- Email: [email protected]
Clear cell sarcoma of the nasal soft tissue envelope
Otolaryngology Case Reports 13 (2019) 100127
Contents lists available at ScienceDirect
Otolaryngology Case Reports journal homepage: www.elsevier.com/locate/xocr
Clear cell sarcoma of the nasal soft tissue envelope a
a
a
T b
c
Dustin A. Silverman , Scott W. Smith , Garth F. Essig Jr. , Stephen Y. Kang , Lynn Schoenfield , Leslie R. Kima,∗ Department of Otolaryngology – Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA Department of Otolaryngology – Head and Neck Surgery, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH, USA c Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA a
b
A R T I C LE I N FO
A B S T R A C T
Originally presented for oral presentation at the 12th International Symposium of Facial Plastic Surgery, October 15, 2018; Dallas, TX
Objective(s): Clear cell sarcoma (CCS) is a rare clinical entity with limited head and neck reports. This is the first known case of primary CCS of the nasal soft tissue envelope. The primary objective is to understand the clinical and histopathologic features of CCS of the head and neck. Secondary measures are to recognize the wide differential diagnosis of nasal soft tissue masses and identify treatment strategies to achieve complete resection of nasal soft tissue tumors while optimizing functional and aesthetic results. Methods: Case report. Results: A 38-year-old otherwise healthy Caucasian male presented with a 2 cm subcutaneous mass of the nasal soft tissue envelope. Confined to the lateral nasal wall, the painless mass gradually increased in size over two years and contributed to nasal obstruction. The patient underwent complete resection via an open septorhinoplasty approach with concomitant functional nasal airway surgery. Pathology, immunohistochemistry, and cytogenetics were consistent with CCS (melanoma of soft parts). As no definitive or established adjuvant medical therapy exists, further treatment was suspended in favor of serial imaging. The patient remains clinically free of disease 24 months following diagnosis with subjective improvement in nasal airflow and cosmesis. Conclusion: The differential diagnosis of soft tissue nasal masses is varied. Surgeons should maintain a high index of suspicion for more insidious pathology in otherwise benign-appearing nasal soft tissue masses. An open rhinoplasty approach may be prudent for larger lesions to achieve complete resection with restoration of form and function.
Keywords: Clear cell sarcoma Melanoma of soft parts Facial plastics Reconstructive surgery Rhinoplasty Nasal reconstruction
Introduction Clear cell sarcoma (CCS)—previously referred to as melanoma of soft parts—is a rare and aggressive malignant tumor that primarily arises from the deeper aponeurotic tissue and tendons of the extremities, predominantly involving the foot and ankle of younger adults. CCS portends an overall poor prognosis and is associated with local recurrence and distant metastases despite wide resection and tumor-free margins. While numerous descriptions of this tumor have been reported as it relates to musculoskeletal involvement, there is a paucity of literature focusing on the presentation and treatment of these tumors in the head and neck region. Given the relative rarity of CCS and even smaller subset presenting in the head and neck, the majority of these cases are outlined as isolated case reports or contained within larger reviews of the literature [1,2].
To the authors’ knowledge, this is the first reported case of primary CCS involving the nasal soft tissue envelope. This poses an even more challenging diagnostic dilemma for clinicians as the differential diagnosis of soft tissue nasal masses is highly varied. Cutaneous neoplasms aside, there is limited information regarding the incidence of malignant nasal soft tissue masses and even fewer treatment algorithms on how to best approach the surgical management of these tumors, while optimizing functional, aesthetic and potential oncologic outcomes. As such, we describe the first known case of CCS presenting within the nasal soft tissue envelope, and suggest treatment strategies for achieving complete resection of similar tumors while optimizing outcomes. Case presentation A 38-year-old Caucasian male presented with a two-year history of a
∗ Corresponding author. Facial Plastic & Reconstructive Surgery, The Ohio State University Wexner Medical Center, 915 Olentangy River Rd., Columbus, OH, 43212, USA. E-mail address: [email protected] (L.R. Kim).
https://doi.org/10.1016/j.xocr.2019.100127 Received 21 June 2019; Accepted 22 August 2019 Available online 29 August 2019 2468-5488/ © 2019 Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Otolaryngology Case Reports 13 (2019) 100127
D.A. Silverman, et al.
Fig. 1. Left: preoperative presentation demonstrating a left-sided, firm, 2 cm mobile nasal mass within the subcutaneous tissue of the middle vault not fixed to overlying skin. Right: 6-month postoperative result.
Fig. 2. A) Preoperative axial computed tomography (CT) with contrast section with non-specific, homogenous and non-enhancing soft tissue thickening (arrow) B) Intraoperative image demonstrating an open rhinoplasty approach with an encapsulated, cystic mass within the left middle vault.
disease 24 months following diagnosis with subjective improvement in nasal airflow and excellent satisfaction with the final aesthetic result (Fig. 1).
gradually increasing left nasal sidewall mass associated with mild discomfort and nasal obstruction. Prior to presentation, fine needle aspiration biopsy was attempted but was non-diagnostic and complicated by several days of bleeding. Examination demonstrated a well-circumscribed, mobile, 2 cm soft tissue mass of the left nasal sidewall and soft tissue envelope (Fig. 1). In-office nasal endoscopy revealed a patent nasal cavity without tumor infiltration. Preoperative computed tomography (CT) of the face revealed non-specific, homogenous, and nonenhancing soft tissue thickening measuring 2.0 × 1.2 cm with cephalad extent (Fig. 2A). The patient underwent complete resection of an encapsulated, cystic mass via an open septorhinoplasty approach with concomitant functional nasal airway surgery including septoplasty, internal nasal valve repair with bilateral spreader grafts and inferior turbinate reduction (Fig. 2B). Notably, the overlying soft tissue envelope and underlying mucosa were left intact; no iatrogenic or external nasal defect was created. The patient underwent a postoperative positron emission tomography-computed tomography (PET/CT), which was negative for metastases. He completed four cycles of adjuvant ipilimumab; however, further FoundationOne® genomic testing revealed the presence of an EWSR1-ATF1 translocation without a BRAF mutation and, as such, the diagnosis was amended to CCS. As no definitive or established adjuvant medical therapy exists, further treatment was suspended in favor of serial surveillance imaging. The patient remains clinically free of
Discussion CCS shares many pathologic and immunohistochemical similarities to melanoma including the presence of melanin, a propensity for nodal metastases, and positive staining for S-100 and HMB-45 [3]. Unlike malignant melanoma, CCS lacks the classic BRAF mutation and is characterized by a unique genetic translocation, t(12; 22), which results in the formation of a highly-specific EWSR1-ATF1 fusion gene [4]. Overall, CCS portends a poor prognosis. In most cases, CCS follows an aggressive clinical course and may quickly progress with late metastases being common even after several years of being disease-free, with the latest recurrence documented at 29 years.3 Studies have correlated a poor prognosis with the most important variable being tumor size ≥5 cm in addition to local recurrence and the presence of distant metastasis [5]. To date, limited reports of head and neck CCS have been described. A 2013 review by Inoue et al. found that only 4 of 696 (0.6%) CCS cases occurred within the head and neck [2]. Feasel and colleagues presented a small case series of 3 patients with a review of the literature and identified a total of 10 primary cases of head and neck CCS with sub2
Otolaryngology Case Reports 13 (2019) 100127
D.A. Silverman, et al.
resection and frequent surveillance are crucial in order to detect the presence of late and distant metastases.
sites including the mandible, tongue, scalp, face, cheek, and lip [1]. Similarly, unusual cases of metastases to the nasal soft tissue envelope have been reported including clear cell renal cell carcinoma, papillary thyroid carcinoma, and testicular natural killer T-cell lymphoma (NKTCL) [6–8]. To the authors’ knowledge, our case is the first known report of primary clear cell sarcoma arising within the nasal soft tissue envelope. Despite the largely asymptomatic presentation of the nasal mass in our patient, the final pathologic diagnosis highlights the need to maintain a high index of suspicion for more insidious pathology in similar cases involving otherwise benign features. Although the total number of benign cases is likely significantly underreported as cases like epidermoid cysts are not being documented, it is important to note that uncommon pathology may occur within the soft tissue envelope, whether benign or malignant. In similar cases, patients may present primarily to the otolaryngologist or facial plastic surgeon and may be referred by dermatologists requesting excision for largely aesthetic and possibly functional purposes. The current case highlights the importance of balancing these goals which may be complicated in similar instances where the chance for malignancy is not initially suspected but ultimately discovered. As such, a thorough discussion of the wide differential of these lesions and contingencies for addressing malignant potential is warranted as the cosmetic and functional results may be complicated by the need for complete surgical resection and adjuvant therapy for these patients. Obtaining a biopsy for preoperative diagnosis is paramount and, in the event of a nondiagnostic result, a second or confirmatory biopsy may be indicated; however, this was not attempted in our patient. Although observation with serial examination and/or imaging may be warranted or preferred by the patient, surgical excision of a nasal soft tissue mass is generally recommended for diagnostic and therapeutic benefit. Three main approaches are recommended and include direct excision, open rhinoplasty, and a closed/endonasal rhinoplasty approach. Patient anatomy dictates technique selection with more severe deformities or larger masses ≥1.0–1.5 cm well-suited for an external approach and enhances the ability of the surgeon to achieve an en-bloc tumor resection while optimizing exposure to aid in the correction of the resulting functional and aesthetic deficits. The closed or endonasal rhinoplasty approach may be indicated in select cases; however, this technique is less amenable in the setting of larger lesions as the ease of resection increases in complexity. Moreover, the endonasal approach may complicate the successful en-bloc removal of these masses and the subsequent reconstruction of these defects, especially in cases where the chance for malignancy persists. From an oncologic perspective, complete surgical resection with tumor-free margins is required for curative intent in cases of clearly defined malignancy. Therefore, if concerns for potential malignancy are present, an open rhinoplasty approach is likely the safer strategy. Limited studies have explored the role of adjuvant chemotherapy and radiation following resection of CCS; however, results have been varied without a definitive consensus [5,9]. Nonetheless, complete
Conclusion CCS is a rare but aggressive tumor with limited head and neck presentations. A high index of suspicion for the possibility of malignant pathology in otherwise benign-appearing masses should be maintained. An external rhinoplasty approach may be best suited in order to achieve not only complete, en-bloc resection but also to correct functional deficits and maximize aesthetic results. Disclosures Note: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest None. Sponsorships None. Funding sources None. References [1] Feasel PC, Cheah AL, Fritchie K, Winn B, Piliang M, Billings SD. Primary clear cell sarcoma of the head and neck: a case series with review of the literature. J Cutan Pathol 2016;43:838–46. [2] Inoue S, Chepeha DB, Lucas DR, Faisal S, Stewart RC, Mushtaq R, et al. Clear cell sarcoma of the jaw: a case report and review of the literature. Int J Pediatr Hematol Oncol 2013;35:402–5. [3] Chung EB, Enzinger FM. Malignant melanoma of soft parts. A reassessment of clear cell sarcoma. Am J Surg Pathol 1983;7:405–13. [4] Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM, Baelde JJ, Hogendoorn PC. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Canc 2001;84:535–8. [5] Ferrari A, Casanova M, Bisogno G, Mattke A, Meazza C, Gandola L, et al. Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 2002;94:3269–76. [6] Cui P, Cong X, Yin J, Liu M, Wang X, Yang L, et al. Metastases to the nose from clear cell renal cell carcinoma: a case report. Medicine 2019;98:e14012. [7] Khan OA, Roses DF, Peck V. Papillary thyroid carcinoma metastatic to skin may herald aggressive disease. Endocr Pract: Off J Am College Endocrinol Am Assoc Clin Endocrinol 2010;16:446–8. [8] Naboush A, Farhat F, Nasser SM, Kamar FG. Bifocal presentation of primary testicular extranasal NK/T-Cell lymphoma: a case report and review of the literature. Case Rep Oncol Med 2013;2013. 267389. [9] Malchau SS, Hayden J, Hornicek F, Mankin HJ. Clear cell sarcoma of soft tissues. J Surg Oncol 2007;95:519–22.
3
Contents lists available at ScienceDirect
Otolaryngology Case Reports journal homepage: www.elsevier.com/locate/xocr
Clear cell sarcoma of the nasal soft tissue envelope a
a
a
T b
c
Dustin A. Silverman , Scott W. Smith , Garth F. Essig Jr. , Stephen Y. Kang , Lynn Schoenfield , Leslie R. Kima,∗ Department of Otolaryngology – Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA Department of Otolaryngology – Head and Neck Surgery, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH, USA c Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA a
b
A R T I C LE I N FO
A B S T R A C T
Originally presented for oral presentation at the 12th International Symposium of Facial Plastic Surgery, October 15, 2018; Dallas, TX
Objective(s): Clear cell sarcoma (CCS) is a rare clinical entity with limited head and neck reports. This is the first known case of primary CCS of the nasal soft tissue envelope. The primary objective is to understand the clinical and histopathologic features of CCS of the head and neck. Secondary measures are to recognize the wide differential diagnosis of nasal soft tissue masses and identify treatment strategies to achieve complete resection of nasal soft tissue tumors while optimizing functional and aesthetic results. Methods: Case report. Results: A 38-year-old otherwise healthy Caucasian male presented with a 2 cm subcutaneous mass of the nasal soft tissue envelope. Confined to the lateral nasal wall, the painless mass gradually increased in size over two years and contributed to nasal obstruction. The patient underwent complete resection via an open septorhinoplasty approach with concomitant functional nasal airway surgery. Pathology, immunohistochemistry, and cytogenetics were consistent with CCS (melanoma of soft parts). As no definitive or established adjuvant medical therapy exists, further treatment was suspended in favor of serial imaging. The patient remains clinically free of disease 24 months following diagnosis with subjective improvement in nasal airflow and cosmesis. Conclusion: The differential diagnosis of soft tissue nasal masses is varied. Surgeons should maintain a high index of suspicion for more insidious pathology in otherwise benign-appearing nasal soft tissue masses. An open rhinoplasty approach may be prudent for larger lesions to achieve complete resection with restoration of form and function.
Keywords: Clear cell sarcoma Melanoma of soft parts Facial plastics Reconstructive surgery Rhinoplasty Nasal reconstruction
Introduction Clear cell sarcoma (CCS)—previously referred to as melanoma of soft parts—is a rare and aggressive malignant tumor that primarily arises from the deeper aponeurotic tissue and tendons of the extremities, predominantly involving the foot and ankle of younger adults. CCS portends an overall poor prognosis and is associated with local recurrence and distant metastases despite wide resection and tumor-free margins. While numerous descriptions of this tumor have been reported as it relates to musculoskeletal involvement, there is a paucity of literature focusing on the presentation and treatment of these tumors in the head and neck region. Given the relative rarity of CCS and even smaller subset presenting in the head and neck, the majority of these cases are outlined as isolated case reports or contained within larger reviews of the literature [1,2].
To the authors’ knowledge, this is the first reported case of primary CCS involving the nasal soft tissue envelope. This poses an even more challenging diagnostic dilemma for clinicians as the differential diagnosis of soft tissue nasal masses is highly varied. Cutaneous neoplasms aside, there is limited information regarding the incidence of malignant nasal soft tissue masses and even fewer treatment algorithms on how to best approach the surgical management of these tumors, while optimizing functional, aesthetic and potential oncologic outcomes. As such, we describe the first known case of CCS presenting within the nasal soft tissue envelope, and suggest treatment strategies for achieving complete resection of similar tumors while optimizing outcomes. Case presentation A 38-year-old Caucasian male presented with a two-year history of a
∗ Corresponding author. Facial Plastic & Reconstructive Surgery, The Ohio State University Wexner Medical Center, 915 Olentangy River Rd., Columbus, OH, 43212, USA. E-mail address: [email protected] (L.R. Kim).
https://doi.org/10.1016/j.xocr.2019.100127 Received 21 June 2019; Accepted 22 August 2019 Available online 29 August 2019 2468-5488/ © 2019 Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Otolaryngology Case Reports 13 (2019) 100127
D.A. Silverman, et al.
Fig. 1. Left: preoperative presentation demonstrating a left-sided, firm, 2 cm mobile nasal mass within the subcutaneous tissue of the middle vault not fixed to overlying skin. Right: 6-month postoperative result.
Fig. 2. A) Preoperative axial computed tomography (CT) with contrast section with non-specific, homogenous and non-enhancing soft tissue thickening (arrow) B) Intraoperative image demonstrating an open rhinoplasty approach with an encapsulated, cystic mass within the left middle vault.
disease 24 months following diagnosis with subjective improvement in nasal airflow and excellent satisfaction with the final aesthetic result (Fig. 1).
gradually increasing left nasal sidewall mass associated with mild discomfort and nasal obstruction. Prior to presentation, fine needle aspiration biopsy was attempted but was non-diagnostic and complicated by several days of bleeding. Examination demonstrated a well-circumscribed, mobile, 2 cm soft tissue mass of the left nasal sidewall and soft tissue envelope (Fig. 1). In-office nasal endoscopy revealed a patent nasal cavity without tumor infiltration. Preoperative computed tomography (CT) of the face revealed non-specific, homogenous, and nonenhancing soft tissue thickening measuring 2.0 × 1.2 cm with cephalad extent (Fig. 2A). The patient underwent complete resection of an encapsulated, cystic mass via an open septorhinoplasty approach with concomitant functional nasal airway surgery including septoplasty, internal nasal valve repair with bilateral spreader grafts and inferior turbinate reduction (Fig. 2B). Notably, the overlying soft tissue envelope and underlying mucosa were left intact; no iatrogenic or external nasal defect was created. The patient underwent a postoperative positron emission tomography-computed tomography (PET/CT), which was negative for metastases. He completed four cycles of adjuvant ipilimumab; however, further FoundationOne® genomic testing revealed the presence of an EWSR1-ATF1 translocation without a BRAF mutation and, as such, the diagnosis was amended to CCS. As no definitive or established adjuvant medical therapy exists, further treatment was suspended in favor of serial surveillance imaging. The patient remains clinically free of
Discussion CCS shares many pathologic and immunohistochemical similarities to melanoma including the presence of melanin, a propensity for nodal metastases, and positive staining for S-100 and HMB-45 [3]. Unlike malignant melanoma, CCS lacks the classic BRAF mutation and is characterized by a unique genetic translocation, t(12; 22), which results in the formation of a highly-specific EWSR1-ATF1 fusion gene [4]. Overall, CCS portends a poor prognosis. In most cases, CCS follows an aggressive clinical course and may quickly progress with late metastases being common even after several years of being disease-free, with the latest recurrence documented at 29 years.3 Studies have correlated a poor prognosis with the most important variable being tumor size ≥5 cm in addition to local recurrence and the presence of distant metastasis [5]. To date, limited reports of head and neck CCS have been described. A 2013 review by Inoue et al. found that only 4 of 696 (0.6%) CCS cases occurred within the head and neck [2]. Feasel and colleagues presented a small case series of 3 patients with a review of the literature and identified a total of 10 primary cases of head and neck CCS with sub2
Otolaryngology Case Reports 13 (2019) 100127
D.A. Silverman, et al.
resection and frequent surveillance are crucial in order to detect the presence of late and distant metastases.
sites including the mandible, tongue, scalp, face, cheek, and lip [1]. Similarly, unusual cases of metastases to the nasal soft tissue envelope have been reported including clear cell renal cell carcinoma, papillary thyroid carcinoma, and testicular natural killer T-cell lymphoma (NKTCL) [6–8]. To the authors’ knowledge, our case is the first known report of primary clear cell sarcoma arising within the nasal soft tissue envelope. Despite the largely asymptomatic presentation of the nasal mass in our patient, the final pathologic diagnosis highlights the need to maintain a high index of suspicion for more insidious pathology in similar cases involving otherwise benign features. Although the total number of benign cases is likely significantly underreported as cases like epidermoid cysts are not being documented, it is important to note that uncommon pathology may occur within the soft tissue envelope, whether benign or malignant. In similar cases, patients may present primarily to the otolaryngologist or facial plastic surgeon and may be referred by dermatologists requesting excision for largely aesthetic and possibly functional purposes. The current case highlights the importance of balancing these goals which may be complicated in similar instances where the chance for malignancy is not initially suspected but ultimately discovered. As such, a thorough discussion of the wide differential of these lesions and contingencies for addressing malignant potential is warranted as the cosmetic and functional results may be complicated by the need for complete surgical resection and adjuvant therapy for these patients. Obtaining a biopsy for preoperative diagnosis is paramount and, in the event of a nondiagnostic result, a second or confirmatory biopsy may be indicated; however, this was not attempted in our patient. Although observation with serial examination and/or imaging may be warranted or preferred by the patient, surgical excision of a nasal soft tissue mass is generally recommended for diagnostic and therapeutic benefit. Three main approaches are recommended and include direct excision, open rhinoplasty, and a closed/endonasal rhinoplasty approach. Patient anatomy dictates technique selection with more severe deformities or larger masses ≥1.0–1.5 cm well-suited for an external approach and enhances the ability of the surgeon to achieve an en-bloc tumor resection while optimizing exposure to aid in the correction of the resulting functional and aesthetic deficits. The closed or endonasal rhinoplasty approach may be indicated in select cases; however, this technique is less amenable in the setting of larger lesions as the ease of resection increases in complexity. Moreover, the endonasal approach may complicate the successful en-bloc removal of these masses and the subsequent reconstruction of these defects, especially in cases where the chance for malignancy persists. From an oncologic perspective, complete surgical resection with tumor-free margins is required for curative intent in cases of clearly defined malignancy. Therefore, if concerns for potential malignancy are present, an open rhinoplasty approach is likely the safer strategy. Limited studies have explored the role of adjuvant chemotherapy and radiation following resection of CCS; however, results have been varied without a definitive consensus [5,9]. Nonetheless, complete
Conclusion CCS is a rare but aggressive tumor with limited head and neck presentations. A high index of suspicion for the possibility of malignant pathology in otherwise benign-appearing masses should be maintained. An external rhinoplasty approach may be best suited in order to achieve not only complete, en-bloc resection but also to correct functional deficits and maximize aesthetic results. Disclosures Note: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest None. Sponsorships None. Funding sources None. References [1] Feasel PC, Cheah AL, Fritchie K, Winn B, Piliang M, Billings SD. Primary clear cell sarcoma of the head and neck: a case series with review of the literature. J Cutan Pathol 2016;43:838–46. [2] Inoue S, Chepeha DB, Lucas DR, Faisal S, Stewart RC, Mushtaq R, et al. Clear cell sarcoma of the jaw: a case report and review of the literature. Int J Pediatr Hematol Oncol 2013;35:402–5. [3] Chung EB, Enzinger FM. Malignant melanoma of soft parts. A reassessment of clear cell sarcoma. Am J Surg Pathol 1983;7:405–13. [4] Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM, Baelde JJ, Hogendoorn PC. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Canc 2001;84:535–8. [5] Ferrari A, Casanova M, Bisogno G, Mattke A, Meazza C, Gandola L, et al. Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 2002;94:3269–76. [6] Cui P, Cong X, Yin J, Liu M, Wang X, Yang L, et al. Metastases to the nose from clear cell renal cell carcinoma: a case report. Medicine 2019;98:e14012. [7] Khan OA, Roses DF, Peck V. Papillary thyroid carcinoma metastatic to skin may herald aggressive disease. Endocr Pract: Off J Am College Endocrinol Am Assoc Clin Endocrinol 2010;16:446–8. [8] Naboush A, Farhat F, Nasser SM, Kamar FG. Bifocal presentation of primary testicular extranasal NK/T-Cell lymphoma: a case report and review of the literature. Case Rep Oncol Med 2013;2013. 267389. [9] Malchau SS, Hayden J, Hornicek F, Mankin HJ. Clear cell sarcoma of soft tissues. J Surg Oncol 2007;95:519–22.
3