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Pathology – Research and Practice

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Teaching cases

Mucinous tubular and spindle cell carcinoma of the kidney with

prominent papillary component, a non-classic morphologic variant.
A histologic, immunohistochemical, electron microscopic and
fluorescence in situ hybridization study
Borislav A. Alexiev ∗ , Allen P. Burke, Cinthia B. Drachenberg, Stephanie M. Richards,
Ying S. Zou
Department of Pathology, University of Maryland Medical Center, Baltimore, MD, USA

a r t i c l e i n f o a b s t r a c t

Article history: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor with relatively indo-
Received 6 December 2013 lent behavior. Non-classic morphological variants have not been well studied and rarely been reported.
Received in revised form 10 February 2014 We report a challenging case MTSCC with a peculiar morphology in a 42-year-old man, arising in a
Accepted 10 March 2014
background of end-stage renal disease (ESRD). Predominant areas with extensive papillary architecture,
psammoma bodies and stromal macrophageal aggregates, reminiscent of a papillary renal cell carcinoma
Keyword:
(papillary RCC), were intermixed with foci that transitioned into a MTSCC-like morphology exhibiting
Renal cell carcinoma
elongated tubules and a low grade spindle cell component in a background of mucinous stroma. Immuno-
histochemistry demonstrated diffuse positivity for P504s/AMACR and vimentin in tumor cells. Focal
positivity for RCC, CD10 and CK7 was also noted. Kidney-specific cadherin, cytokeratin 34betaE12 and
TFE3 stains were negative in the tumor. The major differential diagnostic considerations were papillary
RCC, clear cell papillary RCC, and Xp11.2 translocation carcinoma. Negative FISH studies for trisomy 7
and 17 in both papillary and spindled components supported the diagnosis of MTSCC. The ultrastruc-
tural profile was not entirely indicative of the cellular origin of the tumor. Cytogenetic analysis should
be performed in atypical cases of MTSCC for precise diagnosis.
© 2014 Elsevier GmbH. All rights reserved.

Introduction ultrastructural, and fluorescence in situ hybridization (FISH) fea-

tures.
Mucinous tubular and spindle cell carcinoma (MTSCC) of
the kidney is a recently described entity in the World Health Clinical history
Organization classification with a relatively indolent behavior
[2,4–7,9–13,15–18]. MTSCC preferentially affects females [2]. The A 42-year-old man with end-stage renal disease (ESRD), status
classic MTSCC is a renal neoplasm characterized by small, elon- post cadaveric renal transplant in 2004, was admitted with right
gated tubules lined by cuboidal cells and/or cords of spindle cells lower quadrant pain. CT and MR imaging demonstrated a 5 cm right
separated by pale mucinous stroma [2,4–7,9–13,15]. Non-classic renal interpolar solid mass concerning for RCC. A total nephrectomy
morphologic variants have rarely been reported [4,5]. We present was performed.
a challenging case of MTSCC mimicking papillary renal cell car-
cinoma (RCC) and describe its histologic, immunohistochemical,
Material and method

Representative tissue sections from the total nephrectomy

∗ Corresponding author at: Department of Pathology, NBW85, University of Mary-
land Medical Center, 22 S Greene Street, Baltimore, MD 21201, USA.
Tel.: +1 4103285286.
E-mail address: balexiev@umm.edu (B.A. Alexiev).
were fixed in 10% buffered formalin and embedded in paraf-
fin. For routine microscopy, 4-␮-thick sections were stained with
hematoxylin–eosin (H&E) and alcian blue (pH 2.5). Immuno-
histochemical staining was performed using an automated
immunostainer (Leica Bond-III, Leica Biosystems, Buffao Grove, Il)

http://dx.doi.org/10.1016/j.prp.2014.03.002
0344-0338/© 2014 Elsevier GmbH. All rights reserved.

Please cite this article in press as: B.A. Alexiev, et al., Mucinous tubular and spindle cell carcinoma of the kidney with prominent
papillary component, a non-classic morphologic variant. A histologic, immunohistochemical, electron microscopic and fluorescence
in situ hybridization study, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.002
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2 B.A. Alexiev et al. / Pathology – Research and Practice xxx (2014) xxx–xxx

Fig. 1. Mucinous tubular and spindle cell carcinoma (MTSCC). (a) Note papillary architecture and spindled component. Hematoxylin–eosin stain, 40×. (b) Note well-
formed papillae. Hematoxylin–eosin stain, 100×. (c) Note MTSCC features. Hematoxylin–eosin stain, 100×. (d) Note transition of papillary carcinoma-like into a MTSCC-like
morphology. Hematoxylin–eosin stain, 100×.

and BondRefinePolymerTM biotin-free DAB detection kit. The fol-
lowing antibodies were used: RCC (prediluted, mouse monoclonal,
Ventana); vimentin, CD10, CK7 (prediluted, mouse monoclonal,
Leica); P504s/AMACR and TFE3 (prediluted, rabbit monoclonal,
Cell Marque), cytokeratin 34betaE12 and kidney-specific cad-
herin (prediluted, mouse monoclonal, Cell Marque), and PAX8
(prediluted, rabbit polyclonal, Cell Marque). A positive nuclear,
cytoplasmic and/or membranous expression in 10% or more of
neoplastic cells qualified as “positive (+)”. Fluorescence in situ
hybridization (FISH) was performed with centromeric ␣-satellite
DNA probes for chromosome 7 (CEP 7, D7Z1, Spectrum Green)
and chromosome 17 (CEP 17, D17Z1, Spectrum Orange), accord-
ing to the manufacturer’s instructions (Abbott Molecular Inc.). The
slides were evaluated under a Zeiss Axioplan 2 microscope (ZEISS
Inc.), using a 100× objective. The images were acquired with a CCD
camera and analyzed with CytoVision Software (Leica Biosystems
Inc.). For each probe, 300 nuclei were scored in areas marked to
correspond with hematoxylin–eosin sections by two readers. For
electron microscopy, tissue samples first were fixed in formalin
and then in 2.5% glutaraldehyde, postfixed in 1% osmium tetrox-
ide, dehydrated, and embedded in epoxy resin. Thin sections from
both cases were stained with uranyl acetate and lead citrate and
examined on a JEM 1200 transmission electron microscope.
Results
Grossly, the tumor was well circumscribed (4.7 cm × 4.6 cm ×
2.9 cm), located between the superior and inferior kidney poles,
surrounded by a thin fibrous pseudocapsule. The cut surface
appeared tan with yellow streaks. Microscopically, examination
of hematoxylin and eosin-stained tissue section demonstrated a
well circumscribed, partially encapsulated lesion with a pecu-
liar morphology, arising in a background of ESRD. Predominant
areas with extensive papillary architecture, multifocal psammoma
bodies and abundant stromal macrophageal aggregates, reminis-
cent of a papillary RCC, were intermixed with foci that transitioned
into a MTSCC-like morphology exhibiting elongated tubules and
a low grade spindle cell component in a background of mucinous
and hyalinized stroma (Figs. 1a–d and 2a–c). The tumor cells were
columnar, cuboidal or spindled with eosinophilic cytoplasm and
low nuclear grade. Focal clear cells in the papillary areas were
also noted. Mitoses were rare (0–1/10 high power fields). Tumor
necrosis was not observed. Alcian blue stain demonstrated abun-
dant stromal acidic mucinous material in both papillary and tubular
and spindle cell components (Fig. 2d). The nuclear atypia corre-
sponded to Fuhrman grade 2. The pathologic stage was pT1bNxMx.
Immunohistochemistry demonstrated strong diffuse positivity for
PAX8, P504s/AMACR (Fig. 3a) and vimentin in the tumor. Focal pos-
itivity for RCC (Fig. 3b), CD10 and CK7 (Fig. 3c) was also noted.
Kidney-specific cadherin, cytokeratin 34betaE12 and TFE3 stains
were negative in the tumor. The FISH studies revealed a normal
copy number for chromosomes 7 and 17 in both papillary and
spindled components (Fig. 3d). Electron microscopic examination
demonstrated low columnar, cuboidal and spindle cells with low
nuclear to cytoplasmic ratio. The nuclei were relatively small with
dispersed chromatin, smooth nuclear membrane, and small nucle-
oli. The tumor cells contained scant cytoplasmic organelles and
intermediate filaments. Short apical microvilli and well-developed
desmosomes at the site of attachment between the apposing cell
membranes were present. The stroma contained numerous foamy
macrophages.
Discussion
The present case, unlike the classic MTSCC, presented with
an extensive papillary architecture, psammoma bodies and stro-
mal macrophages reminiscent of a papillary RCC. The papillary
component was intermixed throughout the tumor with foci that

Please cite this article in press as: B.A. Alexiev, et al., Mucinous tubular and spindle cell carcinoma of the kidney with prominent
papillary component, a non-classic morphologic variant. A histologic, immunohistochemical, electron microscopic and fluorescence
in situ hybridization study, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.002
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Fig. 2. Mucinous tubular and spindle cell carcinoma (MTSCC). (a) Note well-formed papillae lined by columnar cells with eosinophilic or clear cytoplasm and low-grade
nuclei. Hematoxylin–eosin stain, 200×. (b) Note poorly formed tubules containing mucinous material and spindle cells with eosinophilic cytoplasm and low-grade nuclei.
Hematoxylin–eosin stain, 200×. (c) Note psammoma bodies and foamy macrophages. Hematoxylin–eosin stain, 200×. (d) Note alcian blue positive stromal mucinous deposits.
Alcian blue stain, 200×.

Fig. 3. Mucinous tubular and spindle cell carcinoma (MTSCC). (a) Note positivity for racemase in tumor cells. P504s/AMACR, 200×. (b) Note positivity for RCC in tumor cells.
RCC, 200×. (c) Note positivity for CK7 in scattered tumor cells. CK7, 200×. (d) FISH with centromeric probes for chromosomes 7 (in red) and 17 (in green) in the tumor,
showing nuclei with two red and two green hybridization signals, consistent with the presence of a normal copy number for chromosomes 7 and 17. (For interpretation of
the references to color in this figure legend, the reader is referred to the web version of this article.)

Please cite this article in press as: B.A. Alexiev, et al., Mucinous tubular and spindle cell carcinoma of the kidney with prominent
papillary component, a non-classic morphologic variant. A histologic, immunohistochemical, electron microscopic and fluorescence
in situ hybridization study, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.002
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Table 1 Clear cell change and papillary architecture can become quite
Mucinous tubular and spindle cell carcinoma (MTSCC). Differential diagnostic
extensive in some tumors causing morphologic confusion with
considerations.c
clear cell papillary RCC, which occurs predominantly in kidneys
MTSCC PRCC CCPRCC Xp11TRCC with ESRD [3,8]. However, the characteristic nuclear positioning
Spindle cells Yes Yes Yesb No away from the basement membrane, lack of prominent spindled
Clear cells Yes Yes Yes Yes component and mucinous background, and distinct immunoprofile
Tubules Yes Yes Yes Yes (CK7+, vimentin+, cytokeratin 34betaE12+, RCC−, P504s/AMACR−)
True papillae Yes Yes Yes Yes
of clear cell papillary RCC should allow one to separate these two
Psammoma bodies Yes Yes No Yes
Macrophageal aggregates Yes Yes No Yes tumor types [3,8].
Stromal mucin Yes No No No Another differential diagnostic consideration is RCC with Xp11.2
Biologic aggressivenessa Yes Yes No Yes translocations [1]. Microscopically, the most distinctive and com-
Immunoprofile mon pattern is the presence of both clear cells and papillary
CK7 (+) (+) (+) (−) architecture. Nuclei tend to be high grade, in contrast to the low
P504s/AMACR (+) (+) (−) (+) nuclear grade of MTSCC. The most distinctive immunohistochem-
Cytokeratin 34betaE12 (−) (+/−) (+) (−)
ical feature of Xp11.2 translocation RCC, which is not present in
RCC (+) (+) (−) (+/−)
Vimentin (+) (+) (+) (+/−) MTSCC, is a strong nuclear staining for the TFE3 protein. Unlike
TFE3 (−) (−) (−) (+) MTSCC, Xp11.2 translocation RCC is a group of neoplasms defined
Genetics
by chromosomal translocations involving the TFE3 transcription
3p deletion (−) (−) (−) (−) factor gene located at the Xp11.2 locus [1].
VHL gene mutation (−) (−) (−) (−) The origin of MTSCC has been suggested as the loop of Henle or
Trisomy 7 and 17 (−) (+) (−) (−) collecting duct, but this view is controversial [10,12]. MTSCC in the
Xp11 translocations (−) (−) (−) (+)
current study expressed RCC, CD10 and P504s/AMACR (proximal
PRCC: papillary renal cell carcinoma; CCPRCC: clear cell papillary renal cell carci- nephron proteins) and was negative for kidney-specific cadherin
noma; Xp11TRCC: renal cell carcinoma with Xp11.2 translocations.
a
and cytokeratin 34betaE12 (distal convoluted tubule markers). The
High grade, necrosis, vascular and/or adipose tissue invasion, metastases.
b ultrastructural profile is not entirely indicative of the cellular origin
Low-grade spindle cells may be seen in areas with myoid metaplasia/renal
angiomyomatous tumor-like features. of the tumor.
c
References: [1–5]. Results of molecular genetic analysis showed multiple chromo-
somal losses and gains; there was no 3p loss, mutation in the VHL
gene or trisomy 7 and 17 in MTSCC [4,9]. Abnormalities of chro-
mosomes 15 and 22 suggest a diagnosis of MTSCC even in cases of
transitioned into a MTSCC-like morphology, exhibiting elongated high-grade tumors [9].
tubules with low-grade spindle cell areas in a background of muci- The patient in this study presented with low stage tumor,
nous stroma. Notably, the later was present in the papillary regions without recurrent disease or distant metastases, approximately 3
as well. months from the initial diagnosis. Rare cases with sarcomatoid
The differential diagnosis of MTSCC with unusual morphological dedifferentiation, nodal and liver metastases have been reported
features includes other lesions of the kidney that can have a pre- [13,15]. The follow-up data are limited and the full biologic poten-
dominantly papillary pattern of growth, clear cells, psammomatous tial of this tumor remains to be established.
calcifications and stromal macrophageal aggregates (Table 1). The Pathologists must be aware of the histologic spectrum (non-
major considerations are papillary RCC, clear cell papillary RCC, and classic variants) of MTSCC to ensure their accurate diagnosis.
Xp11.2 translocation carcinoma [1,3,8,14]. Cytogenetic analysis should be performed in difficult cases to avoid
MTSCC has been shown to have significant morphologic and misdiagnosis.
immunohistochemical overlap with papillary RCC, specifically, the
predominantly solid variant of the latter [2,14]. Both are circum-
scribed lesions featuring solid areas, tubules, low-grade spindle cell Conflict of interest
foci and focal papillary architecture. The stroma of both may con-
tain foamy macrophages and psammoma bodies. The key feature We declare that we have no conflict of interest.
discriminating between these two neoplasms is the characteristic
acidic stromal mucin deposition in MTSCC. However, mucin-poor
MTSCC variants have been reported [5]. At the immunohistochem- References
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Please cite this article in press as: B.A. Alexiev, et al., Mucinous tubular and spindle cell carcinoma of the kidney with prominent
papillary component, a non-classic morphologic variant. A histologic, immunohistochemical, electron microscopic and fluorescence
in situ hybridization study, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.002
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Please cite this article in press as: B.A. Alexiev, et al., Mucinous tubular and spindle cell carcinoma of the kidney with prominent
papillary component, a non-classic morphologic variant. A histologic, immunohistochemical, electron microscopic and fluorescence
in situ hybridization study, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.002