area. ¹ Tumor cells in both tubular and spindle components typically express PAX8, low-molecular-weight cytokeratin (CK8/18, CK19, CK7), AMACR, and E-cadherin, with variable staining for high-molecular-weight keratins and vimentin, while CD10, CD15, and RCC markers are frequently negative. ⁹ High-grade tumors often show elevated Ki-67 proliferation indices and increased nuclear p53 accumulation. ⁴ The most common differential diagnosis is papillary RCC, as some tumors of MTSCC may exhibit papillary architecture and share overlapping immunohistochemical features, including positivity for CK7 and AMACR. However, in the present case, the absence of papillary architecture argues against this diagnosis. Another important differential consideration is RCC with sarcomatoid differentiation, which is characterized by a sarcomatoid component occurring adjacent to or arising from a conventional RCC subtype, such as clear cell RCC, papillary RCC, or chromophobe RCC. The typical morphology of MTSCC is associated with losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. In contrast, tumors that share overlapping features with papillary RCC exhibit a more variable pattern of chromosomal changes, including both losses and gains—most notably gains of chromosomes 7 and 17. ⁹ Although the WHO 2004 classification described MTSCC as low-grade and indolent, several reports have since documented aggressive behavior with high-grade transformation. Consequently, the 2016 WHO classification removed the earlier assumption of indolence. ⁵ Tumors exhibiting high-grade transformation commonly metastasize and may lead to mortality, with metastatic disease most frequently arising in cases demonstrating sarcomatoid differentiation. ¹⁰ To our knowledge, this represents only the second reported case of mucin-poor MTS RCC lacking sarcomatoid features that metastasized to bone. ¹¹

Conclusion

MTSCC is an uncommon renal neoplasm characterized by a wide and often overlapping spectrum of morphological features, which can pose significant diagnostic challenges and may require careful correlation of histopathological, immunohistochemical, and sometimes molecular findings for accurate classification. Although it is generally considered a low-grade tumor with relatively indolent behavior, emerging evidence indicates that its biological potential may be more variable than previously appreciated. This heterogeneity underscores the importance of thorough diagnostic evaluation and vigilant clinical management. In particular, close and long-term follow-up is essential, as cases of MTSCC have been reported to develop metastatic disease even in the absence of conventional histological features typically associated with aggressive behavior, highlighting the need for ongoing surveillance despite an initially favorable appearance.