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Goblet cell carcinoid of appendix: A rare case with literature review
CASE REPORT – OPEN ACCESS International Journal of Surgery Case Reports 4 (2013) 334–337
Contents lists available at SciVerse ScienceDirect
International Journal of Surgery Case Reports journal homepage: www.elsevier.com/locate/ijscr
Goblet cell carcinoid of appendix: A rare case with literature review Bhaskar Mitra a,∗ , Mallika Pal a , Biswanath Paul a , Tarak Nath Saha a , Ashok Maiti b a b
Department of Pathology, Midnapore Medical College & Hospital, Paschim Medinipur, West Bengal, India Cancer Detection Centre, Midnapore Medical College & Hospital, Paschim Medinipur, West Bengal, India
a r t i c l e
i n f o
Article history: Received 15 September 2012 Received in revised form 22 December 2012 Accepted 7 January 2013 Available online 23 January 2013 Keywords: Goblet cell carcinoid Appendicular carcinoid Appendicular tumor
a b s t r a c t INTRODUCTION: The goblet cell carcinoid, a rare tumor of the appendix, is a separate entity from adenocarcinoma and carcinoid tumors. PRESENTATION OF CASE: We report a case of goblet cell carcinoid in our institute who presented with acute abdominal symptoms simulating acute appendicitis. DISCUSSION: Goblet cell carcinoid is a rare neoplasm with distinct histological and clinical features. The diagnosis is essentially made on histological grounds. Still the exact biological behavior of this tumor is uncertain. CONCLUSION: Considering the difficulty of clinical suspicion of this tumor, presenting as appendicitis and incidentally found during appendectomies, we review the goblet cell carcinoid of the appendix using an illustrative case report. © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
1. Introduction 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 neoplasm of the vermiform appendix, is a separate entity from adenocarcinoma, and, carcinoid tumors were first recognized in 1974.1 It has, however, been described under a number of different names, such as mucinous or mucin producing carcinoid,2,3 adenocarcinoid,3,4 intermediate type of carcinoid,5 and crypt cell carcinoma.6 All names except GCC have been omitted from the current World Health Organization (WHO) classification. The exact biological behavior of this tumor is uncertain. We discuss, through the use of a case report, the histomorphologic and immunohistochemical features of goblet cell carcinoid of the appendix. 2. Case report A 31-year-old man was admitted with a 24-h history of right iliac fossa abdominal pain associated with nausea and vomiting. There was no history of diarrhea or weight loss, and no family history of inflammatory bowel disease. He described a 1-year history of right iliac fossa pain, colicky in nature, lasting for 3–4 days at a time and recurring every 3 months. This was his second hospital admission with similar symptoms, the first episode settling with conservative management. On retrospective questioning he denied any symptoms suggestive of carcinoid syndrome.
On examination he was apyrexic with rebound tenderness in the right iliac fossa. Blood investigations revealed a white cell count of 17.5 × 109 /L and a C-reactive protein of 170 mg/L. Abdominal sonography was performed in view of the recurrent nature of the pain and the possibility of Crohn’s disease. This showed multiple fluid filled loops of bowel in the right iliac fossa but no direct visualization of the appendix and no thickened loops of small bowel. Following a short period of observation appendiectomy was performed, which confirmed an acutely inflamed appendix with purulent free fluid in the pelvis. There were no post-operative complications. Histopathologically acute appendicitis was confirmed. In addition, within the tip of the appendix there was a 4 mm indurated area (Fig. 1) that is, tumor composed of goblet cells arranged in clusters (nests) (Fig. 2A), with a bland infiltrative pattern (Fig. 2B) similar to that typical of carcinoid tumor and individual cells with eosinophilic and focally granular cytoplasm (Fig. 2C) with PAS positivity (periodic acid-Schiff stain) (Fig. 3A). The tumor extended through the muscularis propria of the appendix into serosal fat, reaching 1.5 mm from the serosal surface. The tumor was positive with the epithelial markers CK-20, CEA and neuroendocrine marker chromogranin (Fig. 3B), neuron specific enolase (NSE) (Fig. 3C). Overall the histological and immunohistochemical features were those of a goblet cell carcinoid tumor of the appendix tip with coexisting acute appendicitis. Then the follow-up of the patient was done till date the post operative period is uneventful. 3. Discussion
∗ Corresponding author at: 54/2/G, Feeder Road, P.O. Belgharia, 700056 Kolkata, West Bengal, India. Tel.: +91 9874174040. E-mail address: [email protected] (B. Mitra).
GCC accounts for less than 5% of primary tumors of the appendix.7 It shows equal sex predilection with higher incidence among white race.1 Aizawa et al. explained that the mean age for
2210-2612/$ – see front matter © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijscr.2013.01.007
CASE REPORT – OPEN ACCESS B. Mitra et al. / International Journal of Surgery Case Reports 4 (2013) 334–337
Fig. 1. Gross picture of the specimen.
GCC is 58.8 years, between malignant carcinoid (38 years) and mucinous adenocarcinoma (60 years).1 The age incidence of our case is of lower age group. The diagnosis of goblet cell carcinoid of the appendix is essentially made on histological grounds. Usually there were no features in the clinical history or the macroscopic appearance which suggested the diagnosis to the surgeon or pathologist. The diagnosis is only made therefore, after careful histological-examination of an appendicectomy specimen, and a decision then has to be made as to whether further treatment is necessary. Most of the patients present with signs and symptoms of an acute appendicitis due to luminal obstruction.8 The tumor cells proliferate sparsely and do not form nodules leading to diffuse thickening, fibrous
335
proliferation, and contraction of the appendiceal lumen, leading to appendicitis. Other manifestations include asymptomatic patients, intussusception, a palpable mass, gastrointestinal bleeding, chronic intermittent lower abdominal pain, and secondary genitourinary complications.9 Sometimes mucocele may be associated.10 A very rare complication is appendico-vesical fistula. Our reported case did not lead to any complication, neither had features of carcinoid syndrome. The white blood cell count exhibits neutrophilic leukocytosis associated with, a “shift to the left”.8 Generally, c-reactive protein is slightly elevated.10 Urinary 5-hydroxyindoleacetic acid (5-HIAA) level is mostly within normal limits. Sonography of the abdomen shows dilated small bowel loops with fluid levels when obstruction occurs.11 Cross-sectional imaging with CT is the technique of choice for any suspected appendiceal mass where GCC shows an infiltrative nature with mild but diffuse mural thickening. In our case all the clinic-laboratory parameters are indicative of an acute abdomen. Previous authors have noted the more aggressive behavior of goblet cell carcinoid tumors compared with simple appendiceal carcinoids.12 Regarding the histogenesis although GCC was previously considered a variant of carcinoid tumor, current evidence suggests that GCC is a distinct tumor with a histogenesis different from that of typical carcinoid. The nests of goblet cells are larger than normal12 arising from a pluripotent cell (stem cell) as intestinal APUD cell with endodermal origin with divergent neuroendocrine and mucinous differentiation.13 The two types of granules (neuroendocrine and mucinous) that normally exist in GCC cells are not mixed with one another.14 Because of copious production of acid mucin, the cells are strongly positive for mucicarmine, periodic acid-Schiff diastase, and alcian blue.15 Because GCC is crypt cells derived, immunohistochemically they show
Fig. 2. The tumor composed of goblet cells arranged in clusters (nests) in submucosa [(A) H&E stain 10×], with a bland infiltrative pattern [(B) H&E stain 10×]. The individual cells having eosinophilic, vacuolated and focally granular cytoplasm [(C) H&E stain 40×].
CASE REPORT – OPEN ACCESS 336
B. Mitra et al. / International Journal of Surgery Case Reports 4 (2013) 334–337
Fig. 3. The cells showing cytoplasmic periodic acid-Schiff positivity [(A) PAS stain 40×]. The cells showing chromogranin [(B) 40×] and neuron specific enolase [(C) 40×] positivity.
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.10,16 For the neuroendocrine granules in the cytoplasm, the cells are reactive for NSE, chromogranin A, Synaptophysin, Gerimelius stain, Fontana-Masson stain, serotonin, substance P, and S-100 protein. GCCs are derived from undifferentiated stem cells and are different from typical carcinoid that originates from endocrine cells in the mucosal stroma. 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. Macroscopically, in most cases, there is no well-defined mass areas of indurations in the wall or stenosis of the lumen with diffuse fibrous thickening draw attention to the possibility of tumor.12 There are several important differences between carcinoid tumor and goblet cell carcinoids: while conventional carcinoids are strongly NSE reactive, goblet cell carcinoids contain weak NSE reactive endocrine cells, few APUDcells and stain positive for lysozyme, secretory component (SC) and IgA.6 Here in our case the tumor shows weak chromogranin reactivity. The hallmark of GCC is the presence of individual glands separated by smooth muscle and the lining cells contain intracytoplasmic mucin.17 In our case this is evident in PAS stained slide (Fig. 4). Unless perforation occurred, the outer muscular coats remain well preserved. Others reported 70% distal appendiceal18 and 50% serosal or mesoappendiceal involvement with 60% cases where lymph nodes are spared.1 Lack of significant cytologic atypia, necrosis, tissue destruction, and lack of a adenomatous or in situ carcinomatous component are features used to differentiate the GCC from mucinous or signet ring cell carcinoma. In our case all the
features such as cytologic atypia, necrosis, adenomatous and in situ carcinomatous component are lacking that helps to distinguish it from adenocarcinoma of appendix. The site of the tumor within the appendix is not important for the choice of treatment.19 In general, therapy is surgical. Even though GCC has a more aggressive phenotype than benign carcinoid tumors, the prognosis is generally good and remains the treatment of choice in the majority of patients. In some patients more radical procedure is indicated especially in diffuse appendiceal involvement.8,13 Recently Varisco et al. emphasized that in patients with no concomitant caecal involvement and low-grade tumor’s histology; a simple appendectomy is enough which was followed in our case. Peritoneal carcinomatosis from GCC origin is as invasive as peritoneal surface malignancy from colorectal adenocarcinoma. In such cases, complete or near-complete surgical removal, if possible, should be considered for cytoreduction in combination with intraperitoneal chemotherapy.20 GCCs metastasize in 15–30% of cases, particularly in higher age group, compared to 2–5% in appendiceal carcinoids7 to the ovaries, pelvis, abdominal cavity, rib, vertebra and lymph nodes through lymphatic vessels, trans-celomic and intraperitoneal invasion.16 However, hematogenous metastasis to the liver or other distant organs is rare. The ovary is the most common site of metastasis and metastatic lesions sometimes show a histological picture of mucin-producing adenocarcinoma.21 The prognosis of these tumors is estimated to be somewhere between carcinoids and well-differentiated adenocarcinoma of the appendix.3 Prognosis is good except in those patients who present with the more virulent form, delayed local recurrence, lung metastases or dual neoplasia, for example, GCC/epithelial neoplasia.
CASE REPORT – OPEN ACCESS B. Mitra et al. / International Journal of Surgery Case Reports 4 (2013) 334–337
4. Conclusion GCC of the appendix is a rare entity. The clinical manifestations vary from an asymptomatic one to one with metastatic features. In “suspected appendicitis” presented with or without mass requiring surgery, GCC should be considered as differential diagnosis. Histopathologial study is essential to arrive at conclusion and to study its biological behavior. Conflict of interest statement None. Funding The source of funding was Institutional funds of Midnapore Medical College & Hospital, Paschim Medinipur. Ethical approval Written informed consent was obtained from the patient for publication of this case report and accompanying images. Author contributions BM and MP collected and analyzed the patient’s data. BM and BP prepared the manuscript. BM, AM performed the histological examination. BM and MP interpreted the Immunohistochemical slides. TS has supervised all the work and final correction of the manuscript done by him. All the authors read and approved the final manuscript. References 1. McCusker ME, Cote 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.
337
2. Klein HZ. Mucinous carcinoid tumour of the vermiform appendix. Cancer 1974;33:770–7. 3. Warkel RL, Cooper PH, Helwig EB. Adenocarcinoid, a mucin producing tumour of the appendix. A study of 39 cases. Cancer 1978;42:2781–93. 4. Olsson B. Ljungberg 0. Adenocarcinoid of the vermiform appendix. Virchows Archiv [Pathological Anatomy] 1980;386:201–10. 5. Gagne F, Fortin P, Dufour V, Dulage C. Tumeurs del’appendice associant des caracteres histologiques de carcinoideet de’adenocarcinome. Annals of Anatomy Pathological 1969;14:393–406. 6. Isaacson P. Crypt cell carcinoma of the appendix (so-called adenocarcinoid tumour). American Journal of Surgical Pathology 1981;5:213–24. 7. Gallegos NC, Milroy C, Linehan IP, Boulos PB. Crypt cell carcinoma of the appendix. European Journal of Surgical Oncology 1992;18:386–7. 8. Berardi RS, Lee SS, Chen HP. Goblet cell carcinoids of the appendix. Surgery, Gynecology and Obstetrics 1988;167:81–6. 9. Chen V, Qizilbash AH. Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature. Archives of Pathology and Laboratory Medicine 1979;103:180–2. 10. Kuroda N, Mizushima S, Guo L, Jin Y, Tao L, Miyazaki E, et al. Goblet cell carcinoid of the appendix: investigation of the expression of beta-catenin and E-cadherin. Pathology International 2001;51:283–7. 11. Goede AC, Caplin ME, Winslet MC. Carcinoid tumor of the appendix. British Journal of Surgery 2003;90:1317–22. 12. Subbuswamy SG, Gibbs NM, Ross CF, Morson BC. Goblet cell carcinoid of the appendix. Cancer 1974;34:338–44. 13. Butler JA, Houshiar A, Lin F, Wilson SE. Goblet cell carcinoid of the appendix. American Journal of Surgery 1994;168:685–7. 14. Abt AB, Carter SL. Goblet cell carcinoid of the appendix. An ultrastructural and histochemical study. Archives of Pathology and Laboratory Medicine 1976;100:301–6. 15. Kanthan R, Saxena A, Kanthan SC. Goblet cell carcinoids of the appendix: immunophenotype and ultrastructural study. Archives of Pathology and Laboratory Medicine 2001;125:386–90. 16. Anderson NH, Somerville JE, Johnston CF, Hayes DM, Buchanan KD, Sloan JM. Appendiceal goblet cell carcinoids: a clinico-pathological and immunohistochemical study. Histopathology 1991;18:61–5. 17. Burke AP, Sobin LH, Federspiel BH, Shekitka KM, Helwig EB. Goblet cell carcinoids and related tumors of the vermiform appendix. American Journal of Clinical Pathology 1990;94:27–35. 18. Park K, Blessing K, Kerr K, Chetty U, Gilmour H. Goblet cell carcinoid of the appendix. Gut 1990;31:322–4. 19. Larsen SG, Nilssen A, Helseth A, Bohler P, Giercksky KE. Invagination of the appendix with carcinoid tumor. European Journal of Surgery 1999;165:993–7. 20. Mahteme H, Sugarbaker PH. Treatment of peritoneal carcinomatosis from adenocarcinoid of appendiceal origin. British Journal of Surgery 2004;91:1168–73. 21. Ikeda E, Tsutsumi Y, Yoshida H, Yanagi K. Goblet cell carcinoid of the vermiform appendix with ovarian metastasis mimicking mucinous cystadenocarcinoma. Acta Pathologica Japonica 1991;41:455–60.
Open Access This article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, which permits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Contents lists available at SciVerse ScienceDirect
International Journal of Surgery Case Reports journal homepage: www.elsevier.com/locate/ijscr
Goblet cell carcinoid of appendix: A rare case with literature review Bhaskar Mitra a,∗ , Mallika Pal a , Biswanath Paul a , Tarak Nath Saha a , Ashok Maiti b a b
Department of Pathology, Midnapore Medical College & Hospital, Paschim Medinipur, West Bengal, India Cancer Detection Centre, Midnapore Medical College & Hospital, Paschim Medinipur, West Bengal, India
a r t i c l e
i n f o
Article history: Received 15 September 2012 Received in revised form 22 December 2012 Accepted 7 January 2013 Available online 23 January 2013 Keywords: Goblet cell carcinoid Appendicular carcinoid Appendicular tumor
a b s t r a c t INTRODUCTION: The goblet cell carcinoid, a rare tumor of the appendix, is a separate entity from adenocarcinoma and carcinoid tumors. PRESENTATION OF CASE: We report a case of goblet cell carcinoid in our institute who presented with acute abdominal symptoms simulating acute appendicitis. DISCUSSION: Goblet cell carcinoid is a rare neoplasm with distinct histological and clinical features. The diagnosis is essentially made on histological grounds. Still the exact biological behavior of this tumor is uncertain. CONCLUSION: Considering the difficulty of clinical suspicion of this tumor, presenting as appendicitis and incidentally found during appendectomies, we review the goblet cell carcinoid of the appendix using an illustrative case report. © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
1. Introduction 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 neoplasm of the vermiform appendix, is a separate entity from adenocarcinoma, and, carcinoid tumors were first recognized in 1974.1 It has, however, been described under a number of different names, such as mucinous or mucin producing carcinoid,2,3 adenocarcinoid,3,4 intermediate type of carcinoid,5 and crypt cell carcinoma.6 All names except GCC have been omitted from the current World Health Organization (WHO) classification. The exact biological behavior of this tumor is uncertain. We discuss, through the use of a case report, the histomorphologic and immunohistochemical features of goblet cell carcinoid of the appendix. 2. Case report A 31-year-old man was admitted with a 24-h history of right iliac fossa abdominal pain associated with nausea and vomiting. There was no history of diarrhea or weight loss, and no family history of inflammatory bowel disease. He described a 1-year history of right iliac fossa pain, colicky in nature, lasting for 3–4 days at a time and recurring every 3 months. This was his second hospital admission with similar symptoms, the first episode settling with conservative management. On retrospective questioning he denied any symptoms suggestive of carcinoid syndrome.
On examination he was apyrexic with rebound tenderness in the right iliac fossa. Blood investigations revealed a white cell count of 17.5 × 109 /L and a C-reactive protein of 170 mg/L. Abdominal sonography was performed in view of the recurrent nature of the pain and the possibility of Crohn’s disease. This showed multiple fluid filled loops of bowel in the right iliac fossa but no direct visualization of the appendix and no thickened loops of small bowel. Following a short period of observation appendiectomy was performed, which confirmed an acutely inflamed appendix with purulent free fluid in the pelvis. There were no post-operative complications. Histopathologically acute appendicitis was confirmed. In addition, within the tip of the appendix there was a 4 mm indurated area (Fig. 1) that is, tumor composed of goblet cells arranged in clusters (nests) (Fig. 2A), with a bland infiltrative pattern (Fig. 2B) similar to that typical of carcinoid tumor and individual cells with eosinophilic and focally granular cytoplasm (Fig. 2C) with PAS positivity (periodic acid-Schiff stain) (Fig. 3A). The tumor extended through the muscularis propria of the appendix into serosal fat, reaching 1.5 mm from the serosal surface. The tumor was positive with the epithelial markers CK-20, CEA and neuroendocrine marker chromogranin (Fig. 3B), neuron specific enolase (NSE) (Fig. 3C). Overall the histological and immunohistochemical features were those of a goblet cell carcinoid tumor of the appendix tip with coexisting acute appendicitis. Then the follow-up of the patient was done till date the post operative period is uneventful. 3. Discussion
∗ Corresponding author at: 54/2/G, Feeder Road, P.O. Belgharia, 700056 Kolkata, West Bengal, India. Tel.: +91 9874174040. E-mail address: [email protected] (B. Mitra).
GCC accounts for less than 5% of primary tumors of the appendix.7 It shows equal sex predilection with higher incidence among white race.1 Aizawa et al. explained that the mean age for
2210-2612/$ – see front matter © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijscr.2013.01.007
CASE REPORT – OPEN ACCESS B. Mitra et al. / International Journal of Surgery Case Reports 4 (2013) 334–337
Fig. 1. Gross picture of the specimen.
GCC is 58.8 years, between malignant carcinoid (38 years) and mucinous adenocarcinoma (60 years).1 The age incidence of our case is of lower age group. The diagnosis of goblet cell carcinoid of the appendix is essentially made on histological grounds. Usually there were no features in the clinical history or the macroscopic appearance which suggested the diagnosis to the surgeon or pathologist. The diagnosis is only made therefore, after careful histological-examination of an appendicectomy specimen, and a decision then has to be made as to whether further treatment is necessary. Most of the patients present with signs and symptoms of an acute appendicitis due to luminal obstruction.8 The tumor cells proliferate sparsely and do not form nodules leading to diffuse thickening, fibrous
335
proliferation, and contraction of the appendiceal lumen, leading to appendicitis. Other manifestations include asymptomatic patients, intussusception, a palpable mass, gastrointestinal bleeding, chronic intermittent lower abdominal pain, and secondary genitourinary complications.9 Sometimes mucocele may be associated.10 A very rare complication is appendico-vesical fistula. Our reported case did not lead to any complication, neither had features of carcinoid syndrome. The white blood cell count exhibits neutrophilic leukocytosis associated with, a “shift to the left”.8 Generally, c-reactive protein is slightly elevated.10 Urinary 5-hydroxyindoleacetic acid (5-HIAA) level is mostly within normal limits. Sonography of the abdomen shows dilated small bowel loops with fluid levels when obstruction occurs.11 Cross-sectional imaging with CT is the technique of choice for any suspected appendiceal mass where GCC shows an infiltrative nature with mild but diffuse mural thickening. In our case all the clinic-laboratory parameters are indicative of an acute abdomen. Previous authors have noted the more aggressive behavior of goblet cell carcinoid tumors compared with simple appendiceal carcinoids.12 Regarding the histogenesis although GCC was previously considered a variant of carcinoid tumor, current evidence suggests that GCC is a distinct tumor with a histogenesis different from that of typical carcinoid. The nests of goblet cells are larger than normal12 arising from a pluripotent cell (stem cell) as intestinal APUD cell with endodermal origin with divergent neuroendocrine and mucinous differentiation.13 The two types of granules (neuroendocrine and mucinous) that normally exist in GCC cells are not mixed with one another.14 Because of copious production of acid mucin, the cells are strongly positive for mucicarmine, periodic acid-Schiff diastase, and alcian blue.15 Because GCC is crypt cells derived, immunohistochemically they show
Fig. 2. The tumor composed of goblet cells arranged in clusters (nests) in submucosa [(A) H&E stain 10×], with a bland infiltrative pattern [(B) H&E stain 10×]. The individual cells having eosinophilic, vacuolated and focally granular cytoplasm [(C) H&E stain 40×].
CASE REPORT – OPEN ACCESS 336
B. Mitra et al. / International Journal of Surgery Case Reports 4 (2013) 334–337
Fig. 3. The cells showing cytoplasmic periodic acid-Schiff positivity [(A) PAS stain 40×]. The cells showing chromogranin [(B) 40×] and neuron specific enolase [(C) 40×] positivity.
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.10,16 For the neuroendocrine granules in the cytoplasm, the cells are reactive for NSE, chromogranin A, Synaptophysin, Gerimelius stain, Fontana-Masson stain, serotonin, substance P, and S-100 protein. GCCs are derived from undifferentiated stem cells and are different from typical carcinoid that originates from endocrine cells in the mucosal stroma. 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. Macroscopically, in most cases, there is no well-defined mass areas of indurations in the wall or stenosis of the lumen with diffuse fibrous thickening draw attention to the possibility of tumor.12 There are several important differences between carcinoid tumor and goblet cell carcinoids: while conventional carcinoids are strongly NSE reactive, goblet cell carcinoids contain weak NSE reactive endocrine cells, few APUDcells and stain positive for lysozyme, secretory component (SC) and IgA.6 Here in our case the tumor shows weak chromogranin reactivity. The hallmark of GCC is the presence of individual glands separated by smooth muscle and the lining cells contain intracytoplasmic mucin.17 In our case this is evident in PAS stained slide (Fig. 4). Unless perforation occurred, the outer muscular coats remain well preserved. Others reported 70% distal appendiceal18 and 50% serosal or mesoappendiceal involvement with 60% cases where lymph nodes are spared.1 Lack of significant cytologic atypia, necrosis, tissue destruction, and lack of a adenomatous or in situ carcinomatous component are features used to differentiate the GCC from mucinous or signet ring cell carcinoma. In our case all the
features such as cytologic atypia, necrosis, adenomatous and in situ carcinomatous component are lacking that helps to distinguish it from adenocarcinoma of appendix. The site of the tumor within the appendix is not important for the choice of treatment.19 In general, therapy is surgical. Even though GCC has a more aggressive phenotype than benign carcinoid tumors, the prognosis is generally good and remains the treatment of choice in the majority of patients. In some patients more radical procedure is indicated especially in diffuse appendiceal involvement.8,13 Recently Varisco et al. emphasized that in patients with no concomitant caecal involvement and low-grade tumor’s histology; a simple appendectomy is enough which was followed in our case. Peritoneal carcinomatosis from GCC origin is as invasive as peritoneal surface malignancy from colorectal adenocarcinoma. In such cases, complete or near-complete surgical removal, if possible, should be considered for cytoreduction in combination with intraperitoneal chemotherapy.20 GCCs metastasize in 15–30% of cases, particularly in higher age group, compared to 2–5% in appendiceal carcinoids7 to the ovaries, pelvis, abdominal cavity, rib, vertebra and lymph nodes through lymphatic vessels, trans-celomic and intraperitoneal invasion.16 However, hematogenous metastasis to the liver or other distant organs is rare. The ovary is the most common site of metastasis and metastatic lesions sometimes show a histological picture of mucin-producing adenocarcinoma.21 The prognosis of these tumors is estimated to be somewhere between carcinoids and well-differentiated adenocarcinoma of the appendix.3 Prognosis is good except in those patients who present with the more virulent form, delayed local recurrence, lung metastases or dual neoplasia, for example, GCC/epithelial neoplasia.
CASE REPORT – OPEN ACCESS B. Mitra et al. / International Journal of Surgery Case Reports 4 (2013) 334–337
4. Conclusion GCC of the appendix is a rare entity. The clinical manifestations vary from an asymptomatic one to one with metastatic features. In “suspected appendicitis” presented with or without mass requiring surgery, GCC should be considered as differential diagnosis. Histopathologial study is essential to arrive at conclusion and to study its biological behavior. Conflict of interest statement None. Funding The source of funding was Institutional funds of Midnapore Medical College & Hospital, Paschim Medinipur. Ethical approval Written informed consent was obtained from the patient for publication of this case report and accompanying images. Author contributions BM and MP collected and analyzed the patient’s data. BM and BP prepared the manuscript. BM, AM performed the histological examination. BM and MP interpreted the Immunohistochemical slides. TS has supervised all the work and final correction of the manuscript done by him. All the authors read and approved the final manuscript. References 1. McCusker ME, Cote 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.
337
2. Klein HZ. Mucinous carcinoid tumour of the vermiform appendix. Cancer 1974;33:770–7. 3. Warkel RL, Cooper PH, Helwig EB. Adenocarcinoid, a mucin producing tumour of the appendix. A study of 39 cases. Cancer 1978;42:2781–93. 4. Olsson B. Ljungberg 0. Adenocarcinoid of the vermiform appendix. Virchows Archiv [Pathological Anatomy] 1980;386:201–10. 5. Gagne F, Fortin P, Dufour V, Dulage C. Tumeurs del’appendice associant des caracteres histologiques de carcinoideet de’adenocarcinome. Annals of Anatomy Pathological 1969;14:393–406. 6. Isaacson P. Crypt cell carcinoma of the appendix (so-called adenocarcinoid tumour). American Journal of Surgical Pathology 1981;5:213–24. 7. Gallegos NC, Milroy C, Linehan IP, Boulos PB. Crypt cell carcinoma of the appendix. European Journal of Surgical Oncology 1992;18:386–7. 8. Berardi RS, Lee SS, Chen HP. Goblet cell carcinoids of the appendix. Surgery, Gynecology and Obstetrics 1988;167:81–6. 9. Chen V, Qizilbash AH. Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature. Archives of Pathology and Laboratory Medicine 1979;103:180–2. 10. Kuroda N, Mizushima S, Guo L, Jin Y, Tao L, Miyazaki E, et al. Goblet cell carcinoid of the appendix: investigation of the expression of beta-catenin and E-cadherin. Pathology International 2001;51:283–7. 11. Goede AC, Caplin ME, Winslet MC. Carcinoid tumor of the appendix. British Journal of Surgery 2003;90:1317–22. 12. Subbuswamy SG, Gibbs NM, Ross CF, Morson BC. Goblet cell carcinoid of the appendix. Cancer 1974;34:338–44. 13. Butler JA, Houshiar A, Lin F, Wilson SE. Goblet cell carcinoid of the appendix. American Journal of Surgery 1994;168:685–7. 14. Abt AB, Carter SL. Goblet cell carcinoid of the appendix. An ultrastructural and histochemical study. Archives of Pathology and Laboratory Medicine 1976;100:301–6. 15. Kanthan R, Saxena A, Kanthan SC. Goblet cell carcinoids of the appendix: immunophenotype and ultrastructural study. Archives of Pathology and Laboratory Medicine 2001;125:386–90. 16. Anderson NH, Somerville JE, Johnston CF, Hayes DM, Buchanan KD, Sloan JM. Appendiceal goblet cell carcinoids: a clinico-pathological and immunohistochemical study. Histopathology 1991;18:61–5. 17. Burke AP, Sobin LH, Federspiel BH, Shekitka KM, Helwig EB. Goblet cell carcinoids and related tumors of the vermiform appendix. American Journal of Clinical Pathology 1990;94:27–35. 18. Park K, Blessing K, Kerr K, Chetty U, Gilmour H. Goblet cell carcinoid of the appendix. Gut 1990;31:322–4. 19. Larsen SG, Nilssen A, Helseth A, Bohler P, Giercksky KE. Invagination of the appendix with carcinoid tumor. European Journal of Surgery 1999;165:993–7. 20. Mahteme H, Sugarbaker PH. Treatment of peritoneal carcinomatosis from adenocarcinoid of appendiceal origin. British Journal of Surgery 2004;91:1168–73. 21. Ikeda E, Tsutsumi Y, Yoshida H, Yanagi K. Goblet cell carcinoid of the vermiform appendix with ovarian metastasis mimicking mucinous cystadenocarcinoma. Acta Pathologica Japonica 1991;41:455–60.
Open Access This article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, which permits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.