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The Three P’s: Parotid, PD-L1, and Pembrolizumab

The Three P’s: Parotid, PD-L1, and Pembrolizumab Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 2305315, 3 pages https://doi.org/10.1155/2019/2305315 Case Report Amanda Wiggins , Zhaohui Arter, and Tamie Kerns Tripler Army Medical Center, 1 Jarrett White Road, DHCK-DM, Honolulu, HI 96859, USA Correspondence should be addressed to Amanda Wiggins; amanda.keith8@gmail.com Received 31 December 2018; Accepted 28 May 2019; Published 11 June 2019 Academic Editor: Francesco A. Mauri Copyright © 2019 Amanda Wiggins 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. We present a case of recurrent, platinum-refractory undifferentiated carcinoma of the parotid which was treated with checkpoint inhibitor, Pembrolizumab, and achieved a complete response to therapy. We review the literature of checkpoint inhibitor use in undifferentiated carcinoma of the parotid. 1. Introduction 2 5×2 8cm and 2 7×2 8cm, respectively, multiple ipsilat- eral lymph nodes measuring up to 1.9 cm in diameter, and Immunologic therapy is an emerging treatment modality in an asymmetrically enhancing left nasopharynx. A fine needle oncology, which may provide prolonged survival in numer- aspiration (FNA) of an involved local lymph node revealed a ous malignancies [1]. PD-L1 expression has been found to nonkeratinizing, undifferentiated carcinoma composed of have both prognostic and treatment utility in the manage- pleomorphic cells positive for Epstein-Barr virus (EBV). ment of metastatic malignancies [2]. We present a patient The differential diagnosis based on FNA findings includes with one hundred percent PD-L1 expression in an undif- primary parotid carcinoma, lymphoepithelial carcinoma, or ferentiated, EBV positive, metastatic carcinoma of parotid metastatic nasopharyngeal carcinoma. Blind biopsies of the origin with near complete remission after treatment with nasopharynx were negative. PET/CT revealed hypermeta- Pembrolizumab. bolic activity in the left parotid gland and several local nodes, highly suggestive of a primary parotid neoplasm. Excisional biopsy revealed a nonkeratinizing, undifferentiated carci- 2. Case Presentation noma composed of pleomorphic cells, positive for Epstein- A previously healthy 52-year-old Samoan woman initially Barr virus (EBV). The results of subsequent excisional biopsy of the parotid gland masses were consistent with previous presented to her primary care provider with complaints of otalgia and swelling in the left side of her face for three weeks. FNA findings. She reported no facial weakness, trismus, dysphagia, odyno- The patient was staged as Stage IVa (cT3N2bM0) per phagia, dental pain, fevers, chills, weight loss, and fatigue. AJCC 7th ed. Due to the extension of the parotid disease On initial physical exam, a 6 cm nontender, subcutaneous, toward the main trunk of cranial nerve (CN) VII, there was cystic mass was palpated in the left parotid. The oral cavity a concern for postoperative CN VII palsy with surgical man- showed no deformities or evidence of abnormalities. There agement. Surgery was therefore deferred, and definitive was no lymphadenopathy of the anterior or posterior cervical cisplatin-based concurrent/chemoradiation treatment was chain, supraclavicular, or axillary lymph nodes. At that time, initiated. On first surveillance PET/CT, at 12 weeks postcon- she was prescribed with antibiotics for presumed sialadenitis current chemoradiation treatment, she was found to have with no effect on her symptoms. On the next follow-up visit, PET-avid hepatic and bone lesions (Figure 1). A CT-guided she was referred to otolaryngology for further evaluation. portacaval lymph node biopsy confirmed a metastatic disease A neck and chest computer topography (CT) scan (Figure 2). IHC staining of the portal cava lymph node demonstrated two necrotic left parotid masses measuring demonstrated 100% PD-L1 expression. Next Generation 2 Case Reports in Oncological Medicine 10.00 10.00 2 2 5 5 0 0 0.00 0.00 50 % PET 50 % PET 1200/120 3.3 3.3 Figure 1: PET/CT image prior to immunotherapy. Figure 3: PET/CT after 4 cycles of Pembrolizumab. relationship between NPC, salivary carcinomas, and other EBV-associated malignancies. First, ninety-five percent of primary nasopharyngeal carcinomas are poorly differentiated or undifferentiated, nonkeratinizing carcinomas, with the highest incidence in the Asian and Pacific islands [9]. NPC is also well known to be an EBV-associated malignancy and characteristically causes lymphocytic infiltrates surrounding tumors [9]. Finally, the upregulation of PD-L1 expression has been documented in multiple EBV-associated malignan- cies. While the exact mechanism of PD-L1 upregulation is not well understood, it is suspected to be due to constitutively activated oncogenic pathways [9–11]. In one study, all patients with high tumor PD-L1 expression (PD-L1 expressed Figure 2: Biopsy of metastatic lesion involving the portacaval in 90-100% of malignant cells) were positive for EBV, similar lymph node. to our patient [11]. There is conflicting data on the prognostic value of PD-L1 expression in NPC; however, recent studies Sequencing was negative for additional mutations. Pembroli- seem to suggest that a high percentage of PD-L1 expression zumab monotherapy resulted in a near complete resolution may be associated with a poor prognosis [12]. Likewise, in of her hepatic metastasis and complete metabolic resolution other salivary gland malignancies, higher PD-L1 expression of the left parotid mass, cervical adenopathy, and skeletal has been associated with a more aggressive cancer [13]. lesions on PET/CT following four cycles (Figure 3). Follow- In this patient, the similarities between her histology and up PET/CT scan found a progression of disease per RECIST disease progression bears a striking resemblance to that seen v1.1 criteria after seven months of treatment. in NPC, suggesting a similar pathophysiology of malignant transformation in undifferentiated primary parotid carci- noma and aggressive behavior. 3. Discussion Targeted immunologic chemotherapy is emerging as a Salivary gland malignancies are uncommon, accounting for treatment for metastatic malignancies. Research regarding 3-6.5% of all head and neck cancers [3]. Undifferentiated sal- the use of PD-L1 inhibitors in multiple malignancies such as metastatic renal cell carcinoma, lymphoma, breast, colo- ivary gland malignancies, however, are exceedingly rare. Less than 1% of all salivary gland tumors are lymphoepithelial or rectal cancer, nonsmall cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell, and melanoma is undifferentiated carcinoma, carrying a poor prognosis [4]. The reported incidence of undifferentiated carcinoma ranged currently ongoing [10, 14–17]. These studies continue to elu- from 1 to 5.5% in all parotid gland malignancies [5]. A liter- cidate the place of Pembrolizumab in various malignancies. For the treatment of recurrent or metastatic head and neck ature search for undifferentiated parotid carcinoma returned seldom results; most of these reports were small case series squamous cell cancers, Pembrolizumab was only recently [6–8]. Furthermore, this patient with poorly differentiated approved in 2016 by the Food and Drug Administration parotid carcinoma behaved more like a nasopharyngeal car- [2]. Published last year, the KEYNOTE-028 was a multico- cinoma (NPC). Traditionally, salivary gland malignancies hort, nonrandomized, phase Ib study of advanced salivary gland tumors with PD-L1 expression undergoing treatment are slow growing and become metastatic late in the disease process [1]. Conversely, our patient developed metastatic dis- with Pembrolizumab [1]. In this study, 46% of patients expe- ease early in her course following cytotoxic chemotherapy rienced stable disease with similar adverse events as reported and local radiation. in prior studies. Many features of our patient’s case mirror previously Additional trials investigating immunotherapy in recur- rent and refractory head and neck cancer are now recruiting, reported characteristics of NPC, which may suggest a Case Reports in Oncological Medicine 3 carcinoma of the parotid gland,” Auris Nasus Larynx, vol. 30, for example, a phase-IIb study by Hsu et al. assessing benefit no. 3, pp. 273–277, 2003. of using PD-L1 inhibitors for treatment of recurrent or metastatic NPC, which was published after the initiation of [6] K. K. Hui, M. A. Luna, J. G. Batsakis, N. G. Ordóñez, and R. Weber, “Undifferentiated carcinomas of the major salivary this patient’s treatment [18]. In the 27 patients treated with glands,” Oral Surgery, Oral Medicine, Oral Pathology, vol. 69, Pembrolizumab, there was a promising outcome with an no. 1, pp. 76–83, 1990. objective response rate of 25% per the RESIST v1.1 [18]; [7] C. J. R. Stewart, K. MacKenzie, G. W. McGarry, and A. Mowat, however, they could only confidently say that Pembrolizu- “Fine-needle aspiration cytology of salivary gland: a review mab would be safe in this population given low power. It of 341 cases,” Diagnostic Cytopathology, vol. 22, no. 3, is important to note the growing use of targeted therapy pp. 139–146, 2000. has largely been oncologist driven with patients who have [8] J. G. Moore and T. Bocklage, “Fine-needle aspiration biopsy of poor prognosis and limited therapeutic options, as seen in large-cell undifferentiated carcinoma of the salivary glands: this case. presentation of two cases, literature review, and differential As immunotherapies continue to improve and provide cytodiagnosis of high-grade salivary gland malignancies,” significantly longer progression free and overall survival Diagnostic Cytopathology, vol. 19, no. 1, pp. 44–50, 1998. benefit, genetic sequencing and IHC staining should be [9] W. Fang, J. Zhang, S. Hong et al., “EBV-driven LMP1 and incorporated into the work-up of a recurrent or metastatic IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: head and neck malignancies. implications for oncotargeted therapy,” Oncotarget, vol. 5, Still, additional research is needed to fully understand the no. 23, pp. 12189–12202, 2014. role of immunotherapies in rare disease types. [10] B. J. Chen, B. Chapuy, J. Ouyang et al., “PD-L1 expression is characteristic of a subset of aggressive B- cell lymphomas Consent and virus-associated malignancies,” Clinical Cancer Research, vol. 19, no. 13, pp. 3462–3473, 2013. Consent was verbally obtained from the next of kin. [11] A. M. V. Chang, S. I. Chiosea, A. Altman, H. A. Pagdanganan, and C. Ma, “Programmed death-ligand 1 expression, microsat- Disclosure ellite instability, Epstein-Barr virus, and human papillomavi- rus in nasopharyngeal carcinomas of patients from the The views expressed in this abstract/manuscript are those of Philippines,” Head and Neck Pathology, vol. 11, no. 2, the authors and do not reflect the official policy or position of pp. 203–211, 2017. the Department of the Army, Department of Defense, or the [12] Y. F. Li, J. W. Ding, L. M. Liao et al., “Expression of US Government. programmed death ligand-1 predicts poor outcome in naso- pharyngeal carcinoma,” Molecular and Clinical Oncology, vol. 7, no. 3, pp. 378–382, 2017. Conflicts of Interest [13] T. Mukaigawa, R. Hayashi, K. Hashimoto, T. Ugumori, The authors declare that they have no conflicts of interests. N. Hato, and S. Fujii, “Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas,” Journal of Surgical Oncology, vol. 114, no. 1, Acknowledgments pp. 36–43, 2016. Peer reviewed internally by Dr. Berenberg, Dr. Murphy, and [14] J. W. T. Toh, P. de Souza, S. H. Lim et al., “The potential value Dr. Guess. Images were provided by Dr. Kao, MD Tripler of immunotherapy in colorectal cancers: review of the evi- radiology. dence for programmed death-1 inhibitor therapy,” Clinical Colorectal Cancer, vol. 15, no. 4, pp. 285–291, 2016. [15] M. Reck, D. Rodríguez-Abreu, A. G. Robinson et al., “Pembro- References lizumab versus chemotherapy for PD-L1-positive non- small- cell lung cancer,” The New England Journal of Medicine, [1] R. B. Cohen, J. P. Delord, T. Doi et al., “Pembrolizumab for the treatment of advanced salivary gland carcinoma: findings of vol. 375, no. 19, pp. 1823–1833, 2016. the phase 1b KEYNOTE-028 study,” American Journal of [16] A. Ribas, I. Puzanov, R. Dummer et al., “Pembrolizumab Clinical Oncology, vol. 41, no. 11, pp. 1083–1088, 2018. versus investigator-choice chemotherapy for ipilimumab- [2] E. Larkins, G. M. Blumenthal, W. Yuan et al., “FDA approval refractory melanoma (KEYNOTE-002): a randomised, con- summary: pembrolizumab for the treatment of recurrent or trolled, phase 2 trial,” The Lancet Oncology, vol. 16, no. 8, metastatic head and neck squamous cell carcinoma with pp. 908–918, 2015. disease progression on or after platinum-containing chemo- [17] E. Roper, T. Lum, C. E. Palme et al., “PD-L1 expression therapy,” Oncologist, vol. 22, no. 7, pp. 873–878, 2017. predicts longer disease free survival in high risk head and neck [3] K. Harada, T. Ferdous, and Y. Ueyama, “PD-L1 expression in cutaneous squamous cell carcinoma,” Pathology, vol. 49, no. 5, malignant salivary gland tumors,” BMC Cancer, vol. 18, no. 1, pp. 499–505, 2017. p. 156, 2018. [18] C. Hsu, S. H. Lee, S. Ejadi et al., “Safety and antitumor [4] V. Kumar, A. K. Abbas, and J. C. Aster, Robbins and Cotran activity of pembrolizumab in patients with programmed Pathologic Basis of Disease, Elsevier/Saunders, Philadelphia, death-ligand 1–positive nasopharyngeal carcinoma: results PA, USA, 9th edition, 2015. of the KEYNOTE-028 study,” Journal of Clinical Oncology, [5] C. Hatta, T. Terada, J. Okita, M. Kakibuchi, A. Kubota, and vol. 35, no. 36, pp. 4050–4056, 2017. M. Sakagami, “Clinicopathological study of undifferentiated MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

The Three P’s: Parotid, PD-L1, and Pembrolizumab

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Copyright © 2019 Amanda Wiggins 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 2019, Article ID 2305315, 3 pages https://doi.org/10.1155/2019/2305315 Case Report Amanda Wiggins , Zhaohui Arter, and Tamie Kerns Tripler Army Medical Center, 1 Jarrett White Road, DHCK-DM, Honolulu, HI 96859, USA Correspondence should be addressed to Amanda Wiggins; amanda.keith8@gmail.com Received 31 December 2018; Accepted 28 May 2019; Published 11 June 2019 Academic Editor: Francesco A. Mauri Copyright © 2019 Amanda Wiggins 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. We present a case of recurrent, platinum-refractory undifferentiated carcinoma of the parotid which was treated with checkpoint inhibitor, Pembrolizumab, and achieved a complete response to therapy. We review the literature of checkpoint inhibitor use in undifferentiated carcinoma of the parotid. 1. Introduction 2 5×2 8cm and 2 7×2 8cm, respectively, multiple ipsilat- eral lymph nodes measuring up to 1.9 cm in diameter, and Immunologic therapy is an emerging treatment modality in an asymmetrically enhancing left nasopharynx. A fine needle oncology, which may provide prolonged survival in numer- aspiration (FNA) of an involved local lymph node revealed a ous malignancies [1]. PD-L1 expression has been found to nonkeratinizing, undifferentiated carcinoma composed of have both prognostic and treatment utility in the manage- pleomorphic cells positive for Epstein-Barr virus (EBV). ment of metastatic malignancies [2]. We present a patient The differential diagnosis based on FNA findings includes with one hundred percent PD-L1 expression in an undif- primary parotid carcinoma, lymphoepithelial carcinoma, or ferentiated, EBV positive, metastatic carcinoma of parotid metastatic nasopharyngeal carcinoma. Blind biopsies of the origin with near complete remission after treatment with nasopharynx were negative. PET/CT revealed hypermeta- Pembrolizumab. bolic activity in the left parotid gland and several local nodes, highly suggestive of a primary parotid neoplasm. Excisional biopsy revealed a nonkeratinizing, undifferentiated carci- 2. Case Presentation noma composed of pleomorphic cells, positive for Epstein- A previously healthy 52-year-old Samoan woman initially Barr virus (EBV). The results of subsequent excisional biopsy of the parotid gland masses were consistent with previous presented to her primary care provider with complaints of otalgia and swelling in the left side of her face for three weeks. FNA findings. She reported no facial weakness, trismus, dysphagia, odyno- The patient was staged as Stage IVa (cT3N2bM0) per phagia, dental pain, fevers, chills, weight loss, and fatigue. AJCC 7th ed. Due to the extension of the parotid disease On initial physical exam, a 6 cm nontender, subcutaneous, toward the main trunk of cranial nerve (CN) VII, there was cystic mass was palpated in the left parotid. The oral cavity a concern for postoperative CN VII palsy with surgical man- showed no deformities or evidence of abnormalities. There agement. Surgery was therefore deferred, and definitive was no lymphadenopathy of the anterior or posterior cervical cisplatin-based concurrent/chemoradiation treatment was chain, supraclavicular, or axillary lymph nodes. At that time, initiated. On first surveillance PET/CT, at 12 weeks postcon- she was prescribed with antibiotics for presumed sialadenitis current chemoradiation treatment, she was found to have with no effect on her symptoms. On the next follow-up visit, PET-avid hepatic and bone lesions (Figure 1). A CT-guided she was referred to otolaryngology for further evaluation. portacaval lymph node biopsy confirmed a metastatic disease A neck and chest computer topography (CT) scan (Figure 2). IHC staining of the portal cava lymph node demonstrated two necrotic left parotid masses measuring demonstrated 100% PD-L1 expression. Next Generation 2 Case Reports in Oncological Medicine 10.00 10.00 2 2 5 5 0 0 0.00 0.00 50 % PET 50 % PET 1200/120 3.3 3.3 Figure 1: PET/CT image prior to immunotherapy. Figure 3: PET/CT after 4 cycles of Pembrolizumab. relationship between NPC, salivary carcinomas, and other EBV-associated malignancies. First, ninety-five percent of primary nasopharyngeal carcinomas are poorly differentiated or undifferentiated, nonkeratinizing carcinomas, with the highest incidence in the Asian and Pacific islands [9]. NPC is also well known to be an EBV-associated malignancy and characteristically causes lymphocytic infiltrates surrounding tumors [9]. Finally, the upregulation of PD-L1 expression has been documented in multiple EBV-associated malignan- cies. While the exact mechanism of PD-L1 upregulation is not well understood, it is suspected to be due to constitutively activated oncogenic pathways [9–11]. In one study, all patients with high tumor PD-L1 expression (PD-L1 expressed Figure 2: Biopsy of metastatic lesion involving the portacaval in 90-100% of malignant cells) were positive for EBV, similar lymph node. to our patient [11]. There is conflicting data on the prognostic value of PD-L1 expression in NPC; however, recent studies Sequencing was negative for additional mutations. Pembroli- seem to suggest that a high percentage of PD-L1 expression zumab monotherapy resulted in a near complete resolution may be associated with a poor prognosis [12]. Likewise, in of her hepatic metastasis and complete metabolic resolution other salivary gland malignancies, higher PD-L1 expression of the left parotid mass, cervical adenopathy, and skeletal has been associated with a more aggressive cancer [13]. lesions on PET/CT following four cycles (Figure 3). Follow- In this patient, the similarities between her histology and up PET/CT scan found a progression of disease per RECIST disease progression bears a striking resemblance to that seen v1.1 criteria after seven months of treatment. in NPC, suggesting a similar pathophysiology of malignant transformation in undifferentiated primary parotid carci- noma and aggressive behavior. 3. Discussion Targeted immunologic chemotherapy is emerging as a Salivary gland malignancies are uncommon, accounting for treatment for metastatic malignancies. Research regarding 3-6.5% of all head and neck cancers [3]. Undifferentiated sal- the use of PD-L1 inhibitors in multiple malignancies such as metastatic renal cell carcinoma, lymphoma, breast, colo- ivary gland malignancies, however, are exceedingly rare. Less than 1% of all salivary gland tumors are lymphoepithelial or rectal cancer, nonsmall cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell, and melanoma is undifferentiated carcinoma, carrying a poor prognosis [4]. The reported incidence of undifferentiated carcinoma ranged currently ongoing [10, 14–17]. These studies continue to elu- from 1 to 5.5% in all parotid gland malignancies [5]. A liter- cidate the place of Pembrolizumab in various malignancies. For the treatment of recurrent or metastatic head and neck ature search for undifferentiated parotid carcinoma returned seldom results; most of these reports were small case series squamous cell cancers, Pembrolizumab was only recently [6–8]. Furthermore, this patient with poorly differentiated approved in 2016 by the Food and Drug Administration parotid carcinoma behaved more like a nasopharyngeal car- [2]. Published last year, the KEYNOTE-028 was a multico- cinoma (NPC). Traditionally, salivary gland malignancies hort, nonrandomized, phase Ib study of advanced salivary gland tumors with PD-L1 expression undergoing treatment are slow growing and become metastatic late in the disease process [1]. Conversely, our patient developed metastatic dis- with Pembrolizumab [1]. In this study, 46% of patients expe- ease early in her course following cytotoxic chemotherapy rienced stable disease with similar adverse events as reported and local radiation. in prior studies. Many features of our patient’s case mirror previously Additional trials investigating immunotherapy in recur- rent and refractory head and neck cancer are now recruiting, reported characteristics of NPC, which may suggest a Case Reports in Oncological Medicine 3 carcinoma of the parotid gland,” Auris Nasus Larynx, vol. 30, for example, a phase-IIb study by Hsu et al. assessing benefit no. 3, pp. 273–277, 2003. of using PD-L1 inhibitors for treatment of recurrent or metastatic NPC, which was published after the initiation of [6] K. K. Hui, M. A. Luna, J. G. Batsakis, N. G. Ordóñez, and R. Weber, “Undifferentiated carcinomas of the major salivary this patient’s treatment [18]. In the 27 patients treated with glands,” Oral Surgery, Oral Medicine, Oral Pathology, vol. 69, Pembrolizumab, there was a promising outcome with an no. 1, pp. 76–83, 1990. objective response rate of 25% per the RESIST v1.1 [18]; [7] C. J. R. Stewart, K. MacKenzie, G. W. McGarry, and A. Mowat, however, they could only confidently say that Pembrolizu- “Fine-needle aspiration cytology of salivary gland: a review mab would be safe in this population given low power. It of 341 cases,” Diagnostic Cytopathology, vol. 22, no. 3, is important to note the growing use of targeted therapy pp. 139–146, 2000. has largely been oncologist driven with patients who have [8] J. G. Moore and T. Bocklage, “Fine-needle aspiration biopsy of poor prognosis and limited therapeutic options, as seen in large-cell undifferentiated carcinoma of the salivary glands: this case. presentation of two cases, literature review, and differential As immunotherapies continue to improve and provide cytodiagnosis of high-grade salivary gland malignancies,” significantly longer progression free and overall survival Diagnostic Cytopathology, vol. 19, no. 1, pp. 44–50, 1998. benefit, genetic sequencing and IHC staining should be [9] W. Fang, J. Zhang, S. Hong et al., “EBV-driven LMP1 and incorporated into the work-up of a recurrent or metastatic IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: head and neck malignancies. implications for oncotargeted therapy,” Oncotarget, vol. 5, Still, additional research is needed to fully understand the no. 23, pp. 12189–12202, 2014. role of immunotherapies in rare disease types. [10] B. J. Chen, B. Chapuy, J. Ouyang et al., “PD-L1 expression is characteristic of a subset of aggressive B- cell lymphomas Consent and virus-associated malignancies,” Clinical Cancer Research, vol. 19, no. 13, pp. 3462–3473, 2013. Consent was verbally obtained from the next of kin. [11] A. M. V. Chang, S. I. Chiosea, A. Altman, H. A. Pagdanganan, and C. Ma, “Programmed death-ligand 1 expression, microsat- Disclosure ellite instability, Epstein-Barr virus, and human papillomavi- rus in nasopharyngeal carcinomas of patients from the The views expressed in this abstract/manuscript are those of Philippines,” Head and Neck Pathology, vol. 11, no. 2, the authors and do not reflect the official policy or position of pp. 203–211, 2017. the Department of the Army, Department of Defense, or the [12] Y. F. Li, J. W. Ding, L. M. Liao et al., “Expression of US Government. programmed death ligand-1 predicts poor outcome in naso- pharyngeal carcinoma,” Molecular and Clinical Oncology, vol. 7, no. 3, pp. 378–382, 2017. Conflicts of Interest [13] T. Mukaigawa, R. Hayashi, K. Hashimoto, T. Ugumori, The authors declare that they have no conflicts of interests. N. Hato, and S. Fujii, “Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas,” Journal of Surgical Oncology, vol. 114, no. 1, Acknowledgments pp. 36–43, 2016. Peer reviewed internally by Dr. Berenberg, Dr. Murphy, and [14] J. W. T. Toh, P. de Souza, S. H. Lim et al., “The potential value Dr. Guess. Images were provided by Dr. Kao, MD Tripler of immunotherapy in colorectal cancers: review of the evi- radiology. dence for programmed death-1 inhibitor therapy,” Clinical Colorectal Cancer, vol. 15, no. 4, pp. 285–291, 2016. [15] M. Reck, D. Rodríguez-Abreu, A. G. Robinson et al., “Pembro- References lizumab versus chemotherapy for PD-L1-positive non- small- cell lung cancer,” The New England Journal of Medicine, [1] R. B. Cohen, J. P. Delord, T. Doi et al., “Pembrolizumab for the treatment of advanced salivary gland carcinoma: findings of vol. 375, no. 19, pp. 1823–1833, 2016. the phase 1b KEYNOTE-028 study,” American Journal of [16] A. Ribas, I. Puzanov, R. Dummer et al., “Pembrolizumab Clinical Oncology, vol. 41, no. 11, pp. 1083–1088, 2018. versus investigator-choice chemotherapy for ipilimumab- [2] E. Larkins, G. M. Blumenthal, W. Yuan et al., “FDA approval refractory melanoma (KEYNOTE-002): a randomised, con- summary: pembrolizumab for the treatment of recurrent or trolled, phase 2 trial,” The Lancet Oncology, vol. 16, no. 8, metastatic head and neck squamous cell carcinoma with pp. 908–918, 2015. disease progression on or after platinum-containing chemo- [17] E. Roper, T. Lum, C. E. Palme et al., “PD-L1 expression therapy,” Oncologist, vol. 22, no. 7, pp. 873–878, 2017. predicts longer disease free survival in high risk head and neck [3] K. Harada, T. Ferdous, and Y. Ueyama, “PD-L1 expression in cutaneous squamous cell carcinoma,” Pathology, vol. 49, no. 5, malignant salivary gland tumors,” BMC Cancer, vol. 18, no. 1, pp. 499–505, 2017. p. 156, 2018. [18] C. Hsu, S. H. Lee, S. Ejadi et al., “Safety and antitumor [4] V. Kumar, A. K. Abbas, and J. C. Aster, Robbins and Cotran activity of pembrolizumab in patients with programmed Pathologic Basis of Disease, Elsevier/Saunders, Philadelphia, death-ligand 1–positive nasopharyngeal carcinoma: results PA, USA, 9th edition, 2015. of the KEYNOTE-028 study,” Journal of Clinical Oncology, [5] C. Hatta, T. Terada, J. Okita, M. Kakibuchi, A. Kubota, and vol. 35, no. 36, pp. 4050–4056, 2017. M. Sakagami, “Clinicopathological study of undifferentiated MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Journal

Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: Jun 11, 2019

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