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A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder

A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder Hindawi Case Reports in Oncological Medicine Volume 2022, Article ID 6956046, 4 pages https://doi.org/10.1155/2022/6956046 Case Report A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder 1 2 2 3 3 Rodney E. Shackelford, Ekin Ozluk, Jehan Abdulsattar, Terry C. Lairmore, Quyen Chu, and Eric X. Wei Department of Pathology, University of South Alabama Health, Mobile, Alabama 36617, USA Department of Pathology & Translational Pathobiology, LSU Health Sciences Center Shreveport, Shreveport, Louisiana 71130, USA Department of Surgery, Louisiana State University Health Shreveport, Louisiana 71130, USA Correspondence should be addressed to Eric X. Wei; ericxwei@yahoo.com Received 1 December 2021; Revised 12 April 2022; Accepted 29 April 2022; Published 21 May 2022 Academic Editor: Ossama W. Tawfik Copyright © 2022 Rodney E. Shackelford et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is a rare malignancy which is often associated with non- LCNEC histologic components. Histologically “pure” LCNECs of the gallbladder are exceedingly rare with only 15 cases reported in the medical literature. Clinically, LCNECs present with abdominal pain and jaundice and follow an aggressive course with th patients surviving a median of 15 months following initial diagnosis. To our knowledge, we present the 16 case of a histologically pure LCNEC in a 62-year-old African American male who was successfully treated surgically. After discharge, he was subsequently lost to follow-up. Due to the extreme rarity of such disease entity, accurate diagnosis and proper management are essential for the best clinical outcome. 1. Introduction Primary neuroendocrine tumors of the gallbladder are rare, totaling only 0.5% of all neuroendocrine tumors and 2.1% of all gallbladder malignancies [2]. LCNECs were first The current World Health Organization (WHO) classifica- described in 1991 when pulmonary cases were reported tion of neuroendocrine tumors of the gallbladder includes [3]. LCNECs of the gallbladder are extremely rare and are grade I and II neuroendocrine tumors, small cell neuroendo- crine carcinoma, large cell neuroendocrine carcinoma commonly composed of neuroendocrine cells with other associated histologies, including adenocarcinoma, adenos- (LCNEC), mixed adenoneuroendocrine carcinoma, goblet quamous carcinoma, and mucinous adenocarcinoma com- cell carcinoid, and tubular carcinoid tumors [1]. Histologi- ponents [4]. LCNECs composed solely of enteroendocrine cally, neuroendocrine tumors frequently grow in trabecular features (“pure” LCNECs) are exceptionally rare, with only or organoid patterns, often with rosettes and with “salt and pepper” nuclear patterns. The more poorly differentiated 15 cases described in the medical literature [5]. Here, to th our knowledge, we describe the 16 case of a primary gall- and clinically aggressive subtypes show a high mitotic index. Neuroendocrine tumors typically show immunoreactivity bladder LCNEC composed solely of large neuroendocrine carcinoma cells. towards the neuroendocrine markers chromogranin, synaptophysin, CD56, Leu 7, and neuron-specific enolase [1–5]. LCNECs are composed of large cells that are usually 2. Case Presentation two to three times larger than those of small cell neuroendo- crine tumors and show brisk mitotic activity, with hyper- A 62-year-old African American male presented with a chromatic nuclei and prominent nucleoli [1–5]. history of acute vomiting and right upper-quadrant and 2 Case Reports in Oncological Medicine Figure 1: A noncontrast CT scan of the patient’s abdomen revealing thickening of the gallbladder wall with a possible polyp (white arrow). epigastric pain, one day before admission to the hospital. His the sixth day of hospitalization postoperatively, the patient pain had become so unbearable that he was prompted to call recovered without further complications and was sent an ambulance. The patient’s previous medical history home with scheduled follow-up. His medications included included hypertension, hyperlipidemia, atherosclerosis, treatment regimens for his hypertension, hyperlipidemia, and type II diabetes, all of which were medically managed. and diabetes without further chemotherapy. After the dis- He also had an extensive 40-year smoking history. The charge, the patient was subsequently lost to follow-up. patient did not reveal any significant family medical his- tory. His physical exam was significant for high blood 3. Discussion pressure of 190/96 mmHg and guarding on palpation of the abdomen. His serum chromogranin or other neuroen- Here, we presented a 62-year-old African American male docrine markers were not tested. Initial imaging studies with pure LCNEC of the gallbladder. The histological fea- were performed with ultrasound of the abdomen, which tures and positive immunostainings for AE1/AE3, CD56, was significant for hepatomegaly and cholelithiasis, c-kit, and NSE and high proliferation index at 95% would without evidence of cholecystitis. A noncontrast abdominal support the diagnosis of LCNEC. Negative synaptophysin CT scan was performed where stones, a possible gallblad- and chromogranin expression is unusual and may suggest der polyp, and thickening of the gallbladder wall were poor differentiation of the tumor. Negative S-100 expression identified, which were concerning for malignancy excludes a high-grade peripheral nerve sheath tumor. (Figure 1). A laparoscopic cholecystectomy was performed, Although the tumor cells express c-kit, negative DOG-1 and the gallbladder was found to be grossly distended, staining rules out an epithelioid gastrointestinal stomal partially filled with multiple multifaceted calculi, contain- tumor (GIST). The expression of c-kit in tumor cells may ing a central polypoid mass roughly 3.0 cm in size and indicate tumor origin from undifferentiated stem cells. The exhibiting focal thickening of the gallbladder wall. An fact that the tumor cells are negative for CD20 also removes attached gallbladder lymph node partially involved by the consideration of a large B cell lymphoma. Neuroendo- metastatic tumor cells was also identified. Histologically, crine tumors of the gallbladder are rare with LCNEC tumors the tumor showed extensive necrosis and large cells with of this organ being very uncommon [1, 5]. “Pure” gallblad- salt and pepper nuclei, prominent nucleoli, and a der LCNECs containing only the large cell neuroendocrine trabecular growth pattern (Figures 2(a)–2(c)). Immunohis- histology are exceedingly rare, with only 15 cases recorded tochemical staining for AE1/AE3, chromogranin, synapto- in the medical literature [5]. Neuroendocrine cells are not physin, CD20, CD56, DOG-1, Ki-67, MART-1, S-100, normally found in the gallbladder, which is a likely reason SOX-10, TTF-1, neuron-specific enolase (NSE), and c-kit why these tumors are so rare in this organ [6–8]. How these were performed on the polypoid mass. The tumor cells tumors arise in the gallbladder is unknown; however, it has were immunoreactive to CD56 (membranous), AE1/AE3, been hypothesized that these malignancies may arise from c-kit, and NSE (cytoplasmic) (Figures 2(d)–2(g)) and neg- undifferentiated stem cells or from chronic inflammation ative for CD20, chromogranin, synaptophysin, DOG-1, S- such as cholecystitis leading to intestinal or gastric metapla- 100, and other markers performed, consistent with a sia and neuroendocrine cell formation with later malignant LCNEC [1–5]. The Ki-67 immunostaining revealed a brisk transformation [5–7]. LCNECs have presented in patients miotic index with over 95% immunopositivity between the ages of 55 to 76 years, usually with symptoms (Figure 2(h)). The tumor was staged as pT3, pN1. After similar to the more common gallbladder malignancies, Case Reports in Oncological Medicine 3 (a) (b) (c) (d) (e) (f) (g) (h) Figure 2: Representative H&E sections of the gallbladder LCNEC and some of the immunostains performed. Very low-power H&E view (20x) of the LCNEC showing necrosis and tumor cells (a), low-power H&E section (40x) showing the trabecular growth pattern (b), and a middle-power view (200x) showing the neuroendocrine features of the LCNEC (c). Sections (d–h) show the CD56, AE1/AE3, c-kit, neuron-specific enolase, and Ki-67 immunostains, respectively. 4 Case Reports in Oncological Medicine literature,” World Journal of Surgical Oncology, vol. 13, no. 1, including jaundice and abdominal pain/discomfort [5]. p. 114, 2015. Common radiological findings include a mass in place of the gallbladder, focal or diffuse gallbladder wall thickening, [5] A. Tidjane, N. Boudjenan, A. Bengueddach et al., “Pure large cell neuroendocrine carcinoma of the gallbladder, is surgical and direct invasion of the tumor into the liver or metastasis relentlessness beneficial? A case report and literature review,” to the surrounding lymph nodes [1]. LCNECs are typically International Cancer Conference Journal, vol. 10, no. 2, very aggressive, with a median survival time of 15 months pp. 127–133, 2021. and with a range of 21 days to 69 months [5]. For qualifying [6] M. Murakami, K. Katayama, S. Kato et al., “Large-cell neuro- patients, optimal treatment for these tumors is complete sur- endocrine carcinoma of the common bile duct: a case report gical resection with surrounding lymph node clearance and and a review of literature,” Surgical Case Reports, vol. 2, hepatic lobectomy, with recurrences being very common no. 1, p. 141, 2016. [5]. In the event of an unresectable tumor, systemic chemo- [7] S. B. Park, S. B. Moon, Y. J. Ryu et al., “Primary large cell neu- therapy is the next treatment option, which employs the roendocrine carcinoma in the common bile duct: first Asian same platinum-based chemotherapy regimen, often with case report,” World Journal of Gastroenterology, vol. 20, radiation therapy, as is used for small cell neuroendocrine no. 47, pp. 18048–18052, 2014. carcinoma treatment [5, 8]. The efficacy of traditional che- [8] A. Iyoda, T. Makino, S. Koezuka, H. Otsuka, and Y. Hata, motherapy with additional radiotherapy remains unclear “Treatment options for patients with large cell neuroendocrine due to insensitivity of general neuroendocrine tumors to carcinoma of the lung,” General Thoracic and Cardiovascular radiotherapy; however, this is a treatment option for Surgery, vol. 62, no. 6, pp. 351–356, 2014. patients with multiple metastases or an unresectable tumor [9] I. M. Modlin, M. Kidd, I. Drozdov, Z. L. Siddique, and B. I. [9]. Recently, immunotherapy with ipilimumab and nivo- Gustafsson, “Pharmacotherapy of neuroendocrine cancers,” lumab has shown some promise in a small phase II clini- Expert Opinion Pharmacotherapy, vol. 9, no. 15, pp. 2617– cal trial treating LCNECs [10]. Due to the rarity of these 2626, 2008. tumors, especially of pure LCNECs of the gallbladder, [10] S. Patel, “A phase II basket trial of nivolumab and ipilimumab there is much that is unknown about how these extremely in rare tumors (NET cohort),” American Association of Cancer rare tumors should be treated [8, 10]. An accurate diagno- Research, vol. 79, 2019. sis of LCNEC is also essential as the treatment for these [11] S. Buscemi, E. Orlando, G. Damiano et al., ““Pure” large cell tumors is different than that used for the more common neuroendocrine carcinoma of the gallbladder. Report of a case adenocarcinomas of the gallbladder [5, 8, 11]. In conclu- and review of the literature,” International Journal of Surgery, sion, histologically pure LCNEC tumors of the gallbladder vol. 28, Supplement 1, pp. S128–S132, 2016. are exceedingly rare [5, 11]. The unique nature of this tumor requires that further studies be utilized to optimize its treatment. In particular, immune and DNA sequence analyses, multimodal treatment regimes, and immune therapies will likely play an important role in the future treatment of these rare malignancies [5, 11]. Conflicts of Interest The authors declare that there is no conflict of interest regarding the publication of this article. References [1] K. M. Eltawil, B. I. Gustafsson, M. Kidd, and I. M. Modlin, “Neuroendocrine tumors of the gallbladder,” Journal of Clini- cal Gastroenterology, vol. 44, no. 10, pp. 687–695, 2010. [2] M. Papotti, P. Cassoni, A. Sapino, G. Passarino, J. E. Krueger, and J. Albores-Saavedra, “Large cell neuroendocrine carci- noma of the gallbladder: report of two cases,” The American Journal of Surgical Pathology, vol. 24, no. 10, pp. 1424–1428, [3] W. D. Travis, R. I. Linnoila, M. G. Tsokos et al., “Neuroendo- crine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohisto- chemical, and flow cytometric study of 35 cases,” The Ameri- can Journal of Surgical Pathology, vol. 15, no. 6, pp. 529–553, [4] W. Liu, L. Wang, X. D. He, C. Feng, X. Y. Chang, and Z. H. Lu, “Mixed large cell neuroendocrine carcinoma and adenocarci- noma of the gallbladder: a case report and brief review of the http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder

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Copyright © 2022 Rodney E. Shackelford et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract

Hindawi Case Reports in Oncological Medicine Volume 2022, Article ID 6956046, 4 pages https://doi.org/10.1155/2022/6956046 Case Report A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder 1 2 2 3 3 Rodney E. Shackelford, Ekin Ozluk, Jehan Abdulsattar, Terry C. Lairmore, Quyen Chu, and Eric X. Wei Department of Pathology, University of South Alabama Health, Mobile, Alabama 36617, USA Department of Pathology & Translational Pathobiology, LSU Health Sciences Center Shreveport, Shreveport, Louisiana 71130, USA Department of Surgery, Louisiana State University Health Shreveport, Louisiana 71130, USA Correspondence should be addressed to Eric X. Wei; ericxwei@yahoo.com Received 1 December 2021; Revised 12 April 2022; Accepted 29 April 2022; Published 21 May 2022 Academic Editor: Ossama W. Tawfik Copyright © 2022 Rodney E. Shackelford et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is a rare malignancy which is often associated with non- LCNEC histologic components. Histologically “pure” LCNECs of the gallbladder are exceedingly rare with only 15 cases reported in the medical literature. Clinically, LCNECs present with abdominal pain and jaundice and follow an aggressive course with th patients surviving a median of 15 months following initial diagnosis. To our knowledge, we present the 16 case of a histologically pure LCNEC in a 62-year-old African American male who was successfully treated surgically. After discharge, he was subsequently lost to follow-up. Due to the extreme rarity of such disease entity, accurate diagnosis and proper management are essential for the best clinical outcome. 1. Introduction Primary neuroendocrine tumors of the gallbladder are rare, totaling only 0.5% of all neuroendocrine tumors and 2.1% of all gallbladder malignancies [2]. LCNECs were first The current World Health Organization (WHO) classifica- described in 1991 when pulmonary cases were reported tion of neuroendocrine tumors of the gallbladder includes [3]. LCNECs of the gallbladder are extremely rare and are grade I and II neuroendocrine tumors, small cell neuroendo- crine carcinoma, large cell neuroendocrine carcinoma commonly composed of neuroendocrine cells with other associated histologies, including adenocarcinoma, adenos- (LCNEC), mixed adenoneuroendocrine carcinoma, goblet quamous carcinoma, and mucinous adenocarcinoma com- cell carcinoid, and tubular carcinoid tumors [1]. Histologi- ponents [4]. LCNECs composed solely of enteroendocrine cally, neuroendocrine tumors frequently grow in trabecular features (“pure” LCNECs) are exceptionally rare, with only or organoid patterns, often with rosettes and with “salt and pepper” nuclear patterns. The more poorly differentiated 15 cases described in the medical literature [5]. Here, to th our knowledge, we describe the 16 case of a primary gall- and clinically aggressive subtypes show a high mitotic index. Neuroendocrine tumors typically show immunoreactivity bladder LCNEC composed solely of large neuroendocrine carcinoma cells. towards the neuroendocrine markers chromogranin, synaptophysin, CD56, Leu 7, and neuron-specific enolase [1–5]. LCNECs are composed of large cells that are usually 2. Case Presentation two to three times larger than those of small cell neuroendo- crine tumors and show brisk mitotic activity, with hyper- A 62-year-old African American male presented with a chromatic nuclei and prominent nucleoli [1–5]. history of acute vomiting and right upper-quadrant and 2 Case Reports in Oncological Medicine Figure 1: A noncontrast CT scan of the patient’s abdomen revealing thickening of the gallbladder wall with a possible polyp (white arrow). epigastric pain, one day before admission to the hospital. His the sixth day of hospitalization postoperatively, the patient pain had become so unbearable that he was prompted to call recovered without further complications and was sent an ambulance. The patient’s previous medical history home with scheduled follow-up. His medications included included hypertension, hyperlipidemia, atherosclerosis, treatment regimens for his hypertension, hyperlipidemia, and type II diabetes, all of which were medically managed. and diabetes without further chemotherapy. After the dis- He also had an extensive 40-year smoking history. The charge, the patient was subsequently lost to follow-up. patient did not reveal any significant family medical his- tory. His physical exam was significant for high blood 3. Discussion pressure of 190/96 mmHg and guarding on palpation of the abdomen. His serum chromogranin or other neuroen- Here, we presented a 62-year-old African American male docrine markers were not tested. Initial imaging studies with pure LCNEC of the gallbladder. The histological fea- were performed with ultrasound of the abdomen, which tures and positive immunostainings for AE1/AE3, CD56, was significant for hepatomegaly and cholelithiasis, c-kit, and NSE and high proliferation index at 95% would without evidence of cholecystitis. A noncontrast abdominal support the diagnosis of LCNEC. Negative synaptophysin CT scan was performed where stones, a possible gallblad- and chromogranin expression is unusual and may suggest der polyp, and thickening of the gallbladder wall were poor differentiation of the tumor. Negative S-100 expression identified, which were concerning for malignancy excludes a high-grade peripheral nerve sheath tumor. (Figure 1). A laparoscopic cholecystectomy was performed, Although the tumor cells express c-kit, negative DOG-1 and the gallbladder was found to be grossly distended, staining rules out an epithelioid gastrointestinal stomal partially filled with multiple multifaceted calculi, contain- tumor (GIST). The expression of c-kit in tumor cells may ing a central polypoid mass roughly 3.0 cm in size and indicate tumor origin from undifferentiated stem cells. The exhibiting focal thickening of the gallbladder wall. An fact that the tumor cells are negative for CD20 also removes attached gallbladder lymph node partially involved by the consideration of a large B cell lymphoma. Neuroendo- metastatic tumor cells was also identified. Histologically, crine tumors of the gallbladder are rare with LCNEC tumors the tumor showed extensive necrosis and large cells with of this organ being very uncommon [1, 5]. “Pure” gallblad- salt and pepper nuclei, prominent nucleoli, and a der LCNECs containing only the large cell neuroendocrine trabecular growth pattern (Figures 2(a)–2(c)). Immunohis- histology are exceedingly rare, with only 15 cases recorded tochemical staining for AE1/AE3, chromogranin, synapto- in the medical literature [5]. Neuroendocrine cells are not physin, CD20, CD56, DOG-1, Ki-67, MART-1, S-100, normally found in the gallbladder, which is a likely reason SOX-10, TTF-1, neuron-specific enolase (NSE), and c-kit why these tumors are so rare in this organ [6–8]. How these were performed on the polypoid mass. The tumor cells tumors arise in the gallbladder is unknown; however, it has were immunoreactive to CD56 (membranous), AE1/AE3, been hypothesized that these malignancies may arise from c-kit, and NSE (cytoplasmic) (Figures 2(d)–2(g)) and neg- undifferentiated stem cells or from chronic inflammation ative for CD20, chromogranin, synaptophysin, DOG-1, S- such as cholecystitis leading to intestinal or gastric metapla- 100, and other markers performed, consistent with a sia and neuroendocrine cell formation with later malignant LCNEC [1–5]. The Ki-67 immunostaining revealed a brisk transformation [5–7]. LCNECs have presented in patients miotic index with over 95% immunopositivity between the ages of 55 to 76 years, usually with symptoms (Figure 2(h)). The tumor was staged as pT3, pN1. After similar to the more common gallbladder malignancies, Case Reports in Oncological Medicine 3 (a) (b) (c) (d) (e) (f) (g) (h) Figure 2: Representative H&E sections of the gallbladder LCNEC and some of the immunostains performed. Very low-power H&E view (20x) of the LCNEC showing necrosis and tumor cells (a), low-power H&E section (40x) showing the trabecular growth pattern (b), and a middle-power view (200x) showing the neuroendocrine features of the LCNEC (c). Sections (d–h) show the CD56, AE1/AE3, c-kit, neuron-specific enolase, and Ki-67 immunostains, respectively. 4 Case Reports in Oncological Medicine literature,” World Journal of Surgical Oncology, vol. 13, no. 1, including jaundice and abdominal pain/discomfort [5]. p. 114, 2015. Common radiological findings include a mass in place of the gallbladder, focal or diffuse gallbladder wall thickening, [5] A. Tidjane, N. Boudjenan, A. Bengueddach et al., “Pure large cell neuroendocrine carcinoma of the gallbladder, is surgical and direct invasion of the tumor into the liver or metastasis relentlessness beneficial? A case report and literature review,” to the surrounding lymph nodes [1]. LCNECs are typically International Cancer Conference Journal, vol. 10, no. 2, very aggressive, with a median survival time of 15 months pp. 127–133, 2021. and with a range of 21 days to 69 months [5]. For qualifying [6] M. Murakami, K. Katayama, S. Kato et al., “Large-cell neuro- patients, optimal treatment for these tumors is complete sur- endocrine carcinoma of the common bile duct: a case report gical resection with surrounding lymph node clearance and and a review of literature,” Surgical Case Reports, vol. 2, hepatic lobectomy, with recurrences being very common no. 1, p. 141, 2016. [5]. In the event of an unresectable tumor, systemic chemo- [7] S. B. Park, S. B. Moon, Y. J. Ryu et al., “Primary large cell neu- therapy is the next treatment option, which employs the roendocrine carcinoma in the common bile duct: first Asian same platinum-based chemotherapy regimen, often with case report,” World Journal of Gastroenterology, vol. 20, radiation therapy, as is used for small cell neuroendocrine no. 47, pp. 18048–18052, 2014. carcinoma treatment [5, 8]. The efficacy of traditional che- [8] A. Iyoda, T. Makino, S. Koezuka, H. Otsuka, and Y. Hata, motherapy with additional radiotherapy remains unclear “Treatment options for patients with large cell neuroendocrine due to insensitivity of general neuroendocrine tumors to carcinoma of the lung,” General Thoracic and Cardiovascular radiotherapy; however, this is a treatment option for Surgery, vol. 62, no. 6, pp. 351–356, 2014. patients with multiple metastases or an unresectable tumor [9] I. M. Modlin, M. Kidd, I. Drozdov, Z. L. Siddique, and B. I. [9]. Recently, immunotherapy with ipilimumab and nivo- Gustafsson, “Pharmacotherapy of neuroendocrine cancers,” lumab has shown some promise in a small phase II clini- Expert Opinion Pharmacotherapy, vol. 9, no. 15, pp. 2617– cal trial treating LCNECs [10]. Due to the rarity of these 2626, 2008. tumors, especially of pure LCNECs of the gallbladder, [10] S. Patel, “A phase II basket trial of nivolumab and ipilimumab there is much that is unknown about how these extremely in rare tumors (NET cohort),” American Association of Cancer rare tumors should be treated [8, 10]. An accurate diagno- Research, vol. 79, 2019. sis of LCNEC is also essential as the treatment for these [11] S. Buscemi, E. Orlando, G. Damiano et al., ““Pure” large cell tumors is different than that used for the more common neuroendocrine carcinoma of the gallbladder. Report of a case adenocarcinomas of the gallbladder [5, 8, 11]. In conclu- and review of the literature,” International Journal of Surgery, sion, histologically pure LCNEC tumors of the gallbladder vol. 28, Supplement 1, pp. S128–S132, 2016. are exceedingly rare [5, 11]. The unique nature of this tumor requires that further studies be utilized to optimize its treatment. In particular, immune and DNA sequence analyses, multimodal treatment regimes, and immune therapies will likely play an important role in the future treatment of these rare malignancies [5, 11]. Conflicts of Interest The authors declare that there is no conflict of interest regarding the publication of this article. References [1] K. M. Eltawil, B. I. Gustafsson, M. Kidd, and I. M. Modlin, “Neuroendocrine tumors of the gallbladder,” Journal of Clini- cal Gastroenterology, vol. 44, no. 10, pp. 687–695, 2010. [2] M. Papotti, P. Cassoni, A. Sapino, G. Passarino, J. E. Krueger, and J. Albores-Saavedra, “Large cell neuroendocrine carci- noma of the gallbladder: report of two cases,” The American Journal of Surgical Pathology, vol. 24, no. 10, pp. 1424–1428, [3] W. D. Travis, R. I. Linnoila, M. G. Tsokos et al., “Neuroendo- crine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohisto- chemical, and flow cytometric study of 35 cases,” The Ameri- can Journal of Surgical Pathology, vol. 15, no. 6, pp. 529–553, [4] W. Liu, L. Wang, X. D. He, C. Feng, X. Y. Chang, and Z. H. Lu, “Mixed large cell neuroendocrine carcinoma and adenocarci- noma of the gallbladder: a case report and brief review of the

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Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: May 21, 2022

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