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CASE REPORT  
Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 376-378
Lipid-rich carcinoid of the appendix: A case report with review of literature


Department of Pathology, Gujarat Adani Institute of Medical Sciences, Bhuj, Kachchh, Gujarat, India

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Date of Submission27-Jul-2020
Date of Decision14-Aug-2020
Date of Acceptance15-Oct-2020
Date of Web Publication9-Apr-2021
 

   Abstract 


The carcinoids are the most frequent tumors arising from the appendix, in majority of the cases, these are asymptomatic and are discovered after appendectomy. The lipid-rich carcinoid, also known as clear cell carcinoid; is histologically characterized by the presence of clear vacuoles in the cytoplasm of tumor cells. Only 24 cases of lipid-rich carcinoid of the appendix are described in the English literature, and there is no report of this entity in the Indian literature. In this report we describe a first case of lipid-rich carcinoid of the appendix in India and also present a review of the literature.

Keywords: Appendix, carcinoid, clear-cell carcinoid, lipid-rich carcinoid

How to cite this article:
Lanjewar DN, Parmar RA, Sharma B, Thacker M, Upadhyay JS. Lipid-rich carcinoid of the appendix: A case report with review of literature. Indian J Pathol Microbiol 2021;64:376-8

How to cite this URL:
Lanjewar DN, Parmar RA, Sharma B, Thacker M, Upadhyay JS. Lipid-rich carcinoid of the appendix: A case report with review of literature. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 8];64:376-8. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/376/313305





   Introduction Top


Well-differentiated neuroendocrine tumors, traditionally referred to as carcinoids, are the commonest neoplasms of the appendix, comprising over 50% of appendiceal neoplasms. The typical morphologic features of carcinoid includes proliferation of small, uniform cells arranged in the solid nests with peripheral-cell palisading and finely granulated eosinophilic cytoplasm and nuclei with coarse chromatin. In addition to the appendix, the lipid-rich change has been described in the neuroendocrine tumors in pancreas, stomach, gallbladder, and lung.[1],[2],[3],[4] In this report, we describe the first case of lipid-rich carcinoid of the appendix in India.


   Case Report Top


A 27-year-old female presented with complaints of fever, vomiting and pain in right iliac fossa of 2 days duration. Patient did not have history of headache, vision problems, problems with balance and walking, hypertension, flank pain and hematuria. Laboratory investigations showed hemoglobin of 7.8 gm%, total leucocyte count 7000/cu mm and differential leucocyte count; neutrophils (61%), lymphocytes (29%), eosinophils (02%) and monocytes (08%). The ultrasonography showed a blind ended aperistaltic noncompressible appendix. Clinically patient was diagnosed as appendicitis for which appendectomy was performed and resected appendix was received for histopathological evaluation. The specimen of appendix measured 3.5 cm. in length, the distal end of it showed a single, yellowish, well-circumscribed tumor measuring 2 cm ×0.5 cm in diameter near the tip [Figure 1]a. Microscopic examination of appendicular tumor showed proliferation of small, uniform cells arranged in solid nests and trabeculae with peripheral palisading [Figure 1]b. The nuclei of these tumor cells were round, had finely granular chromatin and inconspicuous nucleoli. The cytoplasm of 100% of tumor cells showed numerous small, round clear vacuoles (microvacuolization), having distinct boundaries [Figure 1]c. The tumor cells showed infiltration up to submucosa; however, there was no evidence of necrosis or lymphovascular invasion. The periodic acid Schiff (PAS) stain did not show any PAS positive material in the cytoplasm of the tumor cells. Immunohistochemistry (IHC) showed diffuse intracytoplasmic positivity for chromogranin A [Figure 1]d, and synaptophysin [Figure 1]e. The tumor cells also showed CK positivity and Ki 67 proliferation index was 1%. To rule out other differential diagnosis, IHC markers such as CEA, CK, CK7, CK20 and Inhibin were performed. IHC for CK was positive and all other markers showed negative immunoreactivity. Because the whole specimen of carcinoid of appendix was embedded in paraffin, we could not do either frozen section or electron microscopic study. The rest of appendix showed features of acute appendicitis.
Figure 1: (a) Serial coronal sections of appendix shows small well circumscribed yellowish tumour, (b) Histology shows tumour composed of small uniform cells arranged in solid nests and trabeculae (H&E 100), (c) Tumour cells show numerous intracytoplasmic clear vacuoles and stippled nuclear chromatin (H&E 400), (d) IHC shows intracytoplasmic chromogranin positivity in tumour cells, (e) IHC shows intracytoplasmic synaptophysin positivity in tumour cells

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   Discussion Top


Lipid-rich carcinoid is morphologic variant of carcinoid with IHC profile and clinical behavior similar to those of classic carcinoid tumor of the appendix. Literature describes only 24 cases of lipid-rich carcinoid of the appendix, which are described in Italy (14 cases),[5],[6] Canada (7 cases),[7] Korea (2 cases)[8] and Romania (1 case)[9] [Table 1]. The age distribution in the reported cases ranged from 9 years to 65 years and their gender composition showed 10 men and 13 women, in one case gender was not known. All 24 cases had signs and symptoms of appendicitis and 13 out of 24 cases of lipid-rich carcinoid had associated appendicitis, 3 cases showed lymphoid hyperplasia in appendix, and 2 cases showed sclerosis and edema in lamina propria. Four cases of lipid rich carcinoid showed coexistent pathology such as, mucinous cystadenocarcinoma of the appendix (2 cases), adenocarcinoma of colon (1 case) and mucinous cystadenoma of ovary (1 case). The presence of intracytoplasmic lipid in carcinoid was confirmed by electron microscopic study in four reports.[5],[6],[7],[8] The electron microscopy of lipid rich carcinoid shows the presence of intracytoplasmic lipid containing vacuoles and large number of intracytoplasmic membrane bound spherical, dense core granules consistent with neurosecretory granules. The lipid vacuoles and neurosecretory granules are seen within the same cell. The mechanism leading to lipid accumulation in the cytoplasm of carcinoid is not well known. However, the proposed hypothesis suggests that it could be local factors such as inflammation which is frequently associated with appendiceal tumor altering fat metabolism in tumor cells and leading to accumulation of triglyceride in tumor cells.[5] The differential diagnosis of lipid-rich carcinoid of the appendix are goblet cell carcinoids (GCCs), signet ring cell carcinoma of appendix and metastatic clear cell carcinomas of the kidney or ovary and clear cell carcinoid associated with Von Hippel-Lindau (VHL) disease. The GCC is usually found in mid portion of the appendix; it is whitish in color and shows mucoid appearance. Histologically GCC shows nests and clusters of goblet cells which are embedded in dense collagen. The nuclei of the tumor cells are located at the base of the cells due to presence of large cytoplasmic vacuoles. PAS and mucicarmine stains and CEA are consistently positive in GCC and tumor cells show patchy immunoreactivity for neuroendocrine marker. In the present case diffuse positivity for neuroendocrine markers and negativity for PAS and CEA rules out the possibility of GCCs. The distinction of classic lipid rich carcinoid from GCCs is important from a therapeutic point because GCC has worst prognosis and needs to be treated with right hemicolectomy.[10] The another differential diagnosis that needs to be ruled out is the signet ring cell carcinoma of appendix, which is characterized by presence of sheets of tumor cells having peripherally pushed nuclei and large amount of cytoplasmic mucin. The tumor cells show cytoplasmic positivity with PAS stain and CK7. In the present case PAS stain was negative and IHC for CK 7 was also negative, this rules out the diagnosis of signet ring cell carcinoma of the appendix. The distinction of lipid rich carcinoid from metastatic renal cell carcinoma (RCC) is easy as tumor cells of RCC are large, nuclei are centrally located, and the cytoplasm is clear or granular. The clear cells of renal cell carcinoma do not show microvacuolization in their cytoplasm and is negative for neuroendocrine, CK7, CK20, and inhibin markers. In the present case neuroendocrine markers were diffusely positive, CK7, CK20, and inhibin were negative; this rules out a possibility of metastasis of renal cell carcinoma. A clear cell variant of ovarian carcinoma shows tubulo-cystic, papillary configuration and solid pattern and the tumor cells are large, cytoplasm is clear and PAS positive and also show positivity for CK7 and is negative for neuroendocrine markers. In the present case neuroendocrine marker was diffusely positive and CK7 was negative; this rules out a possibility of metastasis of clear cell carcinoma of ovary.
Table 1: Published reports of lipid rich carcinoid of appendix (n=24)

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The clear cell carcinoid is also described in patients with VHL disease and therefore needs to be considered in differential diagnosis. Our patient did not have history of headache, vision problems, problems with balance and walking, hypertension, flank pain, and hematuria. The clear cell carcinoid associated with VHL disease shows Inhibin positivity.[3] In the present case IHC for Inhibin was negative, hence on clinical and on IHC study VHL disease is ruled out.


   Conclusion Top


This report describes the first case of lipid-rich variant of appendiceal carcinoid in the Indian literature. The prognostic features of lipid-rich carcinoid are not different from conventional appendiceal carcinoid. Distinguishing between a lipid-rich carcinoid and GCC or signet ring cell carcinoma of appendix and metastatic clear-cell carcinoma of kidney or ovary and clear cell carcinoid associated with VHL disease is extremely important, as prognosis and treatment differs between these types of tumors.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Singh R, Basturk O, Klimstra DS, Zamboni G, Chetty R, Hussain S, et al. Lipid-rich variant of pancreatic endocrine neoplasms. Am J Surg Pathol 2006;30:194-200.  Back to cited text no. 1
    
2.
Ordóñez NG, Mackay B, el-Naggar A, Bannayan GA, Duncan J. Clear cell carcinoid tumour of the stomach. Histopathology 1993;22:190-3.  Back to cited text no. 2
    
3.
Sinkre PA, Murakata L, Rabin L, Hoang MP, Albores-Saavedra J. Clear cell carcinoid tumor of the gallbladder: Another distinctive manifestation of von Hippel-Lindau disease. Am J Surg Pathol 2001;25:1334-9.  Back to cited text no. 3
    
4.
Gaffey MJ, Mills SE, Frierson HF Jr, Askin FB, Maygarden SJ. Pulmonary clear cell carcinoid tumor: Another entity in the differential diagnosis of pulmonary clear cell neoplasia. Am J Surg Pathol 1998;22:1020-5.  Back to cited text no. 4
    
5.
La Rosa S, Finzi G, Puppa G, Capella C. Lipid-rich variant of appendiceal well-differentiated endocrine tumor (carcinoid). Am J Clin Pathol 2010;133:809-14.  Back to cited text no. 5
    
6.
Rossi G, Nannini N, Bertolini F, Mengoli MC, Fano R, Cavazza A. Clear cell carcinoid of the appendix: An uncommon variant of lipid-rich neuroendocrine tumor with a broad differential diagnosis. Endocr Pathol 2010;21:258-62.  Back to cited text no. 6
    
7.
Chetty R, Serra S. Lipid-rich and clear cell neuroendocrine tumors ('carcinoids') of the appendix: Potential confusion with goblet cell carcinoid. Am J Surg Pathol 2010;34:401-4.  Back to cited text no. 7
    
8.
Kang GH, Lee BS, Kang DY. Clear cell carcinoid of the appendix: Report of two cases with literature review. Pathol Int 2015;65:324-8.  Back to cited text no. 8
    
9.
Andreea I, Narcis OZ, Alexandru C, Eugenia CZ, Irena AU, Ştefan IN, et al. A rare case of clear-cell carcinoid of appendix. Rom J Morphol Embryol 2017;58:1509-13.  Back to cited text no. 9
    
10.
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. 10
    

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Correspondence Address:
Dhaneshwar N Lanjewar
Prof. and Head Department of Pathology, Gujarat Adani Institute of Medical Sciences, Bhuj, Kachchh, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_894_20

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