Renal carcinoid tumor with liver metastasis followed up postoperatively for 9 years
Ouyang et al. Diagnostic Pathology
Renal carcinoid tumor with liver metastasis followed up postoperatively for 9 years
BinShen Ouyang 0
XiaoMei Ma 0
HongZhu Yan 0
Jin He 0
ChunYan Xia 0
HongYu Yu 0
0 Department of Pathology, Shanghai Chang Zheng Hospital, The Second Military Medical University , Shanghai , China
Background: We describe a case of renal carcinoid tumor with liver metastasis followed up postoperatively for 9 years. Case presentation: A 33-year-old man presented with left flank dull ache. On the abdominal computed tomography, a solid renal mass in the upper portion of the left kidney was detected. The patient had no other abnormal findings, such as suspected distant metastasis or lymph node metastasis. Radical nephrectomy was performed on 14/9/2005. Histological examination and immunohistochemical staining confirm primary renal carcinoid tumor. 9 years after radical nephrectomy, computed tomography of the abdomen demonstrated a 2 cm × 1.8 cm cyst mass in the right liver. Similar pathologic characteristics were found between the renal carcinoid tumor and liver tumor. Conclusions: We present a primary renal carcinoid tumor with liver metastasis 9 years after radical nephrectomy. With literature review, renal carcinoid tumors exhibit heterogenous behavior.
Kidney; Carcinoid; Metastasis
Carcinoid tumors of the kidney are extremely uncommon.
Primary carcinoid tumors of the kidney are low-grade,
malignant tumors that arise from neuroendocrine cells.
Since then, no more than 100 cases have been reported
in the literature, and approximately 20 cases developed
liver metastases at the time of initial diagnosis [1–3].
Only two cases were found liver metastases 5 and
6 months after surgery [1, 4]. Herein, we present the
case of a 33-years-old man who had primary renal
carcinoid with liver metastasis followed up after radical
nephrectomy for 9 years. Histological examination and
immunohistochemical staining confirm consistent
characteristics between liver and renal tumor.
A 33-year-old man presented with left flank dull ache. On
the abdominal computed tomography, a solid renal mass
in the upper portion of the left kidney was identified.
The mass was measured 2.8 cm × 2.8 cm × 2.5 cm in
size, was well-defined. The patient had no other
abnormal findings, such as suspected distant metastasis
or lymph node metastasis. Radical nephrectomy was
performed on 14/9/2005. On gross examination, the
nephrectomy specimen measured 11.5 cm × 6.5 cm ×
4.5 cm and the tumor was a solid, grayish-brown mass
measured 3.5 cm × 2.5 cm × 2.2 cm in size. Histologic
examination demonstrated trabecular and ribbonlike
patterns with minimal fibrotic stroma. The cytoplasm
was granular and eosinophilic with uniform round to
oval nuclei with finely stippled chromatin and
inconspicuous nucleoli. Mitoses were not found (0 per 10
high-power fields) on H&E stain. The final pathologic
examination revealed a well-differentiated
neuroendocrine (carcinoid) tumor confined to the kidney (Fig. 1).
Immunohistochemical stains demonstrated labeling with
chromogranin, neuron-specific enolase and synaptophysin
(Fig. 2), and the proliferation index was less than 2 % as
measured by immunohistochemistry for Ki-67. Further
radiation and chemotherapy were not received.
Nine years after radical nephrectomy, computed
tomography of the abdomen demonstrated a 2 cm × 1.8 cm
cyst mass in the right liver and multiple high density
shadow in gallbladder. No enlarged lymph nodes were
found in the abdominal cavity. Cholecystectomy and
extirpation for hepatic cyst were performed by laparoscopy
surgery. Histologic examination demonstrated trabecular
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Fig. 1 Tightly packed trabecular and glandular formations in renal
carcinoid tumor with minimal stroma (left side of image), ill-defined
with peripheral nephridial tissue(right side of image) (H&E × 200)
and glandlike growth (Fig. 3), moderate and uniform
nuclei and mitoses weren't found (0 per 10 high-power
fields). Advanced immunohistochemistry revealed that the
lesion was positive for synaptophysin (Fig. 4) and CD56,
but negative for chromogranin and neuron-specific
enolase. These features are supported in a neuroendocrine
tumor. Due to the similar pathologic characteristics
between the primary renal carcinoid tumor and liver tumor.
The final pathology report indicated a carcinoid tumor of
the left kidney with liver metastasis.
Carcinoid tumors occur most commonly in the
gastrointestinal tract and respiratory tract. Primary renal
carcinoid tumors are exceedingly rare and since the
first reported case in 1966, less than 100 cases have
been reported in the literature. Due to a small number of
cases, biological behavior of these tumors is undetermined.
Fig. 3 Renal carcinoid tumor with liver metastasis, tumor cells are
arranged in trabecular and glandlike appearance (H&E × 200)
Although the majority of patients in previous reports were
diagnosed with either local or distant metastatic disease at
the time of initial diagnosis, most patients were
asymptomatic and demonstrated prolonged survival. The most
common site for metastatic is regional lymph nodes, other
locations include liver [1, 5], bone [6, 7] and lung . The
previous literature report liver metastatic disease at the
time of surgery, only two patients developed liver
metastases within 5 and 6 months of surgery [1, 4]. This is the rare
case reported liver metastasis followed up after radical
nephrectomy for 9 years.
The cell of origin of renal carcinoid tumors has not been
determined. It seems that the tumor is not arise in the
kidney and perhaps originate from scattered neuroendocrine
cells derived from acquired or congenital abnormalities,
because no neuroendocrine cell was detected within the
renal parenchyma or hilum  and renal carcinoid tumors
showed absence of reactivity with PAX-2 and PAX-8 .
The two markers have been shown to be associated with
Fig. 2 Intense cytoplasmic reactivity for synaptophysin (×400)
Fig. 4 Intense cytoplasmic reactivity for synaptophysin (×400)
the developing mesonephric tissue and may serve as
immunohistochemical markers of renal tumors. The
predominant histologic pattern of the tumor includes tightly
packed cords with minimal stroma, trabecular growth
with prominent stroma, focal solid nests of cell or focal
glandular lumina, other more rare histopathologic features
were calcification and lymphocytic infiltrates. In our case,
both kidney and liver lesion histologically show trabecular
and glandlike appearance, moderate and uniform nuclei
with finely stippled chromatin, but the later lack ribbon
patterns. Mitoses and necrosis weren’t found.
Immunohistochemical stains suggest that
neuroendocrine markers synaptophysin, chromogranin and CD56
were positive in both lesions, TTF-1, WT-1 and CDX-2
were negative . It’s interesting that immunostaining
of chromogranin was at least focal positive in kidney
lesion, but negative in liver lesion. We are not well
understood. It is speculated that protein expression of
chromogranin and neuron-specific enolase was changed
during the period of liver metastasis. It should be noticed
that the relatively low specificity of neuron-specific
enolase as a neural marker, because neuron-specific enolase
immunostaining is observed in the normal kidney at the
level of distal/medullary tubules, and in a high percentage
of renal cell neoplasms .
The differential diagnosis of renal carcinoid tumor
includes small cell carcinoma, primitive neuroectodermal
tumor(PNET), neuroblastoma, paraganglioma,
metanephric adenomas. In contrast to small cell carcinoma, renal
carcinoid tumors lack a brisk mitotic rate, apoptotic
activity, nuclear molding, necrosis and high
proliferation indices. Furthermore, most small cell carcinomas
lack the typical organized architecture that is
distinctive for the carcinoid tumor . Both PNET and renal
carcinoid tumor can demonstrate solid areas and
regions of rosettelike structures, although unlike renal
carcinoids, PENT is strong immunoreactivity for
CD99 and have the t(11; 22)(q24; q12) translocation
with the fusion transcript between the EWSR1
gene(22q12) and the FLI gene(11q24) .
Paragangliomas and neuroblastomas arising in kidneys are
exceedingly rare, although both can mimic renal
carcinoid. Paragangliomas more commonly contain a
nested pattern of neuroendocrine cells with granular
basophilic cytoplasm surrounded by S100 positive
sustentacular cells. Neuroblastoma contain
HomerWright rosettes, neurofibrillary stroma which were not
found in renal carcinoid tumors. Metanephric
adenomas and renal carcinoid tumors are both composed
of tightly packed small, monotonous cells with
uniform nuclei and inconspicuous nucleoli. In contrast to
renal carcinoid tumor, metanephric adenomas have
round acini with embrynal appearance and psammoma
bodies were commonly seen. Furthermore, metanephric
adenomas lack immunoreactivity for neuroendocrine
markers such as synaptophysin, chromogranin, and CD56.
Radical nephrectomy is the gold standard treatment for
renal carcinoid, partial nephrectomy is a good alternative
regarding the location and diameter of the tumor. Other
neo/adjuvant treatment, such as chemotherapy,
sandostatin, targeted therapy, radiotherapy or local lymph node
dissection, but no trial has shown its direct impact on
Neuroendocrine tumors (NET) commonly express
serum somatostatin receptors as determined using
somatostatin receptor scintigraphy with radiolabeled form of
somatostatin analog octreotide. Octreotide not only plays
an important role in decreasing the symptoms of
hormonal excess but is considered a first-line antineoplastic
systemic therapy for patients with a positive octreoscan .
Octreotide may have activity against primary or metastatic
renal carcinoid . In our case, octreotide have not been
used postoperatively. There need more clinical trials to
evaluate the effect of octreotide.
The prognosis of renal carcinoid tumors is not
predictable because of their rarity. The majority of cases did not
present evidence of disease after treatment. According to
2010 WHO classification and grading system, 6 previously
reported cases of renal carcinoid tumor should be
classified as renal neuroendocrine tumor grade 2 (mitotic
activity 2–20/10 high-power fields and/or 3–20 % Ki-67 index
level) [1, 15, 16]. These patients seem to be with a worse
prognosis, because 5 of 6 renal NET grade 2 cases
previously reported had metastasis and 2 of 6 patients died
Renal carcinoid tumors exhibit heterogenous behavior.
Although it seems that no good prognostic factors to
predict the outcome of patients, Ki-67 index level and
mitotic rate might be useful to aid pathologists and
clinicians in trying to predict the outcome of a similar case.
Written informed consent was obtained from the patient
for publication of this case report and any accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
BSO drafted the report, contributed to concept. HYY and XMM contributed to
concept and design. JH carried out the immunoassays. HZY and CYX helped to
draft the manuscript. All authors approved the final version of the manuscript.
1. Hansel DE , Epstein JI , Berbescu E , Fine SW , Young RH , Cheville JC . Renal carcinoid tumor: a clinicopathologic study of 21 cases . Am J Surg Pathol . 2007 ; 31 ( 10 ): 1539 - 44 .
2. Jeung JA , Cao D , Selli BW , Clapp WL , Oliai BR , Parwani AV , et al. Primary renal carcinoid tumors: clinicopathologic features of 9 cases with emphasis on novel immunohistochemical findings . Hum Pathol . 2011 ; 42 ( 10 ): 1554 - 61 .
3. Gedaly R , Jeon H , Johnston TD , McHugh PP , Rowland RG , Ranjan D. Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis . World J Surg Oncol . 2008 ; 6 : 41 .
4. Rodriguez-Covarrubias F , Gomez X , Valerio JC , Lome-Maldonado C , Gabilondo F. Carcinoid tumor arising in a horseshoe kidney . Int Urol Nephrol . 2007 ; 39 ( 2 ): 373 - 6 .
5. Kurl S , Rytkonen H , Farin P , Ala-Opas M , Soimakallio S. A primary carcinoid tumor of the kidney: a case report and review of the literature . Abdom Imaging . 1996 ; 21 ( 5 ): 464 - 7 .
6. Chiang MC , Ou YC , Yang CR , Cheng CL , Ho HC . Primary renal carcinoid tumor with multiple metastases . J Chin Med Assoc . 2010 ; 73 ( 8 ): 435 - 7 .
7. Lim KH , Huang MJ , Yang S , Hsieh RK , Lin J. Primary carcinoid tumor of prostate presenting with bone marrow metastases . Urology . 2005 ; 65 ( 1 ): 174 .
8. Guy L , Begin LR , Oligny LL , Brock GB , Chevalier S , Aprikian AG. Searching for an intrinsic neuroendocrine cell in the kidney . An immunohistochemical study of the fetal, infantile and adult kidney . Pathol Res Pract . 1999 ; 195 ( 1 ): 25 - 30 .
9. Tong GX , Yu WM , Beaubier NT , Weeden EM , Hamele-Bena D , Mansukhani MM , et al. Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study . Mod Pathol . 2009 ; 22 ( 9 ): 1218 - 27 .
10. Romero FR , Rais-Bahrami S , Permpongkosol S , Fine SW , Kohanim S , Jarrett TW. Primary carcinoid tumors of the kidney . J Urol . 2006 ; 176 ( 6 Pt 1 ): 2359 - 66 .
11. Aung PP , Killian K , Poropatich CO , Linehan WM , Merino MJ . Primary neuroendocrine tumors of the kidney: morphological and molecular alterations of an uncommon malignancy . Hum Pathol . 2013 ; 44 ( 5 ): 873 - 80 .
12. Tetu B , Ro JY , Ayala AG , Ordonez NG , Johnson DE . Small cell carcinoma of the kidney: a clinicopathologic, immunohistochemical, and ultrastructural study . Cancer . 1987 ; 60 ( 8 ): 1809 - 14 .
13. Karpate A , Menon S , Basak R , Yuvaraja TB , Tongaonkar HB , Desai SB . Ewing sarcoma/primitive neuroectodermal tumor of the kidney: clinicopathologic analysis of 34 cases . Ann Diagn Pathol . 2012 ; 16 ( 4 ): 267 - 74 .
14. Rinke A , Muller HH , Schade-Brittinger C , Klose KJ , Barth P , Wied M , et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group . J Clin Oncol . 2009 ; 27 ( 28 ): 4656 - 63 .
15. Tanaka T , Yamamoto H , Imai A , Shingo H , Yoneyama T , Koie T , et al. A case of primary renal carcinoid tumor . Case Rep Urol . 2015 ; 2015 : 736213 .
16. Korkmaz T , Seber S , Yavuzer D , Gumus M , Turhal NS . Primary renal carcinoid: treatment and prognosis . Crit Rev Oncol Hematol . 2013 ; 87 ( 3 ): 256 - 64 .