54

The Korean Journal of Pathology2008; 42: 54-9

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that hasonly been recently described. Furthermore, a case of MTSCC associated with a simultaneouslung cancer in the same patient has never been reported in the literature. In this paper, wedescribe a kidney tumor that was detected during staging work-up in a 72-year-old lung can-cer patient. The kidney tumor was removed and shown to exhibit histological and immunophe-notypic features of MTSCC, completely distinct from the pulmonary adenocarcinoma. In addi-tion, this case was unique because it was characterized by neuroendocrine differentiation aswell as p53 and Ki-67 overexpression in tumor cells. Therefore, we report a case of MTSCCdiagnosed in a patient with pulmonary adenocarcinoma and describe the detailed histologicand immunohistochemical features of MTSCC.

Key Words : Spindle cell carcinoma; Kidney neoplasm; Lung cancer; Multiple primary neo-plasm

Seog-Yun Park∙∙Gyeong Hoon KangJae Y. Ro1∙∙Jennifer Black1

Jinsoo Chung2∙∙Kang Hyun Lee2

Eun Kyung Hong2∙∙Weon Seo Park2

54

Mucinous Tubular and Spindle Cell Carcinoma of Kidney Occurring in a

Patient with Pulmonary Adenocarcinoma

54 54

Corresponding AuthorWeon Seo Park, M.D.Department of Pathology, National Cancer Center,809 Madu1-dong, Ilsandong-gu, Goyang 410-769,KoreaTel: 031-920-1744 Fax: 031-920-0002E-mail: thymus@ncc.re.kr

Department of Pathology, Seoul NationalUniversity College of Medicine, Seoul,Korea; 1Weill Medical College of CornellUniversity, the Methodist Hospital,Houston, TX, USA; 2National CancerCenter, Goyang, Korea

Received : June 27, 2007Accepted : October 25, 2007

Mucinous tubular and spindle cell carcinoma (MTSCC) ofthe kidney is a novel neoplastic entity that has only recentlybeen described.1 The classic histological profile of this tumor isan admixture of low-grade tubular cuboidal cells with an arrayof spindle cells in a mucinous background.2-4 MTSCC is believedto originate from the distal nephron and to have a favorable clini-cal course.2,4,5 Previous reports have described a histological spec-trum and morphological variation in these tumors. The immuno-histochemical profile reported for this tumor has varied in dif-ferent studies.4-6

Because MTSCC has only recently been recognized, and fewcases have been reported, the association of MTSCC and lungcancer in the same patient has not been reported in the literature.In the present article, we report a case of MTSCC in a patientwith pulmonary adenocarcinoma. The kidney tumor was mor-phologically and immunohistochemically distinct from the lungcancer and showed spindle cell proliferation in the majority ofthe tumor with only small areas containing the tubular compo-nent with extracellular mucin accumulation.

CASE REPORT

Clinical summary

A 72-year-old man presented with a month-long history ofcoughing productive of blood-tinged sputum. The patient hadno other significant past medical history. A computerized tomo-graphic (CT) examination of the chest showed a spiculated nod-ule in the left upper lobe of the lung. A diagnosis of pulmonarycancer was suspected, and a metastatic survey was performed,which revealed no evidence of metastatic disease in the brain orbone. However, abdominal CT showed an exophytic right renalmass, which was clinically interpreted to be a metastatic lesion(Fig. 1A). A transbronchial biopsy was performed, resulting ina diagnosis of adenocarcinoma of the lung. A subsequent leftupper lobectomy confirmed the biopsy results. The patient thenreceived a combined chemotherapy regimen consisting of 4 cyclesof Padexol and carboplatin. Despite chemotherapy, no remark-able change was noted in the renal mass after 6 months, and a

Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of Kidney 55

radical nephrectomy was undertaken due to the possibility ofprimary renal cell carcinoma. The patient is alive and well 3

months after nephrectomy.

Fig. 2. Photomicroscopes of kidney tumor and metastatic lesion. (A) Most tumor cells show a predominant pattern of regular spindle cellsarranged in sheets resembling sarcoma. (B) Foci of cuboidal cell proliferation, forming cords and tubules are also seen, and the tubulesare separated by pale mucinous stroma. (C) Metastatic focus in a hilar lymph node is observed. (D) Alcian blue staining (pH 2.0) revealsthe presence of extracellular mucinous material.

C D

A B

Fig. 1. Computerized tomography of abdomen, and cut surface photograph of renal mass. (A) An exophytic renal mass was noted in thelower pole of the right kidney. (B) The tumor is well circumscribed and the cut surface is solid with multi-nodular configuration.

A B

56 Seog-Yun Park∙Gyeong Hoon Kang∙Jae Y. Ro, et al.

Pathologic findings

Gross findings

Examination of the nephrectomy specimen revealed a 5.5×4.0×3.5 cm cortical mass, located in the inferior pole of the

right kidney. It protruded into, but did not invade, the extrarenaladipose tissue (Fig. 1B). The tumor was well-circumscribed, butnot encapsulated. The cut surface of the tumor was pale-yellowwith a multi-nodular configuration and solid consistency. Nohemorrhage or necrosis was found. The left upper lobectomy

C D

E F

A B

Fig. 3. Representative immunohistochemical staining results. The tumor cells show strong reactivity to (A) epithelial membrane antigen,(B) vimentin, (C) renal cell carcinoma antigen, and (D) racemase, (E) p53 and (F) Ki-67.

Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of Kidney 57

specimen from the lung demonstrated a firm mass, measuring3.5×3.0×2.5 cm. Areas of hemorrhage and necrosis were seen.Microscopically, the tumor showed a moderately differentiatedadenocarcinoma. Peribronchial lymph nodes (20) and mediasti-nal lymph nodes (2) showed two foci of metastasis: one in eachof the peribronchial lymph nodes and mediastinal lymph nodes.

Microscopic findingsOn microscopic examination of the kidney tumor, the pre-

dominant pattern was a spindle cell proliferation, arranged infascicles (Fig. 2A). Additionally, small foci of epithelial cellsforming cords and tubules were recognized (Fig. 2B). In theseareas, elongated tubules were separated by pale mucinous stro-ma, and the tubules were composed of small cuboidal cells witheosinophilic cytoplasm. The nuclei of the tumor cells were small,round, and centrally located, without prominent nucleoli. Therewas no significant atypia. Mitoses and vascular invasion werenot observed. Metastasis to one hilar lymph node (1/1) was noted(Fig. 2C).

To exclude the possibility of metastatic carcinoma to the kid-ney originating from the lung, the lobectomy specimen wasalso reviewed. Microscopically, the lung cancer showed moder-ately differentiated, gland-forming adenocarcinoma withoutspindle cell areas. The tumor exhibited invasion into the viscer-al pleura and had one satellite tumor nodule. Metastases werefound in two regional lymph nodes (LN#4L). Therefore, patho-logical stage of the lung cancer was categorized as T4N2. Therewere no histologic similarities between the renal tumor and thepulmonary adenocarcinoma.

Histochemical and immunohistochemical findings

Alcian blue staining (pH 2.0) of the kidney tumor revealedthe presence of extracellular mucinous material in the tubularareas, but not in the spindle cell areas (Fig. 2D).

The tumor cells of MTSCC showed strong, diffuse stainingfor vimentin, epithelial membrane antigen, renal cell carcinomaantigen, and racemase (AMACR) (Fig. 3). Staining with cytok-eratin (CK) 7, prostate specific membrane antigen (PSMA), high-molecular-weight CK (34 E12), and low-molecular-weightCK (35 H11) revealed focal expression of moderate intensity.Additionally, neuron-specific enolase (NSE), chromogranin, synap-tophysin, and CD56 were weakly and focally expressed. p53 wasstrongly expressed in 5% (Fig. 3E), and Ki-67 was expressed in20% (Fig. 3F). The tumor cells were completely negative forpan CK (AE1/AE3), CK 18, CK 19, CD10, CD15, C-kit, villin,and thyroid transcription factor 1 (TTF-1). The tumor cells in

the lymph node were immunohistochemically identical to thoseseen in the kidney tumor and were negative for TTF-1. In con-trast, the lung tumor cells were strongly positive for TTF-1.

DISCUSSION

The recent WHO classification system has recognized MTSCCas a distinct entity of renal cell carcinoma, exhibiting a mixedpattern of tubules and a surrounding spindle cell proliferationwithin a myxoid stroma, showing low-grade nuclear features.1

Reported cases have shown a female predominance and benignclinical outcome.1-5 MTSCC can easily be diagnosed by histolo-gy alone, because of its characteristic histologic appearance. How-ever, morphologic diversity of MTSCC has been reported andmay create diagnostic difficulty when the histological featuresare not typical. In the present case, there were some unusualhistological features. For example, extracellular mucin and theclassic well-defined tubular architecture were noted only focal-ly. Thus, our case was a diagnostic challenge, as the dominantspindle cell component resembled sarcomatoid renal cell carci-noma or a mesenchymal tumor of the kidney. If the tumor hadnot been sampled adequately, the small foci of tubular architec-ture may have been overlooked, leading to misdiagnosis. There-fore, it is important that careful microscopic examination ofmultiple representative sections be performed to identify fea-tures of a less common lesion like MTSCC.

The cell lineage and origin of MTSCC still remains undeter-mined.5,6 Initially, Parwani et al. suggested that the morpholog-ic and ultrastructural configuration of MTSCC is similar to thenormal loop of Henle, and therefore believed that it originatedfrom the distal nephron.4 On the other hand, Sun et al. showedCD15 positivity and ultrastructural findings of mitochondriaand glycogen, favoring proximal tubule differentiation.6 Shen etal. also support the belief that this tumor most likely originatesfrom the proximal tubules and suggested that it actually repre-sents papillary renal cell carcinoma with spindle cell features.7

On immunohistochemistry in our case, the tumor was positivefor markers of the proximal tubules (AMACR) as well as formarkers of the distal nephron (EMA and CK7). Therefore, theline of differentiation of MTSCC remains unclear because of vari-ability of immunohistochemical results and electron microscopicfeatures. Further studies may help to more accurately determinethe origin of this rare tumor.

Interestingly, the tumor cells were immunohistochemicallypositive for endocrine markers such as NSE, chromogranin, synap-

58 Seog-Yun Park∙Gyeong Hoon Kang∙Jae Y. Ro, et al.

tophysin, and CD56 in our case. Jung et al. also reported thatsome MTSCC cases have shown positivity for endocrine markers.So neuroendocrine differentiation should be noted as anotherimmunohistochemical feature in the spectrum of MTSCC.8 Pre-vious electron microscopy studies have also revealed that thesetumors contain cytoplasmic neurosecretory granules.8

To date, fewer than 100 cases of MTSCC have been reported.3,9

Metastasis was identified in only 2 of these cases, with only region-al lymph node metastasis and no distant metastasis.3,9 We reportan additional case of metastatic MTSCC to a regional lymphnode. In our case, the percentage of p53 positive cells was above5% with strong intensity, which is different from other report-ed non-metastatic cases and may suggest an association betweenp53 activity and metastasis in MTSCC. Blandamura et al. foundthat p53 positivity had a significant correlation with metastasisin clear cell renal cell carcinoma (CCRCC).10 Pinto et al. also sug-gested that p53 overexpression correlates with lower disease-related survival in CCRCC.11 Since the two previously reportedmetastatic MTSCC cases were not stained with p53, the impor-tance of positivity of p53 and regional lymph node metastasiswith respect to clinical outcome is unclear. However, the factthat many cases that showed negative staining of p53 exhibitedno metastasis may support the possibility of correlation of posi-tive p53 staining and metastasis. Furthermore, Ki-67 was strong-ly expressed in 20% of tumor cell nuclei in our MTSCC case,which is unusual in these tumors. There were no reported casesof high Ki-67 proliferative activity in the previously reportedMTSCC cases.2,12

Simultaneous occurrence of lung cancer and renal mass usuallyhappens in the setting of tumor metastasis. However, separateprimary renal cell carcinoma can occur.13 Failure of the metastat-ic tumor to respond to therapy that is effective in the primarytumor raises the possibility that the presumed metastasis mayactually represent a second primary tumor, as occurred in ourcase. Therefore, careful histologic evaluation is required to deter-mine the nature of the presumed metastatic tumor. To the bestof our knowledge, this is the first reported case of lung adeno-carcinoma and MTSCC of the kidney occurring simultaneouslyin the same patient.

According to the diagnostic criteria by Warren & Gates, adouble cancer is classified as a synchronous type or a metachronoustype. Since the MTSCC was found less than 1 year after lungcancer had been found, our double cancer could be classified asa synchronous type. But, there are few reports of double cancerinvolving MTSCC, and few studies have reported the treatmentand 5-year disease survival rate of patients with multiple prima-

ry malignancies of different histologic types, as observed in ourcase. However, it is believed that the neoplasm with the lowest5-year disease survival rate should be treated first in cases of mul-tiple primary malignancies of different histologic types, becauseit has the greatest potential to shorten the patient’s life. In ourcase, the lung cancer had to be treated first because of its lower5-year disease survival rate, although high positivity of Ki-67and p53 was observed in MTSCC.

In summary, we report one case of MTSCC with regional lymphnode metastasis, occurring in a lung cancer patient. Accordingto our review of the literature, this is the first case report involv-ing a concurrent MTSCC of the kidney and pulmonary adeno-carcinoma. The kidney tumor revealed neuroendocrine differen-tiation as well as p53 and Ki-67 overexpression. Expression ofp53 staining and Ki-67 overexpression may correlate with aggres-sive behavior and may be related to the lymph node metastasisseen in this case. However, to determine the true significance ofp53 and Ki-67 overexpression in MTSCC, additional studieswith long-term follow-up will be needed.

REFERENCES

1. Eble JN, Sauter G, Epstein JI, Sesterhenn, ed. World Health Organi-

zation classification of tumors. Pathology and Genetics of Tumors

of the Urinary System and Male Genital Organs. Lyon: Internation-

al Agency for Research on Cancer (IARC) Press; 2004.

2. Aubert S, Duchene F, Augusto D, et al. Low-grade tubular myxoid

renal tumors: a clinicopathological study of 3 cases. Int J Surg Pathol

2004; 12: 179-83.

3. Hes O, Hora M, Perez-Montiel DM, et al. Spindle cell and cuboidal

renal cell carcinoma (loopoma). 10 case reports. Cas Lek Cesk 2004;

143: 169-73.

4. Parwani AV, Husain AN, Epstein JI, Beckwith JB, Argani P. Low-

grade myxoid renal epithelial neoplasms with distal nephron dif-

ferentiation. Hum Pathol 2001; 32: 506-12.

5. Paner GP, Srigley JR, Radhakrishnan A, et al. Immunohistochemi-

cal analysis of mucinous tubular and spindle cell carcinoma and

papillary renal cell carcinoma of the kidney: significant immunophe-

notypic overlap warrants diagnostic caution. Am J Surg Pathol

2006; 30: 13-9.

6. Sun W, McGregor DK, Ordonez NG, Ayala AG, Caraway NP. Fine

needle aspiration cytology of a low grade myxoid renal epithelial

neoplasm: a case report. Acta Cytol 2005; 49: 525-9.

7. Shen SS, Ro JY, Tamboli P, et al. Mucinous tubular and spindle cell

carcinoma of kidney is probably a variant of papillary renal cell

Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of Kidney 59

carcinoma with spindle cell features. Ann Diagn Pathol 2007; 11:

13-21.

8. Jung SJ, Yoon HK, Chung JI, Ayala AG, Ro JY. Mucinous tubular

and spindle cell carcinoma of the kidney with neuroendocrine dif-

ferentiation: report of two cases. Am J Clin Pathol 2006; 125: 99-104.

9. Ferlicot S, Allory Y, Comperat E, et al. Mucinous tubular and spin-

dle cell carcinoma: a report of 15 cases and a review of the literature.

Virchows Arch 2005; 447: 978-83.

10. Blandamura S, Giacomelli L, Leo G, Segato P, Ninfo V. Nuclear

maspin detection in renal cell tumours: possible diagnostic role and

correlation with p53 status. Histopathology 2006; 49: 274-82.

11. Pinto AE, Monteiro P, Silva G, Ayres JV, Soares J. Prognostic biomark-

ers in renal cell carcinoma: relevance of DNA ploidy in predicting

disease-related survival. Int J Biol Markers 2005; 20: 249-56.

12. Brandal P, Lie AK, Bassarova A, et al. Genomic aberrations in muci-

nous tubular and spindle cell renal cell carcinomas. Mod Pathol

2006; 19: 186-94.

13. Onishi T OY, Suzuki H, Asano K, et al. Study on the clinical charac-

teristics of double cancers associated with renal cell carcinoma.

Nippon Hinyokika Gakkai Zasshi 1998; 89: 808-15.