There are four types of appendix tumors: Epithelial tumors, mesenchymal tumors, lymphomas, and secondary tumors. Epithelial tumors are grouped categorized as premalignant lesions, carcinoma, neuroendocrine tumors. The most common epithelial tumors are neuroendocrine neoplasias. Appendix tumors that are completely or partially composed of neuroendocrine cells are divided into two different categories: Classic carcinoid tumors and GCCT, and their variants. Tumors showing both glandular and endocrine differentiation are called “amphicrine tumors”. The amphicrine tumor of the appendix is goblet cell carcinoid. In the WHO classification, this type of tumors that advance aggressively are called “mixed carcinoid adenocarcinoma” in the “mixed adenoneuroendocrine carcinoma” group, and “adenocarcinoma”, which develops on the goblet cell carcinoid. The goblet cell carcinoid is called adenocarcinoid of goblet cell type, mucinous carcinoid tumor, and microglandular carcinoma, as well as crypt cell carcinoma. Microscopically, it is characterized predominantly by submucosal growth. Extending into the muscle and serosa is common. However, the mucosa is typically preserved except tumor islets and obvious connections between crypt bases. The tumor itself is composed of small uniform goblet cell islets, which are generally arranged in the microglandular style and sometimes accompanied by extracellular mucus. The typical lesion consist of small uniform nests of goblet cells, often arranged in a microglandular fashion and sometimes accompanied by extracellular mucus.
Goblet cell carcinoids rare
GCCs usually occur in older patients, generally median age was 58 years (range 31-73) and no definite sex predominance. Clinical presentation followed two distinct patterns: Acute appendicitis or chronic symptoms associated with a pelvic mass. The pathogenesis is unclear however the tumor likely arises from pluripotent intestinal epithelial crypt base stem cells. Loss of Notch signaling may be the driver mutation with other successive downstream mutations likely favors them into progressing and behavior similar to poorly differentiated adenocarcinoma with minimal neuroendocrine differentiation[9,15,16].
Goblet cell carcinoid is a more aggressive tumor than classic carcinoid, if the tumor shows transmural involvement or if it has extended to the cecum at the time of the operation[3,11,13]. In 2008, Tang et al, GCC patients are divided into three groups (A, B, C). Typical GCC (Group A); adenocarcinoma ex GCC, signet ring cell type (Group B); adenocarcinoma ex GCC, poorly differentiated carcinoma type (Group C). Typical GCC (Group A) was defined as well-defined goblet cells arranged in cluster or in a cohesive linear pattern, with minimal cytologic atypia and architectural distortion of the appendical wall, and minimal to no desmoplasia. Adenocarcinoma ex GCC, signet ring cell type (Group B) was defined as goblet cells or signet ring cells arranged in irregular large clusters, with the lack of confluent sheets of cells in a discohesive single file or single cell infiltrating pattern with significant cytologic atypia, and desmoplasia and associated destruction of the appendiceal wall[15,16]. Adenocarcinoma ex GCC, poorly differentiated carcinoma type (Group C) was defined with the least focal evidence of goblet cell morphology and a component (> 1 low power field or 1 mm2) that is not otherwise distinguishable from a poorly differentiated adenocarcinoma[15,16].
The tumor itself, as in our case study, is composed of small uniform goblet cell islets, which are generally arranged in the microglandular style and sometimes accompanied by extracellular mucus. The histochemical stainings, mucicarmine, and CEA stainings are always positive. There is generally CK20 in all cases and the focal style CK7 positivity in approximately 70% of the cases. In our case, in agreement with the literature, tumor cells were positive for CEA, CK7, CK20, and neuroendocrine markers.
Fifty percent of patients with these tumors, who are rarely seen, often go to hospitals in the 50s or 60s with abdominal pain and palpable masses. Others cases, like ours, were detected incidentally in the appendectomy specimens removed from the patients, who arrived at the hospital with acute abdominal pain and symptoms of acute appendicitis and were taken to surgery diagnosed with acute appendicitis[3,4,12,14-18]. In addition to the characteristic histological appearance, as seen in our cases, they showed widespread invasion of the mesoappendix and perineural.
Adenocarcinoma developing on the goblet cell carcinoid ground constitutesa significant portion of mixed adenoneuroendocrine carcinoma. The adenocarcinoma component is in the form of signet ring cell carcinoma or poorly differentiated carcinoma. In these tumors, the goblet cell carcinoid tumor area should cover at least low-power fields (or 1 mm2) of the tumor. The signet ring cell type is composed of cells aligned in a single row or that form irregular groups with the appearance of a signet ring as well as goblet cell carcinoid areas. Our case was diagnosed as “mixed adenoneuroendocrine carcinoma diagnosis” because of the presence of the signet ring cell component developing from the goblet cell carcinoid.
In our case, the Ki-67 labeling index was 3%-10%. In the ENETS-2007 pathologic TNM staging, < 1 cm tumors are T1, ≤ 2 cm tumors with subserosa or mesoappendix invasion of less than 3 mm are T2, > 2 cm tumors with subserosa or mesoappendix invasion of > 3 mm are T3, and tumors with the peritoneum or other organ invasion are T4. GCCT are more aggressive than classical carcinoid tumors. Metastases have been documented in 8%-20% of the cases[11,13,15,16]. There are liver, ovarian, and peritoneal metastases during the diagnosis in approximately 10% of patients. While five-year survival is between 50%-80% for the disease when limited to the appendix, it is less than 20% in the presence of distant metastases. In the literature, it is reported that an appendectomy should be sufficient for the treatment of tumors smaller than 1 cm that do not have no serious mesoappendix involvement and a low Ki-67 index[4,20-22].
The recommended treatment for goblet cell carcinoid, whether pure or combined, is a right hemicolectomy, especially if the tumor has spread beyond the appendix and/or shows a high mitoticcount. Although many authors suggest routine right hemicolectomy for goblet cell carcinoids, this recommendation has been questioned, and some authors believe that appendectomy alone may be sufficient if the appendical margin is clear, there is no evidence of spread into the periappendiceal soft tissue, the mitotic count is no more than two mitoses per 10 HPF, and there are no features of mixed goblet cell carcinoid-adenocarcinoma[3,15,16]. Both European and North American Neuroendocrine tumor societies guidelines recommend right hemicolectomy after appendectomy due to the high rate of metastases and its impact on prognosis. Our cases underwent a right hemicolectomy after the diagnosis of GCC and mixed adenoneuroendocrine carcinoma and have been made. As a result, because it is known that GCCT are more aggressive than classical carcinoid tumors but they do not show malignant behavior like adenocarcinomas, their histological identification is important.
Finally, GCCs are unique to the appendix. Appendiceal NETs asymptomatic. Carcinoid synrome is very uncommon. The symptoms resemble acute appendicitis. Since the diagnosis is usually established post appendectomy, appendectomy materials should be examined carefully. NET and adenocarcinomas developing on the goblet cell carcinoid should definitely be kept in mind in terms of malignancy. Grading and staging play an important role in treatment and prognosis.