Am J Clin Pathol 2006;125:99-104 99
© American Society for Clinical Pathology
Anatomic Pathology / MUCINOUS TUBULAR AND SPINDLE RCC
Mucinous Tubular and Spindle Cell Carcinoma
of the Kidney With Neuroendocrine Differentiation
Report of Two Cases
Soo Jin Jung, MD,1Hye Kyoung Yoon, MD,1Jae Il Chung, MD,2Alberto G. Ayala, MD,3
and Jae Y. Ro, MD3
Key Words: Mucinous tubular and spindle cell carcinoma; Neuroendocrine differentiation; Kidney
A b s t r a c t
We encountered 2 cases of mucinous tubular and
spindle cell carcinoma (MTSCC) during a short time. In
a 61-year-old man who had macroscopic hematuria for
1 month, the 14.5 × 14.0 × 12.0-cm resected tumor
involved the right middle aspect of the renal
parenchyma and compressed the renal pelvis. In an
asymptomatic 47-year-old man, a renal tumor was
found during an annual physical examination. The 3.5
× 3.0 × 2.0-cm tumor was located at the upper pole of
the right kidney. The histologic findings in both cases
were similar. Tumors consisted of tightly packed, small,
elongated tubules separated by pale mucinous stroma.
The tumor cells were cuboidal to spindled with
eosinophilic cytoplasm and low nuclear grade. Mitoses
were few or nonexistent and without abnormal figures.
Both tumors were immunoreactive for cytokeratin (CK)
cocktail (AE1/AE3), high-molecular-weight CK
(34βE12), low-molecular-weight CK (35βH11), CK7,
epithelial membrane antigen, E-cadherin, and vimentin.
The tumor cells also were reactive for neuron-specific
enolase, chromogranin, and synaptophysin. The
ultrastructure of the tumor cells contained abundant
mitochondria, junctional complex, and dense-core
We present 2 additional cases of MTSCC showing
typical morphologic features with neuroendocrine
In the recent World Health Organization classification,1
mucinous tubular and spindle cell carcinoma (MTSCC) was
introduced as a histologic variant of renal cell carcinoma (RCC).
This lesion initially was described as an unusual renal carcinoma
with prominent spindle cell change2and as a low-grade myxoid
renal neoplasm with distal nephron differentiation.3
The histologic spectrum of this tumor and the immuno-
histochemical profiles are variable. Histologically, these
tumors are characterized by elongated tubular and cord-like
architecture, cuboidal to spindled cells with low nuclear grade,
and a myxoid/mucinous stroma. The origin of MTSCC has
been suggested as the loop of Henle or collecting duct, but this
view is debatable.
We describe 2 patients with this type of renal neoplasm.
Both cases revealed immunohistochemical and ultrastructural
evidence of neuroendocrine differentiation.
Report of Cases
A 61-year-old man had macroscopic hematuria for 1
month. Computed tomography revealed a huge renal mass in the
right kidney. No metastatic lesions or lymph node enlargement
were noted, and laboratory data were within the normal ranges.
A 47-year-old man was found incidentally to have a mass
in the upper pole of his right kidney during an annual medical
checkup. He had no medical or family history of any malignan-
cy. All of his laboratory data were within the normal ranges.
Am J Clin Pathol 2006;125:99-104
© American Society for Clinical Pathology
Jung et al / MUCINOUS TUBULAR AND SPINDLE RCC
intercalated cells of the collecting duct have more numerous
mitochondria and tubulovesicular structures in the cytoplasm
than cells of the loop of Henle. However, these findings are non-
specific in distinguishing the cells of the loop of Henle from col-
lecting duct cells. Immunohistochemical profiles would seem to
favor collecting duct differentiation because collecting duct carci-
noma is the only type of renal carcinoma that consistently labels
with high-molecular-weight CK and Ulex europaeus agglutinin
and not with CD15, a good marker of proximal tubule differenti-
ation.17Rakozy et al9described that these tumors revealed no
reactivity for Tamm-Horsfall protein, a marker found in distal
convoluted tubules and the ascending loop of Henle, whereas
they positively reacted for epithelial membrane antigen and
peanut agglutinin, markers of collecting duct epithelium. Based
on their findings, they suggested that these tumors originated
from collecting duct epithelium. However, the case reported by
Sun et al13showed CD15 positivity and abundant mitochondria
and glycogen by ultrastructural examination, favoring proximal
tubule differentiation. It is clear that further studies are required to
better characterize the origin of this rare kidney tumor.
Rakozy et al9elucidated multiple losses of chromosomes
(1, 4, 6, 8, 9, 13-15, and 22) by using comparative genomic
hybridization; there was no 3p loss or mutation in the VHL
gene of their tumors. The most consistent gene alterations of
collecting duct carcinoma included losses of 8p and 13q,18
whereas chromophobe RCC showed losses in chromosomes 1,
2, 6, 10, 13, 17, and 21.19Accordingly, it might be considered
that the common genes involved in MTSCC also involve col-
lecting duct carcinoma and chromophobe RCC; therefore, the
origin of MTSCC seems to be genetically closer to the collect-
ing duct than the loop of Henle or proximal convoluted tubule.
We encountered 2 cases of MTSCC arising in 2 men, ages
47 and 61 years. Both tumors revealed neuroendocrine differen-
tiation. The significance of neuroendocrine differentiation and
the histogenesis of these tumors await the study of further cases.
Because there are overlapping features between MTSCC and
low-grade collecting duct carcinoma, further examination of
additional cases should be performed to better define the entities
of MTSCC and so-called low-grade collecting duct carcinoma.
From the Departments of 1Pathology, and 2Urology, Inje
University College of Medicine, Busan, Korea, and 3Pathology,
Cornell University, the Methodist Hospital, Houston, TX.
Address reprint requests to Dr Jung: Dept of Pathology, Inje
University College of Medicine, Pusan Paik Hospital, 633-165
Kaekeum-dong, Busanjin-ku, Busan, 614-735, Korea.
1. Srigley JR. Mucinous tubular and spindle cell carcinoma, In:
Eble JN, Sauter G, Epstein JI, et al, eds. Tumours of the Urinary
System and Male Genital Organs. Lyon, France: IARC Press;
2004:40. World Organization Classification of Tumours.
2. Srigley JR, Eble JN, Grignon DJ, et al. Unusual renal cell
carcinoma (RCC) with prominent spindle cell change possibly
related to the loop of Henle [abstract]. Mod Pathol.
3. Leroy X, Aubert S, Gosselin B. Low-grade myxoid renal
epithelial neoplasms with distal nephron differentiation: a
distinct clinicopathologic entity [letter]? Hum Pathol.
4. Parwani AV, Husain AN, Epstein JI, et al. Low-grade myxoid
renal epithelial neoplasms with distal nephron differentiation.
Hum Pathol. 2001;32:506-512.
5. Otani M, Shimizu T, Serizawa H, et al. Low-grade renal cell
carcinoma arising from the lower nephron: a case report with
immunohistochemical, histochemical and ultrastructural
studies. Pathol Int. 2001;51:954-960.
6. Hes O, Hora M, Perez-Montiel DM, et al. Spindle and
cuboidal renal cell carcinoma, a tumor having frequent
association with nephrolithiasis: report of 11 cases including a
case with hybrid conventional renal cell carcinoma/spindle
and cuboidal renal cell carcinoma components. Histopathology.
7. He Q, Ohaki Y, Mori O, et al. A case report of renal cell
tumor in a 45-year-old female mimicking lower portion
nephrogenesis. Pathol Int. 1998;48:416-420.
8. Kuroda N, Nakamura S, Miyazaki E, et al. Low-grade tubular-
mucinous renal neoplasm with neuroendocrine differentiation:
a histological, immunohistochemical and ultrastructural study.
Pathol Int. 2004;54:201-207.
9. Rakozy C, Schmahl GE, Bogner S, et al. Low-grade tubular-
mucinous renal neoplasms: morphologic,
immunohistochemical, and genetic features. Mod Pathol.
10. Hara N, Kawaguchi M, Koike H, et al. Low-grade renal
epithelial tumor originating from the distal nephron. Int J
11. Kuroda N, Toi M, Hiroi M, et al. Review of metanephric
adenoma of the kidney with focus on clinical and
pathobiological aspects. Histol Histopathol. 2003;18:253-257.
12. MacLennan GT, Farrow GM, Bostwick DG. Low-grade
collecting duct carcinoma of the kidney: report of 13 cases of
low-grade mucinous tubulocystic renal carcinoma of possible
collecting duct origin. Urology. 1997;50:679-684.
13. Sun W, McGregor DK, Ordonez NG, et al. Fine needle
aspiration cytology of low-grade myxoid renal epithelial
neoplasm: a case report. Acta Cytol. In press.
14. Stahl FE, Sighu GS. Primary carcinoid of the kidney: light and
electron microscopic study. Cancer. 1997;44:1345-1349.
15. Tetu B, Ro JY, Ayala AG, et al. Small cell carcinoma of the
kidney: a clinicopathologic, immunohistochemical, and
ultrastructural study. Cancer. 1987;60:1809-1814.
16. Raslan WF, Ro JY, Ordonez NG, et al. Primary carcinoid of
the kidney: immunohistochemical and ultrastructural studies
of five patients. Cancer. 1993;72:2660-2666.
17. Srigley JR, Eble JN. Collecting duct carcinoma of the kidney.
Semin Diagn Pathol. 1998;15:54-67.
18. Schoenberg M, Cairns P, Brooks JD, et al. Frequent loss of
chromosome arms 8p and 13q in collecting duct carcinoma
(CDC) of the kidney. Genes Chromosomes Cancer. 1995;12:76-80.
19. Kuroda N, Toi M, Hiroi M, et al. Review of chromophobe
renal cell carcinoma with focus on clinical and pathobiological
aspects. Histol Histopathol. 2003;18:165-171.