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  Table of Contents    
CASE REPORT  
Year : 2014  |  Volume : 57  |  Issue : 1  |  Page : 120-123
Incidentally discovered goblet cell carcinoid clinically presenting as acute intestinal obstruction: A case report with review of literature


1 Department of Pathology, J N Medical College, AMU, Aligarh, Uttar Pradesh, India
2 Department of General Surgery, J N Medical College, AMU, Aligarh, Uttar Pradesh, India

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Date of Web Publication17-Apr-2014
 

   Abstract 

Goblet cell carcinoid (GCC) is a rare variant of carcinoid tumor that exclusively involves the appendix. It usually occurs in 5 th -6 th decade with the most common clinical presentation being acute appendicitis. The natural history of this tumor is intermediate between carcinoids and adenocarcinomas. We here report a case of GCC diagnosed incidentally in a patient presenting with acute intestinal obstruction. Ultrasonographic examination supported the clinical diagnosis of acute intestinal obstruction, following which the patient underwent laparotomy and resection of ileum along with appendix was done. On gross pathological examination, a nodular growth was present on the tip and body of appendix that was yellow in color with a semi-solid to mucoid consistency on cut section. On microscopy, lakes of mucin with few acinar structures floating in them were seen. The submucosa as well as serosa were infiltrated by clusters of goblet cells and well-formed acini, with little atypia. Glands and nests were positive for per-iodic acid Schiff and immunohistochemistry showed focal chromogranin positivity in glandular structures, thereby confirming the diagnosis of GCC. Although the prognosis of GCC is better than adenocarcinomas, it is one of the carcinoids having a poorer outcome when compared with other variants of carcinoid tumor. Therefore, it is important to rule out other differential diagnoses of goblet cell carcinoid, the most important being mucinous adenocarcinomas.

Keywords: Adenocarcinoma, appendix, goblet cell carcinoid

How to cite this article:
Afroz N, Shamim N, Sofi LA, Rizvi SA. Incidentally discovered goblet cell carcinoid clinically presenting as acute intestinal obstruction: A case report with review of literature. Indian J Pathol Microbiol 2014;57:120-3

How to cite this URL:
Afroz N, Shamim N, Sofi LA, Rizvi SA. Incidentally discovered goblet cell carcinoid clinically presenting as acute intestinal obstruction: A case report with review of literature. Indian J Pathol Microbiol [serial online] 2014 [cited 2018 Nov 21];57:120-3. Available from: http://www.ijpmonline.org/text.asp?2014/57/1/120/130918



   Introduction Top


Cancer of the appendix is an uncommon disease. [1] Appendiceal carcinoids however are found in 1 out of every 300 appendectomies. The goblet cell carcinoid (GCC), an uncommon neuroendocrine tumor of the vermiform appendix, is a separate entity from adenocarcinoma and carcinoid tumors and was first recognized in 1974. [1] In general, GCC comprises approximately 6% of appendiceal carcinoids and usually occurs in the pure form. [2] The number of patients who were diagnosed with this neoplasm based on the Medline search is less than 600 worldwide.The exact biological behavior of this tumor is uncertain. We report a case of GCC of appendix owing to its rarity, along with its distinctive histopathological, immunohistochemical and prognostic features and its differentiation from conventional mucinous adenocarcinoma.


   Case Report Top


This was a case report of a 50-year-old male patient who presented with a 5 day history of pain in abdomen along with nausea and vomiting. The pain was initially localized to the lower abdomen and later involved the whole abdomen. The vomiting occurred off and on, was non-projectile and non-bilious. On examination, he was apyrexic with rebound tenderness in the right iliac fossa. No edema, organomegaly or lymphadenopathy was noted. The patient was a known case of hypertension along with a history of umbilical hernia since 2 years.

Blood investigations revealed a white cell count of 14.6 × 10 9 /L with neutrophilia and a raised erythrocyte sedimentation rate. Ultrasonographic examination of abdomen revealed dilated bowel loops with sluggish peristalsis and no free fluid, thereby favoring the clinical diagnosis of intestinal obstruction.

A provisional diagnosis of acute intestinal obstruction was made and patient was taken up for laparotomy. A portion of terminal ileum (approximately 10 cm) along with cecum and appendix were resected. No enlarged lymph node was found.

On gross examination, small intestinal segment measured 10.5 cm × 2.7 cm with normal appearing mucosa and no evidence of any growth, ulcer or stricture. The appendix was received separately and measured 5 cm in length with a globular growth at the tip measuring 2.5 cm × 1.5 cm. Cut section of the growth was solid with cystic areas containing mucoid material [Figure 1].
Figure 1: Gross picture of the specimen showing globular growth at the tip with solid and cystic areas containing mucoid material

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On microscopic examination of sections from the tip, body and proximal end of appendix, a mucin producing growth comprising of glands and isolated nests of cells having mucinous/goblet cell like appearance involving the submucosa, muscle layer as well as serosa was present. The overlying mucosa however, appeared normal except for foci of ulceration. High grade features such as single file pattern, fusion of glands or sheets of signet cells were absent. Pools of mucin were present around the glands [Figure 2]a and b] and were scattered throughout the wall. Mitotic activity was minimal as only 0-2 mitotic figures per 10 high power fields were seen. Glands and nests were positive for per-iodic acid Schiff (PAS) while immunohistochemistry revealed focal positivity for chromogranin [Figure 3]a and b], thereby confirming the diagnosis of goblet cell adenocarcinoid. Furthermore, CK20 immunostaining showed strong positivity in tumor cells that were arranged in nests as well as in those lying scattered as individual cells, although the latter were infrequent in our case. The sections from caecum and ileum showed changes of acute degeneration, inflammation and edema and were free from tumor infiltration. The above mentioned features favored a Group A grade of GCC.
Figure 2: (a) Low power photomicrograph showing the tumor composed of goblet cells arranged in clusters (nests) in submucosa with a bland infiltrative pattern (H and E stain, 10). (b) High power photomicrograph depicting individual cells having eosinophilic, vacuolated and focally granular cytoplasm (H and E stain, 40)

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Figure 3: (a) High power photomicrograph showing cells with cytoplasmic periodic acid-Schiff (PAP) positivity (PAS stain, 40). (b) Low power photomicrograph showing focal chromogranin positivity done using PAP technique of IHC 10

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Urinary level of 5-Hydroxyindoleacetic acid done post-operatively was found to be within normal limits. Patient recovery was uneventful and 3 months after follow-up, patient is doing well.


   Discussion Top


GCC accounts for less than 5% of primary tumors of the appendix. [3] It shows equal sex predilection with higher incidence among white race. [1] The mean age for GCC is 58.8 years, between malignant carcinoid (38 years) and mucinous adenocarcinoma (60 years). [1] The age of our patient was 60 years.

GCC is included under the general heading of mixed (composite) glandular-endocrine-cell carcinomas. [4] The diagnosis is almost always made post-operatively [5] and is essentially made on histological grounds after surgery. The tumor cells proliferate sparsely and do not form nodules leading to diffuse thickening, fibrous proliferation and contraction of the appendiceal lumen, causing appendicitis. Hence, the surgical resection margins should be examined microscopically in all appendectomy specimens, especially in older patients, in whom these tumors most often occur. [6]

In our case, the globular swelling seen at the tip of the appendix indicated accumulation of extracellular mucin. Other manifestations include asymptomatic patients, intussusception, a palpable mass, gastrointestinal bleeding, chronic intermittent lower abdominal pain and secondary genitourinary complications. Our reported case did not lead to any complication; neither did it have any features of carcinoid syndrome.

When microscopically evaluated, atypical cells show a prominent submucosal growth pattern with diffuse infiltration from the submucosal layer to the subserosal layer without destroying the appendiceal structure particularly sparing the mucosa. The hallmark of GCC is the presence of individual glands separated by smooth muscle and the lining cells contain intracytoplasmic mucin. [6] In our case this was evident in PAS stained tissue.

GCC should be sharply distinguished from ordinary carcinoid tumors of the appendix, since the former could behave biologically like carcinoma. The mode of growth with concentration of the tumor elements within the basal part of the mucosal lamina propria, the pattern of invasion, growing diffusely through the layers of the wall without causing necrosis or much tissue destruction are more compatible with a carcinoid than with an adenocarcinoma. GCCs can be easily diagnosed when they are of pure type. The distinction between GCC and conventional carcinoid is based on a quantitative estimation of mucin production, since many carcinoids contain a little mucin. [7]

Pathologically, GCC are classified into three groups: [8] Typical GCC (Group A) with well-defined goblet cells arranged in clusters or cohesive linear pattern, minimal cytologic atypia, minimal to no desmoplasia, minimal architectural distortion of the appendiceal wall and degenerative change with extracellular mucin as was seen in our case. In adenocarcinoma ex GCC, signet ring cell type (Group B) goblet cells or signet ring cells are arranged in irregular large clusters, but lack confluent sheets of cells, along with discohesive single file or single cell infiltrating pattern, significant cytologic atypia, desmoplasia and associated destruction of the appendiceal wall. Adenocarcinoma ex GCC, poorly differentiated carcinoma type (Group C) shows at least focal evidence of goblet cell morphology and a component (> 1 low power field or 1 mm 2 ) not otherwise distinguishable from a poorly differentiated adenocarcinoma, which may appear as either (a) gland forming, (b) confluent sheets of signet ring cells, or (c) undifferentiated carcinoma.

Histogenetically, current evidence suggests that GCC is a distinct tumor with a histogenesis different from that of typical carcinoid (i.e., endocrine cells in the mucosal stroma). The nests of goblet cells are larger than normal, arising from a pluripotent cell (stem cell) as intestinal amine precursor uptake and decarboxylase cell with endodermal origin with divergent neuroendocrine and mucinous differentiation. [5] Due to copious production of acid mucin, the cells are strongly positive for mucicarmine, PAS diastase and alcian blue. Because GCC is crypt cells derived, immunohistochemically they show positivity for cytokeratin 20 (CK20), CK7 (with the positivity of CK20 more than CK7), neuron-specific enolase (NSE), chromogranin A, serotonin, lysozyme, PGP 9.5, IgA and vimentin. [9] Neuroendocrine granules in the cytoplasm of the cells are reactive for NSE, chromogranin A, Synaptophysin, Grimelius stain, Fontana-Masson stain, serotonin, substance P and S-100 protein. On the basis of molecular genetics, unlike adenocarcinomas, K-ras and beta-catenin expression is absent in GCC. These tumors also show allelic loss of chromosomes 11q, 16q and 18q, similar to ileal carcinoids. [10]

Even though GCC has a more aggressive phenotype than benign carcinoid tumors, the prognosis is generally good in a patient who is treated by simple appendectomy. In some patients however a more radical procedure is indicated especially in the presence of diffuse appendiceal involvement. [5] GCCs metastasize in 15-30% of cases, particularly in higher age group, compared with 2-5% in appendiceal carcinoids to the ovaries, pelvis, abdominal cavity, rib, vertebra and lymph nodes through lymphatic vessels, transcoelomic and intraperitoneal invasion. [9] The prognosis of these tumors is estimated to be somewhere between carcinoids and well-differentiated adenocarcinoma of the appendix. In a recent study by Pham et al., the disease-specific 5-year survivals for Stages I, II, III and IV were 100%, 76%, 22% and 14%, respectively. It was also noted that adjuvant chemotherapy with 5-fluorouracil and leucovorin regimen is minimally effective against Stage III and IV GCC. [11]


   Conclusion Top


In "suspected appendicitis" or "suspected intestinal obstruction" presenting with or without mass requiring surgery, GCC should be considered as a differential diagnosis. Moreover it is important to rule out other differential diagnoses of GCC, the most important being mucinous adenocarcinomas. Due to the prognostic importance of this entity, we recommend that appendices harboring a GCC be processed in their entirety in order to rule out foci of any higher grade lesion.

 
   References Top

1.McCusker ME, Coté TR, Clegg LX, Sobin LH. Primary malignant neoplasms of the appendix: A population-based study from the surveillance, epidemiology and end-results program, 1973-1998. Cancer 2002;94:3307-12.  Back to cited text no. 1
    
2.Stancu M, Wu TT, Wallace C, Houlihan PS, Hamilton SR, Rashid A. Genetic alterations in goblet cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors. Mod Pathol 2003;16:1189-98.  Back to cited text no. 2
    
3.Gallegos NC, Milroy C, Linehan IP, Boulos PB. Crypt cell carcinoma of the appendix. Eur J Surg Oncol 1992;18:386-7.  Back to cited text no. 3
    
4.Wojcik EM, Selvaggi SM. Goblet-cell carcinoid tumor in peritoneal fluid: A case report. Diagn Cytopathol 1991;7:155-7.  Back to cited text no. 4
    
5.Butler JA, Houshiar A, Lin F, Wilson SE. Goblet cell carcinoid of the appendix. Am J Surg 1994;168:685-7.  Back to cited text no. 5
    
6.Burke AP, Sobin LH, Federspiel BH, Shekitka KM, Helwig EB. Goblet cell carcinoids and related tumors of the vermiform appendix. Am J Clin Pathol 1990;94:27-35.  Back to cited text no. 6
    
7.Bak M, Asschenfeldt P. Adenocarcinoid of the vermiform appendix. A clinicopathologic study of 20 cases. Dis Colon Rectum 1988;31:605-12.  Back to cited text no. 7
    
8.Tang LH, Shia J, Soslow RA, Dhall D, Wong WD, O'Reilly E, et al. Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. Am J Surg Pathol 2008;32:1429-43.  Back to cited text no. 8
    
9.Anderson NH, Somerville JE, Johnston CF, Hayes DM, Buchanan KD, Sloan JM. Appendiceal goblet cell carcinoids: A clinicopathological and immunohistochemical study. Histopathology 1991;18:61-5.  Back to cited text no. 9
    
10.Roy P, Chetty R. Goblet cell carcinoid tumors of the appendix: An overview. World J Gastrointest Oncol 2010;2:251-8.  Back to cited text no. 10
    
11.Pham TH, Wolff B, Abraham SC, Drelichman E. Surgical and chemotherapy treatment outcomes of goblet cell carcinoid: A tertiary cancer center experience. Ann Surg Oncol 2006;13:370-6.  Back to cited text no. 11
    

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Correspondence Address:
Nishat Afroz
Department of Pathology, J N Medical College, AMU, Aligarh - 202 002, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.130918

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