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Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 669

An unusual case of disseminated neuroendocrine tumor presenting with generalized lymphadenopathy

1 Department of General Surgery, Kasturba Medical College, Mangalore, Manipal University, Manipal, Karnataka, India
2 Department of Pathology, Kasturba Medical College, Mangalore, Manipal University, Manipal, Karnataka, India

Date of Web Publication9-Oct-2015

Correspondence Address:
Dr. K S Karthik
Department of General Surgery, Kasturba Medical College, Manipal University, Mangalore - 575 001, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.151947

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 > Abstract 

A 64-year-old male presented to the surgical out-patient department with multiple enlarged lymph nodes in the neck and axillae. As a routine practice in India, this patient was worked up on the lines of generalized lymphadenopathy with a provisional diagnosis of tuberculosis and lymphoma. The report of fine-needle aspiration cytology (FNAC) came as a surprise and on further work-up it turned out to be that the patient had disseminated neuroendocrine tumor from an unknown primary.

Keywords: Disseminated neuroendocrine tumour, generalised lymphadenopathy, unknown primary

How to cite this article:
Karthik K S, Kini H, Kini AU, Santosh P. An unusual case of disseminated neuroendocrine tumor presenting with generalized lymphadenopathy. J Can Res Ther 2015;11:669

How to cite this URL:
Karthik K S, Kini H, Kini AU, Santosh P. An unusual case of disseminated neuroendocrine tumor presenting with generalized lymphadenopathy. J Can Res Ther [serial online] 2015 [cited 2020 Jul 16];11:669. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/669/151947

 > Introduction Top

Neuroendocrine tumors (NETs) arise from cells of the endocrine and nervous system with an incidence of 3-5 per 100,000 and prevalence of about 35 per 100,000. [1],[2] The prevalence suggests the indolent nature of this disease with the 5-year survival approaching 50%. [3] Mostly benign, rarely malignant, they present in gastrointestinal tract, lung, adrenals, and rarely metastasize to lymph nodes. NETs account for about 3% of all carcinoma of unknown primary. [4] There is no concrete information on the incidence of metastasis to neck and mediastinum as it was thought to be medically insignificant. A study by Wang YZ et al., demonstrated the incidence of such metastasis to be 8.7%, much higher than the previous assumed and accepted (3-4%) by experts in the field, though no formal large population studies were conducted to confirm this number. [5] Similarly, incidence of NET metastasizing to axilla has not been reported in any large-population studies, although some isolated cases have been reported. NETs should be included in the differential diagnosis of masses in the axillary region. [6] Here, we describe a patient who has disseminated tumor from an occult primary with visceral and multiple lymph node metastasis.

 > Case report Top

A 64-year-old male patient, chronic alcoholic, and smoker presented with swellings [Figure 1] over the left side of neck extending from angle of mandible to supraclavicular fossa (2 × 3 cms) and both axillae (5 × 3 cms in left axilla and 2 × 3 cms in right axilla) of 4-months duration, which were insidious in onset, painless, and rapidly growing. Patient had occasional episodes of breathlessness. There was no history of flushing or diarrhea. Routine laboratory investigations were normal except for hemoglobin of 9.6 gm/dl. Computerized tomography (CT) suggested multiple enlarged lymph nodes in bilateral cervical region, bilateral axillae, left supraclavicular region, and mediastinum. CT chest and abdomen revealed metastatic deposits to lung, liver, vertebra, and iliac bones. Fine-needle aspiration cytology (FNAC) from neck nodes showed poorly differentiated carcinoma. On trucut biopsy from the axillary lymph nodes, tumor cells were found to be arranged predominantly in an insular pattern separated by fibrocollagenous stroma. Tumor cells were moderately pleomorphic with scanty cytoplasm and round to oval nuclei having stippled chromatin. Occasional mitotic figures were present with no evidence of necrosis [Figure 2]. On further immunohistochemical (IHC) evaluation, the tumor showed positivity for pan-cytokeratin and chromogranin [Figure 3] but was negative for S-100. Ki 67 showed a proliferation index of 6%. Based on the histological and IHC features, a diagnosis of moderately differentiated neuroendocrine carcinoma was arrived at. Patient was treated with 6 cycles of chemotherapy with Etoposide and Cisplatin. The patient partially responded to the treatment in the initial phase. With the performance score dipping, further chemotherapy with altered or different regimen was deferred. Patient had an episode of fracture neck of femur (proved traumatic and non-pathological) 6 months ago. Currently, the patient is under regular follow-up with evidence of relapse a month ago and is undergoing palliative treatment.
Figure 1: Patient having lymphadenopathy in axilla and neck (inset)

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Figure 2: Tumor cells arranged in nests separated by fibrous septa (H and E, ×100)

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Figure 3: Immunohistochemistry for Chromogranin showing strong positivity (×400)

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 > Discussion Top

About 3-5% of all human cancers are metastatic from an unknown primary. [7],[8] The incidence of lymph node metastasis from an unknown primary NETs is less than 5% of all carcinoma arising unknown primaries. [9] Lymph node metastasis from a NET from an unknown primary is not common except for few reported instances of isolated lymph node involvement as reported by Eusebi et al. who described eight cases of neuroendocrine tumors in lymph nodes with unknown primary. [10] Presentation with generalized lymphadenopathy is almost unheard and has not been reported to the best of our knowledge.

It is indeed a challenge to diagnose and treat such a rare presentation. Non-invasive modalities like X-ray and CT should be used before proceeding to invasive modalities. Chromogranin, synaptophysin, and CD 56 (NCAM) are the reliable IHC markers to diagnose NET. [11],[12],[13]

Capella et al., probably described the most useful classification to predict prognosis of NETs originating from the gastrointestinal tract. In this revised classification for NETs of the lung, pancreas, and gut, they graded the tumor as benign, low-grade malignant, and high-grade malignant by using histological differentiation, tumor size, angioinvasion, and infiltrative growth combined with the primary tumor site and production of hormones. [14] The grade describes the biologic aggressiveness of the tumor. [15] For carcinoid tumors and PNET, the grading system is based on the rate of proliferation, which is defined by the number of mitoses per 10 high-power microscopic fields or per 2 mm 2 (mitotic rate), or as the percentage of tumor cells that stain positive for the Ki-67 antigen (Ki-67 index). [15] The 2010 World Health Organization (WHO) classification of NET is based on tumor site of origin, clinical syndrome, and differentiation. [16] The histological classification of NET including grade (G) and differentiation describes NET as well-differentiated (Low Grade G1), moderately differentiated (Intermediate Grade, G2), poorly differentiated (High Grade, G3), based on the appearance, prognosis, mitotic rate, Ki 67 index, and necrosis. [17],[18] The well-differentiated NETs were previously designated as typical (i.e., carcinoid tumor), moderately differentiated NET as atypical, and poorly differentiated NET as small cell carcinoma, large cell neuroendocrine carcinoma (NEC), or simply NEC. [17]

Cisplatin-based chemotherapy especially in combination with Etoposide is suggested for malignant neuroendocrine tumor. [19] Chemotherapy may be chosen based on the histological variant and classification of the disease. The disease progression was slow in our patient. While describing a case of carcinoid tumor, Baker S and Mukherjee A have rightly commented that the therapy with curative intention in an asymptomatic case cannot be always justified. [20] Patient's performance score and condition should also be considered as an unnecessary intervention will only result in increased morbidity and mortality.

Disseminated neuroendocrine tumor presenting with generalized lymphadenopathy is a rare case scenario. Cisplatin-based chemotherapy may show initial response in the disease and delay the progress. To continue or change the chemotherapy regimen in an asymptomatic patient is a tough call to take. In our case, the patient survived beyond 1 year without major medical intervention, although with sustainable morbidity. Following up and discussing about a patient with such a rare presentation will enhance the existing knowledge in medicine and enlighten students and practitioners alike.

 > References Top

Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after "carcinoid": Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063-72.  Back to cited text no. 1
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97:934-59.  Back to cited text no. 2
Basuroy R, Srirajaskanthan R, Ramage JK. A multimodal approach to the management of neuroendocrine tumour liver metastases. Int J Hepatol 2012;2012:819193.  Back to cited text no. 3
Gr eco AF, Hainsworth JD. Cancer of unknown primary. In: Devita Jr VT, Lawrence TS, Rosenberg SA, editors. 9 th ed. Cancer: Principles and Practice of Oncology. p. 2033-51.  Back to cited text no. 4
Wang Y, Mayhall G, Anthony L, Campeau R, Boudreaux J, Woltering E. Cervical and upper mediastinal lymph node metastasis from gastrointestinal and pancreatic neuroendocrine tumors: True incidence and management. J Am Coll Surg 2012;214:1017-22.  Back to cited text no. 5
Koo H, Sohn Y, Park Y. Sonographic appearance of a neuroendocrine tumor arising in the axilla: Case report and literature review. J Clin Ultrasound 2014;42:30-2.  Back to cited text no. 6
Pavlidis N, Briasoulis E, Hainsworth J, Greco F. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 2003;39:1990-2005.  Back to cited text no. 7
Greco F, Hainsworth J. Introduction: Unknown primary cancer. Semin Oncol 2009;36:6-7.  Back to cited text no. 8
Spigel D, Hainsworth J, Greco F. Neuroendocrine carcinoma of unknown primary site. Semin Oncol 2009;36:52-9.  Back to cited text no. 9
Eusebi V, CapellaC, Cossu A, Rosai J. Neuroendocrine carcinoma within lymph nodes in the absence of a primary tumor, with special reference to Merkel cell carcinoma. Am J Surg Pathol 1992;16:658-66.  Back to cited text no. 10
Lyda M, Weiss L. Immunoreactivity for epithelial and norendocrine antibodies is useful in the differential diagnosis of lung carcinomas. Hum Pathol 2000;31:980-7.  Back to cited text no. 11
Lantuejoul S, Moro D, Michalides RJ, Brambilla C, Brambilla E. Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol 1998;22:1267-76.  Back to cited text no. 12
Kauffman O. Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas in paraffin sections. Hum Pathol 1997;28:1373-8.  Back to cited text no. 13
Capella C, Geitz P, Hofler H, Solcia E, Klöppel G. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 1995;425:547-60.  Back to cited text no. 14
Kulke MH1, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS, et al. NANETS treatment guidelines: Well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010;39:735-52.  Back to cited text no. 15
Oberg K, Castellano D. Current knowledge on diagnosis and staging of neuroendocrine tumors. Cancer Metastasis Rev 2011;30:3-7.  Back to cited text no. 16
Klimsttra D, Modlin I, Coppola D, Lloyed RV, Suster S. The pathologic classification of neuroendocrine tumors: A review of nomenclature, grading, and staging systems. Pancreas 2010;39:707-12.  Back to cited text no. 17
Strosberg J, Nasir A, Hodul P, Kvols L. Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res 2008;2:113-25.  Back to cited text no. 18
Mitry E, Baudin E, Ducreux M, Sabourin JC, Rufie P, Aparicio T, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer 1999;81:1351-5.  Back to cited text no. 19
Baker S, Mukherjee A. Nodal metastases with unknown primary - an unusual presentation of carcinoid tumor. S D J Med 2000;53:105-9.  Back to cited text no. 20


  [Figure 1], [Figure 2], [Figure 3]


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