We report a case of synchronous primary colonic adenocarcinoma and malignant mesothelioma. A 61-year-old male presented with a six-month history of fatigue and weight loss. An abdominal computed tomography (CT) scan showed a 5.8 cm partially obstructing mass in the cecum with ascites and peritoneal thickening. A biopsy of the large mass showed an adenocarcinoma. Because the patient was clinically thought to be a T4 colon carcinoma with peritoneal metastatic lesions (M1), prior to initiating chemotherapy, a debulking right hemicolectomy was performed. Resection of the colon and ileum revealed a T3N0 colonic mucinous adenocarcinoma and concurrent diffuse malignant peritoneal mesothelioma. Presenting synchronous colonic and peritoneal mesothelial primary malignancies are exceedingly rare but must be considered to prevent incorrect clinical staging.
There are 102,480 new cases of colon cancer diagnosed every year in the United States. Approximately 50,830 patients die of colorectal cancer, accounting for 9% of all cancer death [
A 61-year-old man presented with a two-year history of worsening diarrhea, six months of fatigue, and weight loss. He had a 3-week history of abdominal pain. His past medical history was significant for coronary artery disease, hypertension, mitral valve repair, congestive heart failure, chronic obstructive pulmonary disease, and 40 pack year tobacco abuse. He was a Navy Veteran with an unknown service record. He was a retired quality control factory worker who at one time worked in construction. Although all factors could have had potential exposure to asbestos, he did not have a clear documented source of exposure to asbestos. He had a positive fecal occult blood test. Colonoscopy revealed a 5 cm circumferential mass in the ascending colon at the hepatic flexure consistent with a primary malignancy. A subsequent endoscopic biopsy of the mass revealed an adenocarcinoma arising in a tubulovillous adenoma. An abdominal computed tomography (CT) scan showed a 5.8 cm partially obstructing cecal mass (Figure
Abdominal imaging. (a) Computed tomography and (b) positron emission tomography scans showed a 5.8 cm partially obstructing cecal mass (arrow) with ascites and peritoneal thickening.
Since he developed obstructive symptoms two months after his initial presentation and at the recommendation of his treating Oncologist, a palliative hand-assisted laparoscopic right hemicolectomy was performed in order to decrease the tumor burden to optimize the effects of his planned chemotherapy treatments. During the procedure, diffuse peritoneal implants thought to be consistent with suspected carcinomatosis were identified by the surgeon and approximately 800 mL of thick peritoneal fluid was evacuated. The patient tolerated the procedure without any overt complications. After his final diagnosis, he was offered chemotherapy for his colonic adenocarcinoma and unsuspected mesothelioma, but, with his unsure prognosis related to his mesothelioma, he declined further treatments. He chose to transfer his care to another facility. In follow-up, he continues to suffer from massive ascites with periodic therapeutic paracentesis but is alive at 56 months since his diagnosis.
The right hemicolectomy specimen consisted of a segment of right colon and terminal ileum with attached appendix and separate portion of omentum. In the colonic mucosa, 7.2 cm from ileocecal valve and 13.4 cm from distal margin, there was a tan-red to pink polypoid, nearly circumferential mass, which measured 6.5 × 5.3 × 4.9 cm. On cross section, the mass was tan-white and friable with a mucinous appearance. The mass extended through the underlying muscularis propria to the serosa and surrounding mesenteric adipose tissues. Overlying the external surface of the mass, there was a tan-red area of serosal puckering which measured 1.5 × 1.5 cm. The remainder of the serosa of ileum (including the proximal margin), appendix and colon serosa, and surrounding mesenteric adipose tissues was diffusely red, gritty, and scabrous with small nodules ranging from 0.2 cm to 0.6 cm. These multiple lesions were presumed to represent serosal metastases from the adenocarcinoma. Within the attached mesenteric fat, there were multiple tan-pink, rubbery lymph nodes ranging from 0.2 cm to 0.7 cm. The omentum was very abnormal and showed a “bumpy,” tan to yellow nodular appearance.
Microscopic sections of the colonic mass showed a full thickness infiltrating adenocarcinoma comprised predominantly of irregularly infiltrating fused glands with focal tubular structures and small individual cell clusters. There was a mucinous adenocarcinoma component with large lakes of extracellular mucin and suspended tumor glands. This pattern comprised more than 50% of the tumor (Figures
Histopathology of tumors. (a) Malignant mesothelioma (left) and adenocarcinoma in mucin pool (right). (b) Adenocarcinoma with atypical glands. (c) Mesothelioma showing psammoma bodies (arrows) and papilla with fibrovascular cores. (d) Mesothelioma demonstrating tubuloglandular structures.
Examination of the grossly visible serosal gritty areas with nodules showed a completely different pattern from the colonic mucinous adenocarcinoma. The cells resembled mesothelial cells. The tumor was composed predominantly of infiltrating and superficial collections of cells that formed papillary structures with identifiable fibrovascular cores and psammoma bodies (Figures
Immunohistochemical stains were performed to compare the two neoplasms using automatic tissue staining: Bond Polymer Refine Detection System (Leica Biosystems, Newcastle, UK) with multiple antibodies according to manufacturer’s instruction (Vantana Tucson, Arizona, USA). The colonic adenocarcinoma was positive for CK20, monoclonal CEA, and villin (Figure
Immunohistochemical staining. (a, b) Adenocarcinoma stained with CK20, but not calretinin. (c, d) Malignant mesothelioma showed negative staining with CK20 and positive immunoreactivity with calretinin.
Colorectal cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and women. In contrast, mesothelioma, a neoplasm arising from the mesothelial lining cells of pleura, peritoneum, pericardium, and tunica vaginalis are uncommon and peritoneal MM is an extremely rare tumor [
Patients with peritoneal MM can present with abdominal distention, fatigue, weight loss, and organ impairment such as bowel obstruction as seen in our patient [
The lesson we learned from this case is to keep in mind that MM can coexist with adenocarcinoma and tissue diagnosis is crucial for accurate staging colon cancer before further management. Cytologic examination of ascitic fluid could be an initial assessment to differentiate between peritoneal metastatic adenocarcinoma and mesothelial proliferative lesion. If findings were negative or inconclusive, subsequent CT or ultrasound-guided biopsy or fine needle aspiration of mesentery, peritoneal, and omental irregular area/nodules may as well be used to rule out metastatic carcinoma and assess for mesothelioma. In rare situation of suspicious lesion, laparoscopic exploration with tissue biopsy should lead to definitive diagnosis.
Pathologic diagnosis of peritoneal MM is based on gross findings, microscopic patterns, and immunostaining profile. Grossly, MM usually presents as multiple nodules, plaques, or diffuse thickening of the peritoneum. Solitary mass is uncommon, which is usually benign. MM exhibits variable microscopic types, predominantly epithelioid, sarcomatoid, and mixed biphasic types. The most common type is epithelioid, which shows tubulopapillary, glandular, adenomatoid, microglandular, and solid patterns. Tubulopapillary and glandular patterns as seen in our case consist of a mixture of papillary structures lined with atypical flat, cuboidal, or polygonal cells with fibrovascular cores, glands, and tubules. The tumor papilla needs to be differentiated from primary peritoneal cavity carcinoma extension or metastatic carcinoma with papillary pattern, such as papillary urothelial carcinoma, papillary renal cell carcinoma, and pulmonary adenocarcinoma. In female patients, ovarian papillary serous carcinoma (PSC) is of concern. Differential diagnosis for neoplastic glands and tubules also includes gastrointestinal, pancreatobiliary, and pulmonary adenocarcinomas. Our case had biopsy proven colonic adenocarcinoma. It was easy to assume that the peritoneal findings were due to colonic carcinoma spread through vessels or lymphatic spaces (carcinomatosis). Careful microscopic examination, awareness of different patterns, extensive sampling, and further ancillary studies are critical to identify secondary malignancies arising from an entirely different origin. Exuberant mesothelial hyperplasia, which is more frequently encountered in the peritoneum rather than the pleura, may mimic MM. Our case showed peritoneal tumor with serosa stromal fibroadipose tissue and muscularis propria invasion, which is a diagnostic feature of malignancy in MM. Other features distinguishing MM from hyperplasia include (1) dense cellularity, (2) complex papillae, (3) tubules, (4) disorganized growth, (5) expansion of nodules, (6) cytologic atypia, and (7) necrosis not seen with hyperplasia. Of note, although demonstration of invasion is the key feature of a malignant diagnosis and solitary mesothelial proliferation is usually considered benign, there are exceptions in both entities. In rare situation, the presence of invasion is not required for the diagnosis of MM in solid fragments of mesothelial tumor with histologic features of malignancy [
There is an important subtype of mesothelioma which may be difficult to identify from merely reactive mesothelial proliferation. A well-differentiated papillary mesothelioma of the peritoneum is generally noninvasive, lined with uniform bland mesothelial cells. It does not have multilayering and there is an absence of the common cytologic features associated with malignancies. It is more common in young women. Although it may recur or progress to a more aggressive clearly malignant mesothelioma, this tumor usually has an excellent prognosis and treatment is less aggressive than that applied to MM [
Highly selective panels of immunohistochemical (IHC) stains are needed to distinguish mesothelioma from adenocarcinomas of the gastrointestinal tract. Because both tumors may fail to stain uniformly with commonly known markers, several specific mesothelioma stains and several common adenocarcinoma stains should be used. Often each laboratory will devise their unique staining panels. None of the antibodies used are 100% specific or 100% sensitive. Approximately 10% false positive reactions can occur which may be related to fixation or techniques. Common mesothelial IHC panel includes calretinin, WT-1, CK7, CK5/6, and vimentin. D2-40 also stains with mesothelioma. Colonic adenocarcinoma can stain with CK20, villin, monoclonal CEA, CDX-2, and Moc31. We used mesothelial IHCs CK5/6, calretinin, and adenocarcinoma IHCs monoclonal CEA. It should be noted that monoclonal CEA and WT-1 may stain ovarian PSC. There is infrequent staining CEA in PSC and positive reaction of WT-1 in both mesothelioma and PSC. Our patient was male, so PSC was not in the differential diagnosis. Our case showed typical MM and adenocarcinoma staining patterns with our IHC stains. We also included additional carcinoma IHC stains to rule out that the peritoneal tumors were of different origins: CK7, CK20, and villin for gastrointestinal, urothelial primary tumor, TTF-1 for lung adenocarcinoma, CD10, RCC, and vimentin for clear cell renal cell carcinoma, and P504S and PAX-2 for papillary renal cell carcinoma.
Asbestos is a well-known carcinogen associated with MM [
Complete resection with excision of all visible peritoneal tumors followed by subsequent chemotherapy is a commonly used treatment for limited stage MM [
In conclusion, a review of the existing literature has shown that presenting synchronous colonic adenocarcinoma and coexistent primary peritoneal MM are exceedingly rare but must be considered to prevent incorrect clinical staging. Tissue examination to identify different morphologic patterns and confirm differentiation of tumor origin with immunohistochemistry is critical for definitive diagnosis.
The authors declare that there is no conflict of interests regarding the publication of this paper.