Primary Clear Cell Adenocarcinoma of the Colon: A Rare Oncologic Variant

A Case Report and Review of Related Literature

Submitted to the
Philippine Society of General Surgeons- Northern Luzon Chapter

Submitted by:
Laurence Owen R. Bundal, M.D.
First Year Resident, Department of General Surgery
Baguio General Hospital and Medical Center
Primary Author

Joey S. Lucas,MD,FPCS,FPSGS,FPSOSP
Training officer,Department of General Surgery

Honorio Ma. A. Pangilinan Jr.,MD,FPCS,FPALES,FACS

Chairman, Department of General Surgery

Abstract
Primary clear cell adenocarcinoma of the colon is a rare oncologic variant. Based from the
different publications it revealed 14 previously reported cases around the world. It usually
manifest in the kidney and within tissues of Müllerian system, and migrating from the colon is
unusual. Cases reported showed that it affects elderly men more commonly and usually appears
in the left side of the colon. From the available publication and references, there were no noted
report that have cited here in the Philippines. This may possibly be the 1st case to be presented in
the Philippines. These case report focuses on providing information regarding this rare type of
colon cancer. This is a case of 33-year-old man admitted at BGHMC with a chief complaint of
Abdominal pain. Laboratory work up was done which showed CT Scan findings of soft tissue
mass involving the ascending colon extending into the hepatic flexure. Patient eventually
underwent extended right hemicolectomy. Histopathologic finding showed the presence of clear
cell features in the colon. Patient was eventually discharged as a case of Ascending colon clear
cell carcinoma stage IIIC (T4aN2bM0). However, was lost to follow up. Immunohistochemistry
was not done and diagnose solely in the histopathologic findings. Due to limited information of
the case, No screening tests are currently recommended for detection of primary clear cell
adenocarcinoma, nor management of these disease. More research is needed, and should focus
on this malignancy, especially in regard to prognosis and in order to provide the best treatment
option.
 Introduction

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in

the country today. It is a multifactorial disease that encompasses environmental exposures

(including diet), genetic factors and inflammatory conditions of the digestive tract. Based from

the recent studies regarding cancer statistics, The Philippines rank as one of the lowest in terms

of age specific survival rates falling behind countries such as Japan, Thailand, India, Europe and

the United states. Despite the available screening programs, most Filipino cancer patients tends

to seek consult to the Doctors only when symptoms occurs or at an advanced stages. Hence,

there much action to be done for proper dissemination of cancer education and the

implementation of the different programs for cancer prevention. Adenocarcinomas make up of

about 95 percent of suspected colorectal cancer cases. This type of cancer develop in the cells of

the lining inside the colon and/or the rectum. They typically start as a growth of tissue called a

polyp. Different types of Adenocarcinoma would characterized based on its morphological

features such as mucinous adenocarcinoma, signet ring cell adenocarcinoma. One of the rare

type of colon adenocarcinoma is Clear cell adenocarcinoma of the colon and rectum.

Clear cell adenocarcinomas is a malignancy that usually manifest in the kidney and within

tissues of Müllerian system, such as the lower urinary and female genital tracts; So It is quite

unusual to present with these characteristics in the colon. The histologic features of clear cell

adenocarcinomas characterized as rounded or polygonal-shaped cells with well-defined cell

membranes and large amounts of clear or granular cytoplasm, typically attributed to abundant

cytoplasmic glycogen. The first reported case of primary clear cell adenocarcinoma of the colon

was published in 1964. Even though advances have been made in the techniques regarding
pathological examinations and immunohistochemistry over the past years, this tumor has been

rarely diagnosed in the colon.

CASE REPORT

Patient is a 33 year old male who was admitted at BGHMC with the chief complaint of

abdominal pain. Patient presented with 6 months history of intermittent abdominal pain which

was described as vague, colicky in character (5/10). It was also associated with persistent episode

of weakness, early satiety and loss of appetite. Patient denied any episode of nausea,vomiting,

diarrhea, constipation nor presence of melena nor hematochezia. Patient claimed to notice a

palpable ,firm movable, nonpainful mass at right side of abdomen . No Consult was done. No

Medications were taken. One month prior consult, Patient still presented with previous

symptoms. Patient eventually sought consult at these institution wherein colonoscopy and biopsy

was done whish showed “Chronic non specific colitis with lymphoid aggregates”. However

Patient was then lost to follow up. Due to persistence of abdominal pain and body weakness

,patient was eventually admitted. Physical Examination revealed unremarkable vitals sign .The

Abdomen was flat, globular , nondistended with noted 6x 6 cm intrabdominal mass at right side

of the abdomen. His past medical history and past surgical history or allergies was

unremarkable. He denied any tobacco or illicit drug use but a social history review was positive

for occasional alcoholic beverage. There are no noted family history of cancer in the family.

Patient was then admitted as a case of Intraabdominal mass with colonic extension.

A complete Laboratory work-up were done which showed presence of anemia with decreasing

value of Hemoglobin(34 g/L) , Hematocrit (0.10 L/L) and Multiple Electrolyte Imbalance

Hyponatremic, (Na:135 umol/L ), (K:3.4 umol/L), (Cl:94) umol/L . Patient eventually

underwent correction of Anemia and Electrolyte Imbalance. A carcinoembryonic antigen (CEA)

level was normal (0.50 ng/ml). A CT Scan of the abdomen (Fig.1) reveal a large lobulated

heterogeneously enhancing soft tissue mass density with central low density area of necrosis and

gas densities involving the ascending colon extending into the hepatic flexure with concomitant

luminal narrowing . The mass exhibit exophytic growth and approximately measures

11.5x13.8x12.5 cm. Perilesional collateral vessels and multiple enlarged lymph node with central

hypodense necrotic portions are seen, the largest of which measures 3.4x 3.0 cm noted in the

right lower paracolic gutter.

He underwent an exploratory laparotomy with extended right hemicolectomy. Intraoperative

findings (Fig.2) showed massive ascites with noted 15x20 cm mesenteric mass involving the

cecum and ascending colon. Multiple enlarged lymph nodes were also noted. Specimen was sent

to the Pathology department and Histopathologic diagnosis (Fig.3,4) showed poorly

differentiated malignancy with Clear cell features, Colon extending to the pericolonic fat. 18 out

of 21 pericolonic lymph nodes are positive for metastasis. Microscopic description showed

tumor cells arranged in sheets , solid nests, tubules and papillary formation . These cells exhibit

moderate to markedly enlarged , pleomorphic and hyperchromatic to vesicular nuclei with

prominent nucleoli and clear cytoplasm. Patient was eventually send home after few days post-

op with no complication. However, Patient was lost to follow up .

 Discussion

The presence of clear cell change in colorectal adenoma and adenocarcinoma is extremely rare.

14 cases have been documented in English-language publications, The last reported case was last

2011. Based from the gathered information. In a study involving 3,486 cases of different types

of colon cancer, only 0.086% had clear cell changes.2 The average age of these patients was 62

years (Table 1). More male patients with clear cell adenocarcinoma of the colorectum have been

reported, and the tumor tends to be located on the left side. In comparison to the patient’s case,

it is not only rare in occurrence, but also in early age of onset and location.

Clear cell feature can be found within tissues of Müllerian system derivation, such as the lower

urinary and female genital tracts; other less common sites include the larynx, breast, pancreas,

stomach, biliary system, and colon. Morphological features of the colon shows the intestinal

epithelium is the layer of cells which composed of simple columnar epithelium. The histologic

features of clear cell adenocarcinomas presents with rounded or polygonal-shaped cells with

well-defined cell membranes and large amounts of clear or granular cytoplasm, typically

attributed to abundant cytoplasmic glycogen. Morphologically, primary colonic clear cell

adenocarcinoma shares traits with the more common clear cell malignancies of the uterus,

kidney, and ovaries. It was necessary to distinguish primary clear cell adenocarcinoma of the

colon from colonic metastasis of clear cell adenocarcinoma deriving from the ovary, kidney, and

other organs. Based from the results of the computed tomography examination of the patient’s

whole body, showed no evidence of a tumor other than in the colon .

Immunohistochemistry is crucial for establishing the origin of different neoplastic cells. The

typical immunohistochemical profile for adenocarcinomas derived within the colon is strong
expression of CK20 without expression of CK7. Studies have demonstrated a strong staining

with CK7 but only focal positivity with CK20 for patient diagnosed as a case of Clear cell

adecarcinoma..Unfortunately, since our patient was lost to follow up. Immunostaining was noted

done. Hence this report rely on the histopathologic finding of clear cell adenocarcinoma

As shown in Table 1, Prognosis and outcome is difficult to establish given the rareness of

reported cases. Seven cases have unknown survival information. Two cases report no

reoccurrence at one-year follow-up without further information. 4 Outcomes from the remaining

five cases, have a mean survival of 10.2 months from diagnosis, suggesting this variant to be an

aggressive cancer. Lymph node metastasis was reported in a total of five cases, including ours.

Most patients underwent surgical therapy, even in advanced age. Unfortunately, little is known

about the incidence and prognosis of primary colonic clear cell adenocarcinoma given the

paucity of reported cases. No screening genetic analysis tests are currently recommended for

detection of primary clear cell adenocarcinoma, a rare entity. In conclusion, we diagnosed our

patient histopathologically as having clear cell adenocarcinoma of the colon.

Conclusion

In conclusion, we diagnosed our patient histopathologically as having clear cell adenocarcinoma

of the colon. Immunohistochemistry is important for establishing the origin of these neoplastic

cells .More information and research about this malignancy is needed, especially in regard to

prognosis and outcome in order to provide the best treatment option for this type of rare disea
Appendices
Table 1. Summary of Reported cases of Clear Cell Adenocarcinoma of the Colon and Rectum
Reference:

1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan
2.World Health Organization, International Agency for Research on Cancer. Colorectal Cancer:
Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. International Agency
for Research on Cancer.
3. DomotoH,Terahata.S,Senoh Aet al. Clear cell changes in colorectal adenomas: Its incidents
and histological characteristics.
4. Clear Cell Adenocarcinoma With Enteroblastic Differentiation of the Ascending Colon.
Journal of Clinical Oncology , Volume 29, August 1 2011
5. Clear cell adenocarcinoma of the colon: A case report and review of literature, World Journal
of Gastroenterology 2008 February 21;
6. Primary clear cell adenocarcinoma of the colon: a case report and review, The Journal of the
Louisiana State Medical Society: official organ of the Louisiana State Medical Society July 2014