Case Presentation - Summer, 2016
Incidental metastatic colon adenocarcinoma identified by fine needle aspiration of multiple lung nodules
Written by: Nicole Minca, student, Cleveland Clinic School of Cytotechnology, Cleveland, Ohio
Patient Information: 53-year-old male
Patient History: Smoking history of 1 pack per day for 20 years. Patient quit cigarettes in 2010, but still smokes marijuana. No family history or prior history of colorectal cancer. Patient complained of rectal pain and some bleeding with bowel movements. First colonoscopy was unable to be completed due to patient discomfort. Repeat colonoscopy 3 months later found large thrombosed internal hemorrhoids on digital rectal exam and during endoscopy as well as diverticulosis in the sigmoid and descending colon. Three months later, the patient returned with increased anal pain and bleeding as well as weight loss (~50 lbs. in the last year). Chest X-ray performed showed multiple lung nodules. Patient was referred for bronchoscopy to determine primary lung tumor vs. metastatic disease.
Specimen type: EBUS, Bronchial FNA, ThinPrep® non-Gyn-sample
Case provided by: Department of Cytopathology, Cleveland Clinic, Cleveland, Ohio
Cytologic Diagnosis: Positive for malignant cells, Adenocarcinoma favor metastatic colon cancer
Adenocarcinoma of the colon, metastatic to the lung
In the U.S., colorectal carcinoma is the second leading cause of cancer death, subsequent to lung cancer. There are an estimated 93,090 new cases of colon cancer in the U.S. in 2015 and an estimated 49,700 deaths. Risk factors include diet, genetics, inflammatory conditions and environmental factors. If not caught early, adenocarcinoma can invade the blood supply or lymphatics where it has the ability to metastasize to any location in the body. Colorectal adenocarcinoma usually metastasizes to the liver or lungs first. About 34% of the metastatic tumors in the lung are adenocarcinomas. The most common primary sites include breast, kidney and colon. Each of these primary carcinomas can have characteristic cytologic features that can help determine their origin. Cells from adenocarcinoma of the colon can be distinguished by a tall, columnar appearance (cigar shape) with hyperchromatic nuclei as well as a necrotic background. The ability to determine whether a malignancy is from a primary lung carcinoma or a metastasis is important in the prognosis and treatment of the patient. Often, the diagnosis depends upon immunohistochemical (IHC) stains being performed.
Metastatic colorectal adenocarcinoma can be confused with primary lung mucinous adenocarcinoma because it shares similar cytologic features, which can only be distinguished using IHC stains. Mucinous adenocarcinomas of the lung express CK7 and can sometimes express CK20, which is also expressed in colorectal adenocarcinomas. This can be a pitfall in diagnosing these cases. It is important to run a full IHC panel to include Cdx2 because it is a sensitive and specific marker for differentiating metastatic colorectal adenocarcinoma from primary lung adenocarcinoma. This case is interesting because the patient presented with a carcinoma of unknown primary origin (CUP). The patient’s lack of previous colorectal cancer diagnosis and negative colonoscopies as well as smoking history, made it imperative to use immunohistochemical stains to determine the correct diagnosis. After running a comprehensive IHC panel (CK7-, CK20+, Cdx2+, TTF-1- and Napsin A-), it was determined that the metastasis came from a colon primary and clinical correlation was recommended. The patient returned for a biopsy of the anorectal mass which was diagnosed as invasive adenocarcinoma.
Colorectal Adenocarcinoma can have common clinical presentations that include iron-deficiency anemia, change in bowel habits, blood in stool, abdominal pain and intestinal obstruction or perforation. These symptoms may not be present in earlier stages of the disease. Regional lymph nodes, lung, liver and peritoneum are the most common sites for colon cancer to metastasize. Metastatic cancer to the lung can present with chest pain, cough, bloody sputum, shortness of breath, weakness and weight loss, but in most cases, there are no lung-related symptoms. A chest X-ray, CT scan, or PET scan can show discrete single or multiple pulmonary nodules, interstitial infiltrates, or endobronchial lesions raising concern for metastatic disease. Cannonball appearing nodules are associated with metastatic colorectal cancer and sarcoma, while a miliary pattern is associated with metastatic thyroid and ovarian cancer.
Treatment and Prognosis:
Treatment can include chemotherapy, radiation, and surgery. Metastatic adenocarcinoma of the colon to the lung can have a multidisciplinary approach. It begins with a systemic treatment of chemotherapy, but can be accompanied by radiation, surgery, or both. In order to be a candidate for surgery, the patient must undergo a pulmonary function or cardiopulmonary exercise test to determine if the procedure has a greater chance of success. If the surgeon believes that metastasectomy (wedge resection of the malignant nodule) is favorable, that is another treatment option.
The presence of metastasis from the colon to the lung decreases the overall prognosis due to the advanced stage of the primary disease. Surgical resection can be performed to remove solitary pulmonary nodules via lobectomy with a 5-year survival rate of 40% for metastatic colon cancer.
Cytologically adenocarcinoma of the colon presents with highly cellular smears containing groups of disorderly crowded sheets as well as numerous single, atypical cells which are characteristic of invasive adenocarcinoma. Palisading nuclei and/or acinar formations may be present. The nuclei present with the typical malignant criteria: enlarged, pleomorphic nuclei with irregular nuclear membranes, irregular coarse dark chromatin and prominent nucleoli. The cytoplasm shows glandular differentiation with a granular basophilic appearance and varying degrees of mucin vacuolization. Depending on the differentiation of the tumor, cells can present as tall columnar cells with elongated, cigar shaped nuclei or rounded cells with irregular nuclei. Dirty tumor diathesis is present in the background and it is common for metastatic colon cancer to carry necrosis and neutrophils with it to the secondary area.
Since this patient had no known primary disease and is a smoker, the differential based on chest X-ray included lung infection, lung cancer, or metastatic disease. Solitary nodules are nonspecific and can be indicative of any type of cancer or benign etiology. Multiple lung nodules are often caused by metastatic disease, but can also be caused by benign conditions such as sarcoidosis, bacterial or fungal infections and hamartomas. Based on the cytology, the differential diagnoses include primary bronchioloalveolar carcinoma, squamous cell carcinoma and spindle cell neoplasm.
Bronchioloalveolar carcinoma (BAC) is a primary adenocarcinoma of the lung that is non-invasive and can rarely be diagnosed cytologically. On chest X-ray, BAC can be single or multiple nodules, or diffuse. Cytologically they are tall, columnar cells with eccentrically placed nuclei and abundant mucin in the cytoplasm. BAC is positive for CK7 and CK20 and negative for TTF-1 and Cdx2.
Squamous cell carcinoma is a common tumor of the lung. It can form cavitary nodules seen on CT scans that are filled with necrosis. Squamous cell carcinoma has a spindle cell form that can resemble the elongated hyperchromatic nuclei of colon cancer. It usually presents in sheets with bizarre shaped single cells. It stains positive for p63, p40 and CK5/6.
Sarcomatoid carcinoma of the lung is a rare poorly differentiated non-small cell carcinoma with sarcoma like spindle cell differentiation. Cytologically they include cells that have elongated nuclei with hyperchromasia and wispy cytoplasm as single cells or in groups. They can stain positive for AE1/3, CK7 and p53, while staining negative for CK20 and TTF-1.
Because there was no known primary, immunohistochemical staining was vital to establishing the precise diagnosis. Adenocarcinoma of the colon is TTF-1 and CK7 negative and CK20 positive. However, both adenocarcinoma of the colon and bronchioloalveolar carcinoma have been reported to be CK7 & CK20 positive, creating a challenge for the pathologist. The critical stain in this case was the Cdx2 which stains positive for adenocarcinoma of the colon 70-98% of the time.
- Cibas E, Ducatman B. Cytology Diagnostic Principles and Clinical Correlates. 4th edition. Philadelphia, PA: Elsevier; 2014.
- DeMay R. The Gastrointestinal Tract. In: The Art and Science of Cytopathology, Exfoliative Cytology Volume 1. 2nd ed. 2012. Chicago, IL: ASCP Press; 2012.
- Saad R, et al. Usefulness of Cdx2 in Separating Mucinous Bronchioloalveolar Adencarcinoma of the Lung From Metastatic Mucinous Colorectal Adenocarcinoma. Am J Clin Pathol. 2004;122(3):421-7. doi:10.1309/UMF715KRG2V198YD.
- Schwartz DS. Secondary Lung Tumors. http://emedicine.medscape.com/article/426820-overview. Updated December 8, 2014. Accessed February 29, 2016.
- Shah R, et al. Expression of Cytokeratin 20 in Mucinous Bronchioloalveolar Carcinoma. Hum Pathol. 2002;33(9):915-920. doi:10.1053/hupa.2002.126876.
- Siegel R, et al. Cancer Statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29. doi:10.3322/caac.21254.
- Qiu M, et al. Pattern of Distant Metastases in Colorectal Cancer: a SEER based study. Oncotarget. 2015;6(36):38658-38665. doi:10.18632/oncotarget.6130.
- Villeneuve PJ, et al. Surgical Management of Colorectal Lung Metastasis. Clin Colon Rectal Surg. 2009;22(4):233-241. doi:10.1055/s-0029-1242463.
- Yousem S, et al. Bronchioloalveolar Carcinoma: A review of Current Concepts and Evolving Issues. Arch Pathol Lab Med. 2007;131(7):1027-1032. doi:10.1043/1543-2165(2007)131[1027:BCAROC]2.0.CO;2.