55 Metastasis to the Appendix from Lung Adenocarcinoma Manifesting as Acute Appendicitis: A Case Report Yi-Fong Su*, Chi-Lu Chiang*, Fang-Chi Lin*, Chun-Ming Tsai*,** Appendix metastasis from lung adenocarcinoma is very rare. Metastasis-induced acute appendicitis is extremely rare. We present the case of a 77-year-old woman with stage IV lung adenocarcinoma who presented with acute appendicitis. She was admitted to the emergency department with complaints of right lower quadrant pain, nausea and vomiting for 12 hours. Contrast-enhanced abdominal computed tomography showed a dilated appendix with a thickened wall suggestive of acute appendicitis. She underwent appendectomy, and the pathological examination of the appendiceal specimen demonstrated metastatic poorly differentiated adenocarcinoma from the lung. After treatment for acute appendicitis, she was discharged and recovered uneventfully, and was then referred to our thoracic oncology department to resume treatment for her lung cancer. (Thorac Med 2015; 30: 55-60) Key words: lung cancer, adenocarcinoma, acute appendicitis Introduction dence of adenocarcinoma has increased in both males and females [2-3]. In Taiwan, adenocar- Lung cancer is the most common malignan- cinoma is the most common histological type cy worldwide in terms of incidence and mor- of NSCLC [2,4]. Appendix metastasis from tality in both men and women, and is also the lung cancer is very rare, and may occur in the leading cause of cancer death in Taiwan. Lung late stages of the disease. We present a 77-year- cancer metastasis is common, and the most old woman with stage IV lung adenocarcinoma commonly involved sites are the brain, bones, who presented with acute appendicitis. She liver, adrenal glands and other regions of the underwent appendectomy, and pathology of the body [1]. Non-small cell lung cancer (NSCLC) appendiceal specimen demonstrated metastatic accounts for approximately 85% of lung cancer poorly differentiated adenocarcinoma from the cases, presents as metastatic disease in over lung. half of all cases, and is associated with a poor prognosis [1-2]. In the past 2 decades, the inci- *Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; **Division of Thoracic Oncology, Taipei Veterans General Hospital, Taipei, Taiwan Address reprint requests to: Dr. Chun-Ming Tsai, Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan 胸腔醫學：民國 104 年 30 卷 1 期 56 Yi-Fong Su, Chi-Lu Chiang, et al. Fig. 1. Computed tomography scan showing a thickened wall and distended appendiceal tip, with infiltration of soft-tissue in the ileocecal region suggestive of acute appendicitis. Case Report A 77-year-old female patient was admitted to the emergency department with complaints of right lower quadrant pain, nausea and vomiting for 12 hours. A physical examination revealed notable tenderness to palpation in all quadrants, with rebound and guarding. Her vital signs were within normal limits, and laboratory results re- vealed a white blood cell count of 13400/mm3 with 93% neutrophils, and a C-reactive protein level of 17.25 mg/dL. Her medical history indi- Fig. 2. Adenocarcinoma involving the serosa of the appendix (H&E, 40×). cated that she had been diagnosed with stage IV adenocarcinoma of the lung with brain metas- tasis (EGFR mutation: wild type) and was sub- sequently followed at our thoracic oncology de- partment for 1 year. She had been given chemo- therapy treatment with 4 cycles of pemetrexed plus carboplatin and had a partial response of the lung lesion. Gamma knife radiosurgery was used to treat her brain metastasis and achieved a partial response. Contrast-enhanced abdomi- nal computed tomography (CT) was performed in the emergency room, and showed a dilated Fig. 3. Adenocarcinoma involving the serosa of the appendix (H&E, appendix with a thickened wall suggestive of 200×). Thorac Med 2015. Vol. 30 No. 1 Metastasis to the Appendix from Lung Adenocarcinoma 57 Fig. 4. Strong TTF-1 immunopositivity of the tumor and lympho- Fig. 6. Negative CK-20 immunopositivity of the tumor and vascular invasion (TTF-1 immunostain, 200×). lymphovascular invasion (CK-20 immunostain, 200×). revealed that the tumor cells strongly expressed thyroid transcription factor-1 (TTF-1) (Figure 4) and cytokeratin-7 (CK-7) (Figure 5), but showed negative reactivity for CK-20 (Figure 6). These findings confirmed adenocarcinoma of the lung. The patient was discharged with an uneventful recovery. Discussion Metastasis-induced acute appendicitis is an Fig. 5. Strong CK-7 immunopositivity of the tumor and lympho- uncommon complication [5]. Previous studies vascular invasion (CK-7 immunostain, 200×). have reported metastasis to the appendix from carcinomas of the breast, lung, pancreas, stom- ach, ovary, liver and kidney [5-11]. It has also acute appendicitis (Figure 1). There was no been reported that metastatic cancers of the ap- evidence of intraperitoneal metastasis in the pendix do not present with any specific symp- CT scan. Surgical exploration revealed a firm toms or signs [8-9]. Obstruction of the appendi- swelling appendix with perforation, and ap- ceal lumen due to metastasis as seen in our case pendectomy was performed. There was no peri- has been described in the majority of reported toneal metastasis or evidence of metastasis on cases, and this may play a key role in the mech- the appendix. A histopathological examination anism of acute appendicitis [8-10]. Malignan- showed multiple foci of adenocarcinoma metas- cies are a rare but known cause of appendiceal tasis in the appendix mucosa and serosa (Figures obstruction and inflammation, most commonly 2, 3). Immunohistochemical (IHC) staining involving primary tumors such as carcinoids or 胸腔醫學：民國 104 年 30 卷 1 期 58 Yi-Fong Su, Chi-Lu Chiang, et al. adenocarcinomas. Cases of appendicitis from adenocarcinomas and carcinoid tumors. Pri- metastatic lung adenocarcinoma are exceed- mary lung cancers themselves most commonly ingly rare [12-13]. The rate of perforation has metastasize to the brain, bones, liver, and ad- been reported to be 70% in cases of metastasis- renal glands. IHC staining of a biopsy is often induced acute appendicitis, compared to only helpful in determining the original source. TTF- 40% for simple acute appendicitis [7]. This high 1, CK-7 and CK-20 have recently been reported rate of perforation may be explained by the to be useful in distinguishing between primary local effect of metastasis on the ability of the and metastatic lung adenocarcinoma. Previous appendix to limit inflammation, obstruction of studies have confirmed that the expressions of the lumen, or the general immunocompromised CK-7, CK-20, and TTF-1 are useful markers for condition of cancer patients. Appendix cancer the diagnosis of lung cancers and for the differ- is extremely rare, affecting only an estimated ential diagnosis of primary pulmonary adeno- 600 to 1,000 Americans each year. It accounts carcinomas from metastatic adenocarcinomas. for only 0.4% of gastrointestinal tumors and is TTF-1 is a sensitive IHC marker for pulmonary usually diagnosed incidentally in approximately and thyroid adenocarcinomas and is expressed 1% of all appendectomies [10-11]. The most consistently in the terminal respiratory unit, common benign tumors of the appendix are which is composed of peripheral airway cells. carcinoids, and adenocarcinomas are the most Furthermore, the expression of TTF-1 has been common appendiceal malignancies. However, reported to be maintained in 72% of adenocar- primary adenocarcinoma originating in the ap- cinomas of the lung [15]. pendix is rare, and usually resembles metastatic Cytokeratins are intermediate filament adenocarcinoma. Carcinoids account for 2/3 of proteins present in epithelial cells. They are the cases of appendix cancer, with cystadeno- expressed in normal organs and in the tumors carcinomas accounting for 20% and adenocar- that arise from them. IHC staining is used to cinomas, 10% [10-11]. evaluate the pattern of cytokeratin expression in Carcinoids and adenocarcinomas with typi- cells of epithelial origin. Positive CK-7 stain- cal pathological features and specific tumor ing is seen in lung, breast, endometrium, ovary, markers can be easily detected in the appendix. cervix, salivary gland, and thyroid cancers, In patients who present with metastatic can- cholangiocarcinoma, and adenocarcinoma of cer, determining the primary site of origin may the pancreas. In contrast, CK-20 expression is have a major impact on the choice of treatment observed in all colorectal adenocarcinomas and and outcome. However, in spite of clinical, in the majority of gastric and pancreatic tumors. radiographic, and routine histologic studies, Prostate, kidney, and adrenocortical carcinomas, the primary site of origin remains uncertain in sarcomas, carcinoids, hepatocellular carcino- nearly 15% of cases [14]. A large proportion of mas and thymomas are negative for both CK-7 these cases are adenocarcinomas, and they are and CK-20 staining, while a large proportion of challenging to treat. In our case, strong immu- pancreatic, biliary, bladder and gastric tumors noreactivity for CK-7 and TTF-1 suggested the express both CK-7 and CK-20 [16]. diagnosis of metastatic lung adenocarcinoma. In previous reports, the interval between Negativity for CK-20 excluded other possible the presentation of cancer and the presenta- Thorac Med 2015. Vol. 30 No. 1 Metastasis to the Appendix from Lung Adenocarcinoma 59 tion of appendicitis ranged from 1 month to 5 5. Yoon WJ, Yoon YB, Kim YJ, et al. Secondary appendiceal years [10-11], compared to nearly 1 year for tumors: a review of 139 cases. Gut Liver 2010; 4(3): 351- our patient. With the improved survival of lung 6. 6. Ratanarapee S, Nualyong C. Acute appendicitis as pri- cancer patients, metastasis to the appendix may mary symptom of prostatic adenocarcinoma: report of become more common in the future. While a case. J Med Assoc Thailand = Chotmaihet thangphaet metastasis is an uncommon cause of appendi- 2010; 93(11): 1327-31.