Fine Needle Aspiration Biopsy ofRenal Mucinous Tubular andSpindle Cell Carcinoma:Report of Two CasesDeborah A. Marks-Jones, M.D.,1 Debra L. Zynger, M.D.,1

Anil V. Parwani, M.D., Ph.D.,1 and Guoping Cai, M.D.1,2*

Mucinous tubular and spindle cell carcinoma (MTSCC) is arare renal tumor. Here we report two cases of MTSCC whichwere initially evaluated by fine needle aspiration biopsy (FNAB)and followed by surgical resection of the tumors. The cytomor-phologic features of MTSCC were characterized by aggregatesof relatively uniform, predominantly oval to spindle cellsintermixed with abundant metachromatic myxoid matrix. Onlyrare epithelioid tumor cells with vacuolated cytoplasm werepresent. Immunohistochemically, the tumor cells were positivefor CK7, CK19, CD10, vimentin, E-cadherin, alpha-methyl CoAracemase, and negative for CK903 and CK20. EMA and car-bonic anhydrase IX immunoreactivity was seen in one of the twocases. Multiple chromosomal losses involving chromosomes 1, 2,17 and likely chromosome 7 were revealed by fluorescence insitu hybridization (FISH). These cytomorphologic, immunophe-notypic, and cytogenetic features were helpful for including thisentity in the differential diagnosis of renal cell carcinomas.Diagn. Cytopathol. 2010;38:51–55. ' 2009 Wiley-Liss, Inc.

Key Words: mucinous tubular and spindle cell carcinoma;kidney; fine needle aspiration biopsy; cytomorphology

Mucinous tubular and spindle cell carcinoma (MTSCC)

of the kidney is a rare, newly recognized low-grade re-

nal epithelial neoplasm.1–5 It has distinct histomorpho-

logic features, characterized by tightly packed small

elongated tubules embedded in pale mucinous matrix.

The epithelial cells that line the tubules are cuboidal but

often have spindle cell configuration. MTSCC seems to

have a favorable prognosis as compared to other renal

cell carcinomas.5 However, a significant sarcomatoid

component can be seen in some cases of MTSCC, which

may be associated with a more aggressive clinical

course.6–8

MTSCC, though histomorphologically distinct, may

impose a diagnostic challenge in small specimens such

as fine needle aspiration biopsy (FNAB). There have

been only four reported cases in the English literature

describing the cytomorphologic features of the tu-

mor.9–12 Here we report two cases of MTSCC of the

kidney which were initially evaluated by FNAB and

confirmed with surgical follow-up. Their cytomorpho-

logic, immunophenotypic, and cytogenetic features are

described.

Case Reports

Case 1

The patient is a 51-year-old man with a history of lung

carcinoma, status post right upper lobectomy, and liver

transplant for hepatitis C. Routine laboratory work

revealed an elevated creatinine (1.8 mg dL�1; normal

range 0.5–1.2 mg dL�1) and blood urea nitrogen (31 mg

dL�1; normal range 7–18 mg dL�1). Renal ultrasound

identified a 2.7 cm hypoechoic, solid mass in the mid

pole of the left kidney. Follow-up MRI confirmed the

presence of a 2.7-cm mass which was hypovascular,

rounded, and solid with possible hemorrhage. The patient

underwent an ultrasound-guided FNAB of this renal mass

with a 25-gauge spinal needle. The aspirates were

smeared and stained with standard Diff-Quik and Papani-

colaou techniques. Additional aspirates were fixed in 4%

formalin solution and processed for a cell block. A cyto-

logical diagnosis of renal cell carcinoma with clear cell

1Department of Pathology, University of Pittsburgh Medical Center,Pittsburgh, Pennsylvania

2Department of Pathology, Yale University School of Medicine,New Haven, Connecticut

*Correspondence to: Guoping Cai, M.D., Department of Pathology,Yale University School of Medicine, 430 Congress Avenue, P. O. Box208023, New Haven, CT 06520-8023.E-mail: guoping.cai@yale.edu

Received 2 April 2009; Accepted 10 June 2009DOI 10.1002/dc.21151Published online 22 July 2009 in Wiley InterScience (www.

interscience.wiley.com).

' 2009 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 38, No 1 51

features was rendered. Subsequent partial nephrectomy

was performed 5 weeks after the FNAB, which resulted

in a diagnosis of MTSCC with pathological staging of

pT1aNxMx. The patient was followed for 16 months and

imaging studies show no evidence of local recurrence or

distant metastasis.

Case 2

The patient is a 54-year-old man with a past medical his-

tory significant for nephrolithiasis. A CT scan revealed

slight enlargement of the left kidney as well as perineph-

ric stranding and hydronephrosis with multiple calculi

bilaterally. A 5-cm solid mass was revealed in the lower

pole of the left kidney. An ultrasound-guided FNAB of

the renal mass was performed with a 25-gauge spinal nee-

dle. The Diff-Quik and Papanicolaou stained smear slides

as well as cell block sections were available for cytologi-

cal evaluation. The final cytopathologic diagnosis was re-

nal cell carcinoma. One week later, the patient underwent

a laparoscopic left nephrectomy. Histopathologic exami-

nation demonstrated a MTSCC of the kidney with patho-

logical staging of pT1bNxMx. The patient was followed

for 3 years and 3 months and showed no evidence of

local recurrence or distant metastasis.

Pathologic Findings

The aspirates for both cases were cellular and shared sim-

ilar cytomorphologic features. The aspirates revealed

loosely cohesive clusters of predominantly oval to spindle

tumor cells arranged in sheets, branching clusters or

pseudo-papillary aggregates (Fig. 1A). No definite fibro-

vascular cores were identified. Scattered tumor cells were

present singly, some as naked nuclei. Abundant amor-

phous, metachromatic mucinous/myxoid matrix was pres-

ent, often intimately intermingled with tumor cell clusters

(Fig. 1B). The matrix was magenta on the Diff-Quik stain

and pale blue on the Papanicolaou stain. The tumor cells

showed mild pleomorphism and had delicate cytoplasm

with indistinct cell borders and oval to spindle nuclei

with relatively smooth nuclear contours and conspicuous

Fig. 1. FNA cytomorphological features of mucinous tubular and spindle cell carcinoma of the kidney. The aspirates revealed clusters of epithelioid tospindle cells intermingled with metachromatic matrix (A: Diff-Quik, 3100). The tumor cells were predominantly oval to spindle shaped with blandcytomorphology (B: Papanicolaou, 3400; C: Diff-Quik, 3400). Few tumor cells had round nuclei and conspicuous cytoplasmic vacuoles (D: Diff-Quik, 3600). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

MARKS-JONES ET AL.

52 Diagnostic Cytopathology, Vol 38, No 1

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nucleoli. Distinct fine cytoplasmic vacuoles were present

in some of the tumor cells (Fig. 1C). In addition, a few

clusters of tumor cells with vacuolated cytoplasm and

round nuclei were also present (Fig. 1D).

Grossly, the tumors were 2.6 and 6 cm in size, respec-

tively, well-circumscribed and confined within the kidney

without capsular invasion. Focal hemorrhage was identified

in case 2. On histopathologic examination, both tumors

showed tightly packed elongated tubules with intervening

pale mucinous/myxoid matrix (Fig. 2A). The cells lining

the tubules were mainly oval to spindle shaped with rela-

tively bland nuclear features (Fig. 2B). However, focal

areas with epithelioid cells were also present (Fig. 2C).

Immunohistochemical studies were performed on the

cell-block sections and/or resection specimens with appro-

priate negative and positive controls. In both cases, the tu-

mor cells were immunoreactive with CK7, CK19, CD10,

vimentin, E-cadherin, alpha-methyl CoA racemase

(P504S), and negative for CK20, CK903 (Table I). The

immunostains for epithelial membrane antigen (EMA)

and carbonic anhydrase IX (CA-9) were positive in case 2

but negative in case 1.

Fluorescence in situ hybridization (FISH) studies with

probes for the centromeres of chromosomes 1, 2, 7, and 17

were performed on the surgical specimens. At our institution,

chromosomal losses are considered significant if present in

Fig. 2. Histomorphologic features of mucinous tubular and spindle cellcarcinoma of the kidney. The tumor showed tightly packed elongatedtubular structures embedded in a myxoid/mucinous stroma (A: H&E,340). The tubules were predominantly lined by oval to spindle cells (B:H&E, 3200). Focally, the lining cells had an epithelioid appearance (C:H&E, 3200). Color figure can be viewed in the online issue, which isavailable at www.interscience.wiley.com.]

Fig. 3. Cytogenetic features of mucinous tubular and spindle cell carcinomaof the kidney. Florescence in situ hybridization (FISH) studies with centro-meric probes demonstrated loss of the chromosomes 1 and 17, and to a lesserextent the chromosomes 2 and 7 (A and B). [Color figure can be viewed inthe online issue, which is available at www.interscience.wiley.com.]

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greater than 30% of cells and are considered artifactual if

seen in less than 20% of cells. The losses are indeterminate

if present in 20–30% of cells. Both cases showed significant

losses of chromosomes 1, 2, and 17, present as monosomies.

Loss of chromosomes 7 was significant in one case but con-

sidered indeterminate in the other (Table II, Fig. 3).

Discussion

The cytomorphologic features of MTSCC in this report

were characterized by clusters of relatively bland cells

intermixed with abundant metachromatic matrix. The tu-

mor cells seemed to be predominantly oval to spindle

with mild pleomorphism, which are similar to those previ-

ously described in FNAB aspirates,10,12 but differ from

the other with predominant epithelioid cell morphology.9

Based on the cytomorphologic features, MTSCC should

be differentiated from other renal neoplasms (Table III).

When spindle cells are the predominant morphology, the

differential diagnosis includes sarcomatoid renal cell car-

cinoma and angiomyolipoma. Papillary renal cell carci-

noma might have foci of spindle cells, which may mimic

MTSCC.13 In cases with more epithelioid cells, other re-

nal cell carcinomas such as conventional (clear cell) and

papillary variants as well as collecting duct carcinoma are

among the differential. The tumor cells in these entities

often show cytological atypia in contrast to the bland

cytomorphology seen in MTSCC. Furthermore, none of

these entities have abundant metachromatic matrix

although the lack of matrix does not exclude MTSCC

from the differential diagnosis as mucin-poor MTSCC has

been described.14 In addition, conventional (clear cell) re-

nal cell carcinoma might contain a small amount of meta-

chromatic basal membrane-like material.

There are conflicting results regarding the immunophe-

notypic profile of MTSCC.1–3,15–19 The most consistent

findings are the immunoreactivity for vimentin, EMA,

and alpha-methyl CoA racemase.2,3,15,16,20 However, only

one of our two cases was positive for EMA. The staining

for high molecular weight cytokeratin seems to be incon-

sistent, as does reactivity for CK19.1,2,16,18 Both of our

specimens were immunoreactive for CK19 but not for

high molecular weight cytokeratin (CK903). CD10, which

has previously been shown to be positive only in a

minority of MTSCC, was positive in both of our tumors.

In addition, one of our cases showed immunoreactivity

for carbonic anhydrase IX, a maker for proximal tubular

origin. There is only one other study of carbonic anhy-

drase IX in MTSCC in which the authors found the tumor

to be negative.21 Overall, MTSCC appears to express the

markers for both proximal and distal renal tubules and

shows immunophenotypical overlap with papillary renal

cell carcinoma and collecting duct carcinoma.

Different subtypes of renal cell carcinomas may display

unique chromosomal abnormalities. Conventional (clear

cell) renal cell carcinoma frequently show loss of chromo-

somal 3p,22 while papillary renal cell carcinoma is charac-

terized by gains of chromosomes 7 and 17.23 In chromo-

phobe renal cell carcinoma and renal oncocytoma, multiple

chromosomal losses are often present.24,25 Several studies

using comparative genomic hybridization (CGH) or FISH

have demonstrated chromosomal abnormalities in

MTSCC.3,16,26,27 The most consistent findings are multiple

chromosomal losses. In Rakozy’s study of five MTSCC

cases,3 CGH revealed multiple losses of chromosomes 1, 4,

6, 8, 9, 13, 14, 15, and 22. However, there are conflicting

results regarding chromosomal gains, particularly for chro-

mosomes 7 and 17.3,16,27 Cossu-Rocca et al.28 examined 10

MTSCC cases using FISH and reported no gains of 7 or

17, directly disputing previous results.27 In the present

study using interphase FISH, chromosomal losses involv-

ing chromosomes 1, 2, 17, and likely chromosome 7 were

identified. The overall results of cytogenetic studies do not

support the suggestion that MTSCC is a variant of papil-

lary renal cell carcinoma.19

In summary, MTSCC has distinct cytomorphologic fea-

tures characterized by clusters of epithelioid to spindle

cells intermixed with abundant myxoid matrix. MTSCC is

immunophenotypically similar to papillary renal cell car-

Table I. Immunophenotypic Features of Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

CK7 CK20 CK19 CK903 EMA CD10 VIM ECAD P504S CA-9

Case 1 + � + � � + + + + +Case 2 + � + � + + + + + �EMA, epithelial membrane antigen; VIM, vimentin; ECAD, E-cadherin; P504S, alpha-methyl CoA racemase; CA-9, carbonic anhydrase IX.

Table II. Cytogenetic Chromosomal Abnormalities of Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

CEP1 CEP2 CEP7 CEP17

1 Copy 2 Copy 1 Copy 2 Copy 1 Copy 2 Copy 1 Copy 2 Copy

Case 1a 69/78 (88.5%) 9/78 (11.5%) 20/60 (33.3%) 38/60 (63.3%) 15/63 (23.8%) 43/63 (68.3%) 52/77 (67.5%) 24/77 (31.2%)Case 2 51/60 (85%) 9/60 (15%) 40/60 (66.7%) 20/60 (33.3%) 22/60 (36.7%) 38/60 (63.3%) 44/60 (73.3%) 16/60 (26.7%)

aRare tumor cells in case one showed trisomies of chromosomes 2, 7, and 17.CEP, centromere enumeration probe.

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54 Diagnostic Cytopathology, Vol 38, No 1

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cinoma but they differ in their cytogenetic abnormalities.

Increasing awareness of MTSCC and its cytomorphologic,

immunophenotypic, and cytogenetic features would be

helpful to render a more precise diagnosis.

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Table III. Differential Diagnosis of Mucinous Tubular and Spindle Cell Carcinoma From Other Renal Cell Carcinomas

Cytomorophology Immunophenotype Cytogenetics

MTSCC Round, oval, spindle cells, mildpleomorphism, abundant matrix

EMA+, Vim+, P504S+, CK7+, CD10+/� Loss of multiple chromosomes

Sarcomatoid RCC Oval, spindle cells, atypia, no matrix EMA+/�, P504S�, CD10+/� UnknownClear cell RCC Round cells, variable atypia, rare matrix EMA+, Vim+, CD10+,

CK7-, P504S�, CA-9+Chromosome 3p deletion

Papillary RCC Round cells, variable atypia, no matrix EMA+, Vim+, CD10+/�, CK7+, P504S+ Gain of chromosomes 7 and 17Collecting ductcarcinoma

Round cells, atypia, no matrix EMA+/�, Vim+, CD10�,CK7+/�, P504S�, UEA-1+

Unknown

MTSCC, mucinous tubular and spindle cell carcionoma; RCC, renal cell carcinoma; EMA, epithelial membrane antigen; VIM, vimentin; P504S,alpha-methyl CoA racemase; CA-9, carbonic anhydrase IX; UEA-1, Ulex europaeus agglutinin-1.

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