3.
Abbreviations
AJCC : American Joint Committee on Cancer
CRC : Colorectal Cancer
CT : Computed Tomography
H.E. : Hematoxylin-eosin
MSI : Microsatellite Instability
NAACCR : North
American Association of Central Cancer Registries
PET : Positron Emission Tomography
RCC : Renal Cell Carcinoma
TTM : Tumor-to-Tumor Metastasis
4.
Introduction
Synchronous
multiple primary tumors are relatively rare. It has been hypothesized that
concurrent tumors can arise from tissues with similar embryological origin when
they are simultaneously affected by environmental factors. Accumulated data
show an infrequent yet strong association of the urogenital and
gastrointestinal tumors as most common pairing of synchronous primary cancers [1,2]. Tumor-To-Tumor Metastasis (TTM) is an uncommon
phenomenon explained as a metastasis in a histologically separate tumor [3,4]. We present a case of clinically and
pathologically documented synchronous double malignant tumors of the colon and
kidney, meanwhile tumor to tumor metastasis from colon to kidney. To the best
of our knowledge, no case with such a concurrency has been reported to date in
the literature.
5.
Case reports
5.1.
Case presentation
A
49-year-old male presented with a chief complaint of abdominal pain. Patient
reported a recent change in his bowel habit. His medical history was
significant for smoking and obesity with no family history of malignancies. He
previously underwent sleeve gastrectomy in 2014 and reported 100 lbs. weight
loss since then.
Abdominal
Computed Tomography (CT) (Figure 1 and 2) showed
generalized sigmoid colon wall thickening and luminal narrowing suggestive of
the annular constricting lesion and several hepatic lesions concerning for
metastatic disease. The CT scan also revealed an exophytic complex mass arising
from the upper pole of the left kidney, suggestive of Renal Cell Carcinoma (RCC).
The patient
underwent an endoscopic examination and was biopsied for histological
definition. Histological diagnosis of the colon biopsy confirmed the presence
of tubular adenoma with intramucosal adeno carcinoma. The staging Positron
Emission Tomography (PET) scan was consistent with the primary diagnosis. A
CT-guided biopsy of the right liver and left kidney was performed. Both
Histologic and immunophenotypic profiles (positive for CK20 and CDX2, negative
for CK7) of the liver lesion supported a diagnosis of metastatic adenocarcinoma
of colon as the primary origin. However, the tumor cells morphology and
immunoprofile of the left kidney mass were most compatible with renal cell
carcinoma. After careful review of the findings, a multidisciplinary surgical
approach was planned. Following neoadjuvant chemotherapy, the patient underwent
simultaneous lower anterior resection of the recto sigmoid colon and left
radical nephrectomy. He had an uneventful and favorable postoperative course
and was transferred back to the oncology division afterward.
5.2.
Gross Pathology
Both
radical nephrectomy and sigmoid colon specimens were obtained by our department
of pathology for histopathological examination. The radical nephrectomy
specimen composed of left kidney, ureter stump and perinephric tissue. Grossly
a well-circumscribed, solitary mass (3.5 x 2.5 x 2.5 cm) involving the upper
pole of the left kidney was recognized. The tumor was tan-yellow with focal
areas of hemorrhage. The renal sinus or the Gerota's fascia was not involved by
the tumor. A gray flat lesion (5 x 4.5 x 4 cm) with velvety granular surface
adjacent to a polyp (2 x 1.5 x 0.7 cm) was identified in the colon.
Macroscopically the tumor seemed to extend through the colonic wall.
5.3.
Microscopic Features
The
microscopic features are illustrated in (Figure 3).
All tissue samples were routinely fixed in 10 % formalin and embedded in
paraffin. Hematoxylin-Eosin (H.E.) and immunohistochemical stains were
performed. Microscopic examination of the colon revealed a tumor invading
through the muscularis propria, consisting of poorly differentiated glands
surrounded by desmoplastic reaction. The carcinomatous glands were lined by
tall columnar cells and their lamina showed frequent dirty necrosis. The tumor
cells expressed CK20 and CDX2 in accordance with the diagnosis of colorectal
adenocarcinoma.
Metastatic
carcinoma involving five of twelve resected peri-colonic lymph nodes was noted,
giving a final American Joint Committee on Cancer (AJCC) tumor stage of T3 N2a
M1b. Histological analysis of the left kidney revealed a renal cell carcinoma,
with compact alveolar architecture and sharply outlined boundaries. The nests were
composed of neoplastic cells with abundant clear cytoplasm and high nuclear
grade. Several areas of atypical spindle cells having marked nuclear
pleomorphism as well as rhomboid differentiation were identified. To our
surprise, a morphologically distinct area was found mostly circumscribed by the
RCC, showing glandular structure similar to the colorectal carcinoma. Immunohistochemical
staining was performed. The clear cell component exhibited vimentin, RCC and
PAX8 and was focally positive for CD10. The metastatic component was positive
for CK20 and CDX2 and negative for RCC, PAX-8 and vimentin. These findings
strongly evinced a colonic origin for metastatic tumor. A diagnosis of clear
cell renal cell carcinoma, histologic grade of four with both sarcomatoid and
rhabdoid features was then established. Also tumor revealed features compatible
with tumor to tumor metastasis of rectal adenocarcinoma to renal cell carcinoma.
The following genetic studies were done: K-RAS, N-RAS, and BRAF mutation, EGFR
amplifications and microsatellite instability tests were performed, but all
were found to be negative.
6.
Conclusions
This is
the first reported case of coinciding synchronous malignant tumors of the colon
and kidney with tumor-to-tumor metastasis from the colon to the kidney.
7.
Discussion
Coexistence
of two or more primary neoplasms in the same patient is an unusual but well
documented occurrence. The North American Association of Central Cancer
Registries (NAACCR) classifies double primary malignancies into two categories.
Synchronous malignancies are secondary tumors occurring either simultaneously
or within 2 months of the first malignancy. However, metachronous malignancies
are secondary tumors that develop at least 2 months after the first malignancy [5]. The current criteria by Warren and Gates are used
to identify synchronous tumors: each tumor must be malignant, each must be
distinct, and the possibility that one is a metastasis of the other must be
excluded [6]. Colorectal cancer (CRC) is the
fourth common cancer in the United States [7].
It has been suggested that patients with CRC have increased risk for developing
a second cancer [8]. In comparison to CRC, Renal
cell carcinoma occurs less frequently with an incidence of 61,816 new cases per
year [7]. The risk of multiple primary cancers
is higher in patients with kidney and renal pelvis cancers [9]. In particular, RCC has been the focus of many
studies within the past decade since it is associated with other primary
malignancies including breast, genitourinary, colorectal cancers and
non-Hodgkin's lymphoma [10-12].
Although
these tumors are individually common, the incidence of synchronous neoplasms of
the colon and kidney is rare [12]. Capra et al. [13] reported synchronous RCC in 0.4% of patients with
primary colorectal carcinoma. This concurrency is reported 0.5 % by O’Boyle and
Kemeny, [14] and 4.85% by Halak et al. [12]. However, autopsy series do not distinguish
between synchronous and metachronous tumors. Calderwood et al reported higher
risk of renal parenchymal tumors in patients diagnosed with CRC before age of
60 years [2]. Although the etiology of
synchronous primary malignancies is not fully understood, the results of this
cohort analysis supported possible shared environmental and genetic risk
factors between CRC and urologic cancers. Any benign or malignant tumor can be
a recipient of metastasis. While slowly increasing, it is still uncommon to
have metastasis from tumor-to-tumor. Renal cell carcinoma is the most common
recipient for tumor-to-tumor metastasis [10,15].
Among the donor tumors, lung cancer is the most frequent primary, followed by
breast cancer [16,17]. The higher stage of the
primary non-renal malignancies is correlated with the higher rate of metastasis
to kidney [18,19].
Renal
metastasis from the primary colon adenocarcinoma is rare [20]. It only accounts for less than 3% of all
secondary renal neoplasm’s based on historical postmortem analysis [16]. A
recent study at MD Anderson revealed that primary colorectal tumors comprise
10.6% of metastatic tumors to the kidney [20].
To the best of our knowledge, no case with a concurrency of these synchronous
tumors with tumor-to-tumor metastasis at the time of diagnosis has been
reported to date in the literature. We used the keywords “tumor-to-tumor
metastasis” and “synchronous tumors” in PubMed to perform an English literature
review of combined and separate publications of these entities, to date no case
has been reported. Tumor-to-tumor metastasis must be differentiated from a
collision tumor. In the literature, the two terms have frequently been used
interchangeably. Collision tumor is defined as two adjacent but histologically
distinct tumors in the same organ without any histological intermixing [21,22]. Campbell et al established the following
criteria for the diagnosis of TTM:
1) At
least two primary tumors must be present; 2) The recipient tumor must be a true
neoplasm; 3) The metastasis has to demonstrate real growth in the recipient
tumor, not simply contiguous invasion or non-adherent tumor emboli; 4) Metastases
into lymphoid tissue involved by hematopoietic neoplasms do not count [23,24]. Our case met all of the above criteria and
considered a true TTM.
There
has been much debate about why certain tumors are more likely to be donors or
recipients. The “seed and soil” theory by Paget’s, proposes that metastatic
tumor cells (seeds) have better development in a more favorable biochemical
microenvironment (soil) [25]. The “mechanical”
theory suggests that due to high blood flow, highly vascular architecture, and
anatomical location, the recipient tumors could be prone to metastases [26]. Individual characteristics of these tumors have
been described by several hypotheses. Indolent nature of RCC, its rich
vascularity and high glycogen/lipid content provides a proper environment for
tumor growth and it would explain why renal carcinoma is the most frequently
described recipient for TTM3, [15,27,28]. The
colon is drained by the portal venous system, thus CRC spreads through the
lymphatic and venous systems to local or distant organs. Although the liver is
by far the most common involved organ, CRC can metastasize to the brain, spleen
and kidney [17].
Both
tumor-to-tumor metastasis and synchronous primary tumors are infrequent
phenomena; Recognition of these incidents is important to avoid an incorrect
diagnosis as well as to provide an appropriate management. In the present case,
both colon and renal tumors were identified concurrently. Renal biopsy was done
to determine the treatment plan. Simultaneous hand-assisted laparoscopic
removal of both primary tumors was performed. With improvements in medical
imaging, early diagnosis of the silent RCC is possible during discovering
another cancer. Coexistence of renal mass in a patient with non-renal
malignancy is more likely to be an incidental primary renal tumor [18], however
high degree of suspicion should be employed to exclude metastasis. Additional
studies are needed to further improve our understanding of both synchronous
tumors and TTM in order to achieve the most optimal management for these
patients.
8.
Acknowledgements
None
9.
Conflict of interest
All
authors declare that they have no conflict of interest.
10.
Funding
None
Figure 1: CT scan of the
abdomen and pelvis. Annular constricting lesion involving sigmoid colon.
Figure 2: Staging CT shows
partially exophytic complex mass in the upper pole of the left kidney, 4.7 cm,
suggestive of renal cell carcinoma.
Figure 3: a: Clear cell renal cell carcinoma
containing metastatic deposit of colorectal carcinoma (H.E. x 20), b: Renal Cell Carcinoma with
sarcomatoid features (H.E. x 100), c: Renal
Cell Carcinoma with rhabdoid features (H.E. x 200), d: Tumor histology of poorly differentiated adenocarcinoma of colon
(H.E. x 200), e: Positive
immunoreactivity for RCC by clear cell carcinoma nests (x 40), f: The colon adenocarcinoma is strongly
positive for CK20 while the renal cell carcinoma is negative. (x 40).
case report