- Email: [email protected]
Castleman Disease of the Parotid Gland: A Case Report
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PATHOLOGY
Castleman Disease of the Parotid Gland: A Case Report
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Liu Xiao-dong, DDS,* Wang Qiu-xu, DDS, PhD,y and Liu Wei-xian, DDS, PhDz
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Castleman disease is a rare lymphoproliferative disorder characterized by the formation of painless hyperplastic lymph nodes. It can affect any lymph nodes of the body but rarely affects the salivary gland. We describe a patient with unicentric Castleman disease presenting as a parotid tumor and discuss the diagnosis and treatment of Castleman disease. A 39-year-old man had a painless lump on the right side of his face for 1 year. A computed tomography scan showed a well-defined, homogeneous mass in the right parotid gland. The patient underwent a right-sided superficial parotidectomy with preservation of the facial nerve. Histopathologic analysis of the excisional biopsy specimen confirmed the diagnosis of Castleman disease. No further treatment was administered, and the patient recovered well; no recurrence was present at the 1-year follow-up. Castleman disease is a lymphoproliferative disease that rarely affects the parotid gland. Histopathologic examination is regarded as the gold standard for diagnosis of Castleman disease. The current treatment for patients with unicentric Castleman disease is surgical resection. For patients with multicentric Castleman disease, more complex therapies are required. Ó 2019 Published by Elsevier Inc. on behalf of the American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1.e1-1.e6, 2019 Castleman disease (CD) is a benign lymphoproliferative disorder with unclear pathogenesis.1 CD was first identified in 1954 by Benjamin Castleman.2 It has been referred to by different names including giant lymph node hyperplasia, benign giant lymphoma, angiofollicular lymph node hyperplasia, and lymphoid hamartoma. CD can affect any lymph node in the body, including the head and neck region. However, the parotid gland is rarely affected.3 On the basis of histologic assessment, CD is classified into 3 subtypes: hyaline vascular, plasma cell, and mixed. On the basis of clinical assessment, CD is classified into unicentric and multicentric forms. The unicentric form is typically characterized by the appearance of an asymptomatic painless mass, and surgical excision is generally the first choice for treatment of such a mass. Currently, there are no established guidelines for the treatment of multicentric Castleman disease (MCD).4 The diagnosis of CD remains challenging for clinicians,
A 39-year-old man presented to our hospital with a history of a painless lump on the right side of his face for the past 1 year. Physical examination showed a nontender, well-circumscribed rubbery lump (3.0 2.0 cm) in the right parotid region (Fig 1). No palpable lymph nodes were found, and there was no
Received from Department of Oral and Maxillofacial Surgery,
China Medical University, No. 36 Sanhao Street, Heping District She-
Shengjing Hospital, China Medical University, Shenyang, China.
nyang 110004, Liaoning, China; e-mail: [email protected]
especially when patients present with unicentric Castleman disease (UCD) because it has no specific clinical or radiologic features; thus, histopathologic examination is regarded as the gold standard for diagnosis of UCD. Because CD rarely affects the parotid region, there have been few studies regarding CD in the parotid region. In this article, we present a case of CD affecting the parotid gland. The patient underwent a right-sided superficial parotidectomy; no recurrence was found during the 1-year follow-up period.
Case Report
*Resident. yProfessor.
Received September 30 2019 Accepted November 12 2019
zProfessor.
Ó 2019 Published by Elsevier Inc. on behalf of the American Association of Oral
Conflict of Interest Disclosures: None of the authors have any
and Maxillofacial Surgeons
relevant financial relationship(s) with a commercial interest.
0278-2391/19/31335-7
Address correspondence and reprint requests to Dr Xiao-dong:
https://doi.org/10.1016/j.joms.2019.11.008
Department of Oral and Maxillofacial Surgery, Shengjing Hospital,
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CASTLEMAN DISEASE OF PAROTID GLAND
FIGURE 3. The removed mass had a red-tan appearance with localized fat-like tissue. Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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FIGURE 1. Preoperative clinical photograph. Physical examination showed a nontender, 3.0 2.0–cm well-circumscribed rubbery lump in the right parotid region. Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
sign of facial nerve involvement. A computed tomography (CT) scan showed a well-defined, homogeneous mass in the right parotid gland, which measured 3.7 2.9 cm (Fig 2). However, a definitive diagnosis could not be achieved. By April 2018, the patient underwent a right-sided superficial parotidectomy with preservation of the facial nerve for diagnostic and curative purposes. During surgery, this lesion was found within an intraparotid lymph node in the region of the tail of the parotid. The removed mass had a red-tan appearance (Fig 3). After surgery, the patient recovered well and exhibited no complications. Histopathologic analysis Q5 showed the presence of lymphoid follicular hyperplasia and vascular proliferation in the 1) interfollicular region, 2) involuted and hyalinized germinal centers, 3) expanded mantle zones with concentric layering of small lymphocytes that exhibited a classic ‘‘onionskin’’ appearance, and 4) follicular germinal center cells of CD that were replaced by follicular dendritic cells; these characteristics confirmed the
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FIGURE 2. Computed tomography scan showing a homogeneous mass in the right parotid gland.
FIGURE 4. Microscopic examination showing prominent hyalinization around a vessel (black arrows) and a vessel entering the germinal center (red arrow) (hematoxylin-eosin stain, original magnification 100).
Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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FIGURE 5. Microscopic examination showing the onion-skin appearance of the mantle zone (black arrows) and a vessel entering the germinal center (red arrows) (hematoxylin-eosin stain, original magnification 200). Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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diagnosis of hyaline vascular CD (Figs 4-6). CD21 immunohistochemical staining results also supported the diagnosis. After surgery, a full-body scan and bone marrow biopsy were performed, which ruled out the presence of a multicentric form of CD. No further treatment was administered, and the patient recovered well. Follow-up evaluations were performed via parotid CT scans at 6-month intervals; no recurrence was present at the 1-year follow-up.
Discussion The pathogenesis of CD is not yet well understood. Some studies have shown that CD involves an immunologic response leading to excessive hyperplasia of plasma cells and B cells due to nonspecific inflammatory reactions of lymph nodes.5 In addition, several viral infections (eg, Epstein-Barr virus, human immunodeficiency virus, and human herpesvirus 8 [HHV-8]) have been associated with the onset of CD.6 In a related manner, CD has
been closely associated with interleukin (IL) 6 and tumor necrosis factor a.3 Clinical manifestations of CD have been classified into unicentric and multicentric forms. The unicentric form (UCD) is typically found in young adults and manifests as an asymptomatic painless mass.7 The multicentric form (MCD) is often associated with systemic symptoms, is poorly diagnosed, and typically affects middle-aged men. This form involves growths at multiple sites. Patients with MCD typically show symptoms of fever, weight loss, fatigue, night sweats, weakness, and fluid retention.8 MCD can ultimately progress to malignancies such as Hodgkin lymphoma, non-Hodgkin lymphoma, or Kaposi sarcoma.9 These systemic symptoms are caused by excess IL-6 production from B cells and the actions of HHV-8. Associated oral erosive lichen planus and pemphigus also have been reported in patients with MCD.10 CD can be histologically divided into 3 types: hyaline vascular, plasma cell, and mixed. The hyaline vascular type is present in more than 90% of patients with CD and is typically found in patients with a diagnosis of UCD,11 which commonly affects a single lymph node. It is characterized by the presence of lymphoid follicles surrounded by concentric layering of lymphocytes, which results in expansion of the mantle zone with an onion-skin appearance. Histologically, the plasma cell type is characterized by proliferation of plasma cells in the interfollicular region. This type is typically found in patients with a diagnosis of MCD and is clinically aggressive.12 Although CD can be found in any region in the body, 70% of patients exhibit CD in the mediastinum; more than 20% of patients exhibit CD in the head and neck region.13 However, parotid gland involvement is rarely reported. In this report, we have reviewed the literature regarding patients with parotid gland involvement in CD and analyzed the clinical characteristics of their cases (Table 1).3,4,7,14-28 In our review,
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XIAO-DONG, QIU-XU, AND WEI-XIAN
FIGURE 6. High-power histo-photomicrographs showing concentric layering of small lymphocytes (arrow) (A) and replacement of follicular germinal center cells by follicular dendritic cells (arrow) (B) (hematoxylin-eosin stain, original magnification 400). Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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Table 1. PRIOR REPORTS OF CASTLEMAN DISEASE INVOLVING PAROTID GLAND
Reference
Age, yr/Gender
3
46/F
4
14/M
7
19/M
14
7/M
14
11/F
15
34/F
16
36/M
17
35/F
18
16/M
19
66/M
19
19/M
20
9/M
21
5/F
22
17/M
23
9/F
24
46/F
25
19/M
26
16/F
27
41/F
28
18/F
Clinical Symptom Painless left-sided facial mass for 1 yr Painless right-sided facial mass for 1 yr Painless left-sided facial mass for 8 mo Painless right-sided facial mass for 1 yr Asymptomatic rightsided facial mass for 3 yr No symptoms Painless left-sided facial mass Painless right-sided facial mass Painless right-sided facial mass for 1 yr Painless left-sided facial mass for 3 yr Painless right-sided facial mass for 3 mo Painless left-sided facial mass for 3 mo Painless left-sided facial mass for 2 yr Painless right-sided facial mass for 2 yr Painless right-sided facial mass for 1 yr Painless left-sided facial mass for 3 yr Painless left-sided facial mass for 9 yr Painless left-sided facial mass for 2 yr Painless left-sided facial mass Painless left-sided facial mass for 1 mo
Treatment Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Total parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy
Pathology
Prognosis
UCD (hyaline vascular)
Recovered well without complications Recovered well
UCD (hyaline vascular type) CD (hyaline vascular) CD (hyaline vascular) CD (hyaline vascular)
CD (hyaline vascular)
Recovered well No evidence of recurrence at 6 mo No evidence of recurrence at 1 yr
CD (hyaline vascular)
No evidence of recurrence at 8 mo Recovered well
CD (hyaline vascular)
Recovered well
CD (hyaline vascular)
CD (hyaline vascular)
No evidence of recurrence at 1 yr No evidence of recurrence at 5 yr No evidence of recurrence at 14 mo No evidence of recurrence at 1 yr No evidence of recurrence at 2 yr Recovered well
CD (hyaline vascular)
Recovered well
CD (hyaline vascular) CD (hyaline vascular)
No evidence of recurrence at 9 yr Recovered well
CD (hyaline vascular)
Recovered well
CD (hyaline vascular)
No evidence of recurrence at 9 mo Recovered well
CD (hyaline vascular) CD (hyaline vascular) CD (hyaline vascular) CD (hyaline vascular)
CD (hyaline vascular)
Abbreviations: CD, Castleman disease; F, female; M, male; UCD, unicentric Castleman disease. Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
we found 20 patients, many of whom were young adults. Surgical excision was the most common method of treatment, and most patients exhibited the hyaline vascular type of CD. The diagnosis of CD is difficult because this disease has no specific clinical or radiographic manifestations, which has resulted in a lack of diagnostic biomarkers. CD can be easily confused with other lesions in the head and neck region, including lymphoma, branchial cleft
cyst, lymphangioma, Kaposi sarcoma, hemangioma, and metastatic nodes.29 Histopathologic examination remains the gold standard for diagnosis, especially for UCD, because of the lack of specific signs or symptoms. Fine-needle aspiration biopsy can aid in Q7 the diagnosis of CD. Some reports described the diagnosis of lymphoid hyperplasia by fine-needle aspiration biopsy before surgical excision of the mass.17-22 However, for most patients, fine-needle aspiration
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biopsy is inconclusive and can only narrow the differential diagnosis; it does not provide a definitive diagnosis. In some instances, preoperative fine-needle aspiration biopsy has led to a misdiagnosis, such as Warthin tumor.24,30 Radiologic examinations can be helpful but are not conclusive for the diagnosis of CD. CT scans typically show a well-circumscribed, homogeneous mass with moderate to intense contrast enhancement. HHV-8 has been associated with MCD and localized CD.18 Therefore, laboratory test findings can be useful for diagnosis; however, the HHV-8 viral load was not assessed in our patient. Overall, postoperative histopathologic examination remains the preferred approach for a definitive diagnosis. The treatment of CD is selected based on histologic type. Complete surgical excision is the first choice for patients with the hyaline vascular type; the 5-year control rate is 100% after surgical excision of this type of CD in the head and neck.31 For patients who cannot undergo surgical excision, radiation therapy can be effective.32 After complete resection of the mass, the prognosis of UCD is always good and patients experience no recurrence.24,27 However, failure to completely remove the lesion results in a significant increase in the mortality rate from UCD.33 There are many options for treatment of MCD but no official guidelines thus far. Therapies for MCD include chemotherapy, immunosuppressive therapy, radiotherapy, and corticosteroid therapy3; chemotherapy combined with steroid therapy is the most common treatment approach. In recent years, overproduction of IL-6 has been shown to play an important role in the pathogenesis of MCD, although the specific mechanism is not well understood.34 In the future, the long-term safety and specific mechanisms of IL-6 inhibitor treatment should be further studied.35 Patients with MCD have a poor prognosis, and long-term follow-up is important in these patients because of the possibility of malignant transformation. The 10-year survival rate for patients with MCD is only 48.2%, whereas it is 95% for patients with UCD.33 In conclusion, CD is a lymphoproliferative disease that rarely affects the parotid gland. Diagnosing this disease is a substantial challenge because of the lack of specific clinical manifestations. The unicentric form is difficult to differentiate from other benign lesions in the parotid region, such as Warthin tumor and pleomorphic adenoma. Histopathologic examination is considered the gold standard for the diagnosis of CD, and current treatment of UCD consists of surgical resection. For MCD, more complex therapies and long-term follow-up are required. Although CD is rarely encountered in the parotid gland, clinicians should consider the possibility of CD when a lymphoproliferative lesion is present in the parotid gland.
References 1. Schulte KM, Talat N: Castleman’s disease—A two compartment model of HHV8 infection. Nat Rev Clin Oncol 7:533, 2010 2. Castleman B, Iverson L, Menendez VP: Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer 9:822, 1956 3. Reece B, Ord R, Papadimitriou J: Rare presentation of unicentric Castleman’s disease in the parotid gland. J Oral Maxillofac Surg 70:2114, 2012 4. Bollig C, Moon S, Sujoy V, Younis R: Castleman disease of the parotid in childhood: A case report. Am J Otolaryngol 35:517, 2014 5. Keller AR, Hochholzer L, Castleman B: Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 29:670, 1972 6. Beukes CA, Thiart J: The incidence of human herpes virus-8 expression in lymph node biopsies from human immunodeficiency virus-positive patients. Histopathology 61:942, 2012 7. Kilty SJ, Yammine NV, Corsten MJ, et al: Castleman’s disease of the parotid. J Otolaryngol 33:396, 2004 8. Bonekamp D, Horton KM, Hruban RH, Fishman EK: Castleman disease: The great mimic. Radiographics 31:1793, 2011 9. Hayashi M, Aoshiba K, Shimada M, et al: Kaposi’s sarcomaassociated herpesvirus infection in the lung in multicentric Castleman’s disease. Intern Med 38:279, 1999 10. Ashinoff R, Cohen R, Lipkin G: Castleman’s tumor and erosive lichen planus: Coincidence or association? Report of a case. J Am Acad Dermatol 21:1076, 1989 11. Nahlieli O, Hasson O, Ben-Dor D, Goupil MT: Rapidly growing mass in the parotid gland. J Oral Maxillofac Surg 58:552, 2000 12. Weisenburger DD, Nathwani BN, Winberg CD, Rappaport H: Multicentric angiofollicular lymph node hyperplasia: A clinicopathologic study of 16 cases. Hum Pathol 16:162, 1985 13. Frizzera G, Peterson BA, Bayrd ED, Goldman A: A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease: Clinical findings and clinicopathologic correlations in 15 patients. J Clin Oncol 3:1202, 1985 14. Delaney SW, Zhou S, Maciri D: Castleman’s disease presenting as a parotid mass in the pediatric population: A report of 2 cases. Case Rep Otolaryngol 2015:691701, 2015 15. G€ urb€ uzler L, Ceylan A, Yilmaz M, Vural C: Castleman’s disease of the parotid gland: A case report. Kaohsiung J Med Sci 26: 444, 2010 16. Goodisson DW, Carr RJ, Stirling RW: Parotid presentation of Castleman’s disease: Report of a case. J Oral Maxillofac Surg 55:515, 1997 17. Iaconetta G, Friscia M, Dell’Aversana OG, et al: Castleman’s disease mimicking a parotid gland tumor: Report of a case and review of the literature. Eur Rev Med Pharmacol Sci 18:1241, 2014 18. Caselli E, Padovani D, Di Carlo R: Parotid localized Castleman’s disease and HHV-8 infection: A case report. Eur Arch Otorhinolaryngol 265:377, 2008 19. Sanchez-Cuellar A, Pedro MD, Martin-Granizo R, Berguer A: Castleman disease (giant lymph node hyperplasia) in the maxillofacial region: A report of 3 cases. J Oral Maxillofac Surg 59:228, 2001 20. Park JH, Lee SW, Koh YW: Castleman disease of the parotid gland in childhood: An unusual entity. Auris Nasus Larynx 35: 451, 2008 21. Santonja CJ, Garcia-Aroca J, Colomar PJ: Castleman’s disease and lymphoepithelial cysts of the parotid in childhood. Histopathology 30:369, 1997 22. Mohan H, Bal A, Tahlan A: Images in pathology—Castleman’s disease of the parotid. J Postgrad Med 49:348, 2003 23. Udaquiola JE, Liberto DH, Kreindel TG, et al: Cervical Castleman’s disease. Pediatric case report. Arch Argent Pediatr 111: 89, 2013 (in Spanish) 24. Jiang L, Zhao LY, Liu Y, Zhao YF: Castleman’s disease of the neck: Report of 4 cases with unusual presentations. J Oral Maxillofac Surg 69:1094, 2011 25. Mahmood N, Suresh HB, Swethadri GK, et al: Ultrasound and Doppler findings in a rare case of Castleman’s disease of the parotid. Dentomaxillofac Radiol 39:54, 2010
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26. Tan TY, Pang KP, Goh HKC, et al: Castleman’s disease of the neck: A description of four cases on contrast-enhanced CT. Br J Radiol 77:253, 2004 27. Song JJ, Jung MH, Woo JS, et al: Castleman’s disease of the head and neck. Eur Arch Otorhinolaryngol 263:160, 2006 28. Lin CY, Chang YL: Castleman’s disease in the head and neck region: Meta-analysis of reported cases in Taiwan and literature review. J Formos Med Assoc 109:913, 2010 29. Erdogan F, Altas S, Altas E, et al: A rare location of Castleman’s disease: Parotid region. N Z Med J 121:86, 2008 30. Yi AY, de Tar M, Becker TS, Rice DH: Giant lymph node hyperplasia of the head and neck (Castleman’s disease): A report of five cases. Otolaryngol Head Neck Surg 113:462, 1995 31. Bowne WB, Lewis JJ, Filippa DA, et al: The management of unicentric and multicentric Castleman’s disease: A report of
32.
33.
34.
35.
16 cases and a review of the literature. Cancer 85:706, 1999 Chronowski GM, Ha CS, Wilder RB, et al: Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. Cancer 92:670, 2001 Talat N, Belgaumkar AP, Schulte KM: Surgery in Castleman’s disease: A systematic review of 404 published cases. Ann Surg 255: 677, 2012 Van Rhee F, Fayad L, Voorhees P, et al: Siltuximab, a novel antiinterleukin-6 monoclonal antibody, for Castleman’s disease. J Clin Oncol 28:3701, 2010 Tomohiro K, Remi S, Atsushi K, Kazuyuki Y: A benefit and the prospects of IL-6 inhibitors in idiopathic multicentric Castleman’s disease. Mod Rheumatol 29: 302, 2019
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PATHOLOGY
Castleman Disease of the Parotid Gland: A Case Report
Q1
Liu Xiao-dong, DDS,* Wang Qiu-xu, DDS, PhD,y and Liu Wei-xian, DDS, PhDz
Q12
Q3
Q4
Castleman disease is a rare lymphoproliferative disorder characterized by the formation of painless hyperplastic lymph nodes. It can affect any lymph nodes of the body but rarely affects the salivary gland. We describe a patient with unicentric Castleman disease presenting as a parotid tumor and discuss the diagnosis and treatment of Castleman disease. A 39-year-old man had a painless lump on the right side of his face for 1 year. A computed tomography scan showed a well-defined, homogeneous mass in the right parotid gland. The patient underwent a right-sided superficial parotidectomy with preservation of the facial nerve. Histopathologic analysis of the excisional biopsy specimen confirmed the diagnosis of Castleman disease. No further treatment was administered, and the patient recovered well; no recurrence was present at the 1-year follow-up. Castleman disease is a lymphoproliferative disease that rarely affects the parotid gland. Histopathologic examination is regarded as the gold standard for diagnosis of Castleman disease. The current treatment for patients with unicentric Castleman disease is surgical resection. For patients with multicentric Castleman disease, more complex therapies are required. Ó 2019 Published by Elsevier Inc. on behalf of the American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1.e1-1.e6, 2019 Castleman disease (CD) is a benign lymphoproliferative disorder with unclear pathogenesis.1 CD was first identified in 1954 by Benjamin Castleman.2 It has been referred to by different names including giant lymph node hyperplasia, benign giant lymphoma, angiofollicular lymph node hyperplasia, and lymphoid hamartoma. CD can affect any lymph node in the body, including the head and neck region. However, the parotid gland is rarely affected.3 On the basis of histologic assessment, CD is classified into 3 subtypes: hyaline vascular, plasma cell, and mixed. On the basis of clinical assessment, CD is classified into unicentric and multicentric forms. The unicentric form is typically characterized by the appearance of an asymptomatic painless mass, and surgical excision is generally the first choice for treatment of such a mass. Currently, there are no established guidelines for the treatment of multicentric Castleman disease (MCD).4 The diagnosis of CD remains challenging for clinicians,
A 39-year-old man presented to our hospital with a history of a painless lump on the right side of his face for the past 1 year. Physical examination showed a nontender, well-circumscribed rubbery lump (3.0 2.0 cm) in the right parotid region (Fig 1). No palpable lymph nodes were found, and there was no
Received from Department of Oral and Maxillofacial Surgery,
China Medical University, No. 36 Sanhao Street, Heping District She-
Shengjing Hospital, China Medical University, Shenyang, China.
nyang 110004, Liaoning, China; e-mail: [email protected]
especially when patients present with unicentric Castleman disease (UCD) because it has no specific clinical or radiologic features; thus, histopathologic examination is regarded as the gold standard for diagnosis of UCD. Because CD rarely affects the parotid region, there have been few studies regarding CD in the parotid region. In this article, we present a case of CD affecting the parotid gland. The patient underwent a right-sided superficial parotidectomy; no recurrence was found during the 1-year follow-up period.
Case Report
*Resident. yProfessor.
Received September 30 2019 Accepted November 12 2019
zProfessor.
Ó 2019 Published by Elsevier Inc. on behalf of the American Association of Oral
Conflict of Interest Disclosures: None of the authors have any
and Maxillofacial Surgeons
relevant financial relationship(s) with a commercial interest.
0278-2391/19/31335-7
Address correspondence and reprint requests to Dr Xiao-dong:
https://doi.org/10.1016/j.joms.2019.11.008
Department of Oral and Maxillofacial Surgery, Shengjing Hospital,
1.e1 CRP 5.6.0 DTD YJOMS58972_proof 11 December 2019 11:44 am CE KO
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CASTLEMAN DISEASE OF PAROTID GLAND
FIGURE 3. The removed mass had a red-tan appearance with localized fat-like tissue. Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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FIGURE 1. Preoperative clinical photograph. Physical examination showed a nontender, 3.0 2.0–cm well-circumscribed rubbery lump in the right parotid region. Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
sign of facial nerve involvement. A computed tomography (CT) scan showed a well-defined, homogeneous mass in the right parotid gland, which measured 3.7 2.9 cm (Fig 2). However, a definitive diagnosis could not be achieved. By April 2018, the patient underwent a right-sided superficial parotidectomy with preservation of the facial nerve for diagnostic and curative purposes. During surgery, this lesion was found within an intraparotid lymph node in the region of the tail of the parotid. The removed mass had a red-tan appearance (Fig 3). After surgery, the patient recovered well and exhibited no complications. Histopathologic analysis Q5 showed the presence of lymphoid follicular hyperplasia and vascular proliferation in the 1) interfollicular region, 2) involuted and hyalinized germinal centers, 3) expanded mantle zones with concentric layering of small lymphocytes that exhibited a classic ‘‘onionskin’’ appearance, and 4) follicular germinal center cells of CD that were replaced by follicular dendritic cells; these characteristics confirmed the
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FIGURE 2. Computed tomography scan showing a homogeneous mass in the right parotid gland.
FIGURE 4. Microscopic examination showing prominent hyalinization around a vessel (black arrows) and a vessel entering the germinal center (red arrow) (hematoxylin-eosin stain, original magnification 100).
Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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FIGURE 5. Microscopic examination showing the onion-skin appearance of the mantle zone (black arrows) and a vessel entering the germinal center (red arrows) (hematoxylin-eosin stain, original magnification 200). Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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diagnosis of hyaline vascular CD (Figs 4-6). CD21 immunohistochemical staining results also supported the diagnosis. After surgery, a full-body scan and bone marrow biopsy were performed, which ruled out the presence of a multicentric form of CD. No further treatment was administered, and the patient recovered well. Follow-up evaluations were performed via parotid CT scans at 6-month intervals; no recurrence was present at the 1-year follow-up.
Discussion The pathogenesis of CD is not yet well understood. Some studies have shown that CD involves an immunologic response leading to excessive hyperplasia of plasma cells and B cells due to nonspecific inflammatory reactions of lymph nodes.5 In addition, several viral infections (eg, Epstein-Barr virus, human immunodeficiency virus, and human herpesvirus 8 [HHV-8]) have been associated with the onset of CD.6 In a related manner, CD has
been closely associated with interleukin (IL) 6 and tumor necrosis factor a.3 Clinical manifestations of CD have been classified into unicentric and multicentric forms. The unicentric form (UCD) is typically found in young adults and manifests as an asymptomatic painless mass.7 The multicentric form (MCD) is often associated with systemic symptoms, is poorly diagnosed, and typically affects middle-aged men. This form involves growths at multiple sites. Patients with MCD typically show symptoms of fever, weight loss, fatigue, night sweats, weakness, and fluid retention.8 MCD can ultimately progress to malignancies such as Hodgkin lymphoma, non-Hodgkin lymphoma, or Kaposi sarcoma.9 These systemic symptoms are caused by excess IL-6 production from B cells and the actions of HHV-8. Associated oral erosive lichen planus and pemphigus also have been reported in patients with MCD.10 CD can be histologically divided into 3 types: hyaline vascular, plasma cell, and mixed. The hyaline vascular type is present in more than 90% of patients with CD and is typically found in patients with a diagnosis of UCD,11 which commonly affects a single lymph node. It is characterized by the presence of lymphoid follicles surrounded by concentric layering of lymphocytes, which results in expansion of the mantle zone with an onion-skin appearance. Histologically, the plasma cell type is characterized by proliferation of plasma cells in the interfollicular region. This type is typically found in patients with a diagnosis of MCD and is clinically aggressive.12 Although CD can be found in any region in the body, 70% of patients exhibit CD in the mediastinum; more than 20% of patients exhibit CD in the head and neck region.13 However, parotid gland involvement is rarely reported. In this report, we have reviewed the literature regarding patients with parotid gland involvement in CD and analyzed the clinical characteristics of their cases (Table 1).3,4,7,14-28 In our review,
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FIGURE 6. High-power histo-photomicrographs showing concentric layering of small lymphocytes (arrow) (A) and replacement of follicular germinal center cells by follicular dendritic cells (arrow) (B) (hematoxylin-eosin stain, original magnification 400). Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
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Table 1. PRIOR REPORTS OF CASTLEMAN DISEASE INVOLVING PAROTID GLAND
Reference
Age, yr/Gender
3
46/F
4
14/M
7
19/M
14
7/M
14
11/F
15
34/F
16
36/M
17
35/F
18
16/M
19
66/M
19
19/M
20
9/M
21
5/F
22
17/M
23
9/F
24
46/F
25
19/M
26
16/F
27
41/F
28
18/F
Clinical Symptom Painless left-sided facial mass for 1 yr Painless right-sided facial mass for 1 yr Painless left-sided facial mass for 8 mo Painless right-sided facial mass for 1 yr Asymptomatic rightsided facial mass for 3 yr No symptoms Painless left-sided facial mass Painless right-sided facial mass Painless right-sided facial mass for 1 yr Painless left-sided facial mass for 3 yr Painless right-sided facial mass for 3 mo Painless left-sided facial mass for 3 mo Painless left-sided facial mass for 2 yr Painless right-sided facial mass for 2 yr Painless right-sided facial mass for 1 yr Painless left-sided facial mass for 3 yr Painless left-sided facial mass for 9 yr Painless left-sided facial mass for 2 yr Painless left-sided facial mass Painless left-sided facial mass for 1 mo
Treatment Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Total parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy Superficial parotidectomy
Pathology
Prognosis
UCD (hyaline vascular)
Recovered well without complications Recovered well
UCD (hyaline vascular type) CD (hyaline vascular) CD (hyaline vascular) CD (hyaline vascular)
CD (hyaline vascular)
Recovered well No evidence of recurrence at 6 mo No evidence of recurrence at 1 yr
CD (hyaline vascular)
No evidence of recurrence at 8 mo Recovered well
CD (hyaline vascular)
Recovered well
CD (hyaline vascular)
CD (hyaline vascular)
No evidence of recurrence at 1 yr No evidence of recurrence at 5 yr No evidence of recurrence at 14 mo No evidence of recurrence at 1 yr No evidence of recurrence at 2 yr Recovered well
CD (hyaline vascular)
Recovered well
CD (hyaline vascular) CD (hyaline vascular)
No evidence of recurrence at 9 yr Recovered well
CD (hyaline vascular)
Recovered well
CD (hyaline vascular)
No evidence of recurrence at 9 mo Recovered well
CD (hyaline vascular) CD (hyaline vascular) CD (hyaline vascular) CD (hyaline vascular)
CD (hyaline vascular)
Abbreviations: CD, Castleman disease; F, female; M, male; UCD, unicentric Castleman disease. Xiao-dong, Qiu-xu, and Wei-xian. Castleman Disease of Parotid Gland. J Oral Maxillofac Surg 2019.
we found 20 patients, many of whom were young adults. Surgical excision was the most common method of treatment, and most patients exhibited the hyaline vascular type of CD. The diagnosis of CD is difficult because this disease has no specific clinical or radiographic manifestations, which has resulted in a lack of diagnostic biomarkers. CD can be easily confused with other lesions in the head and neck region, including lymphoma, branchial cleft
cyst, lymphangioma, Kaposi sarcoma, hemangioma, and metastatic nodes.29 Histopathologic examination remains the gold standard for diagnosis, especially for UCD, because of the lack of specific signs or symptoms. Fine-needle aspiration biopsy can aid in Q7 the diagnosis of CD. Some reports described the diagnosis of lymphoid hyperplasia by fine-needle aspiration biopsy before surgical excision of the mass.17-22 However, for most patients, fine-needle aspiration
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biopsy is inconclusive and can only narrow the differential diagnosis; it does not provide a definitive diagnosis. In some instances, preoperative fine-needle aspiration biopsy has led to a misdiagnosis, such as Warthin tumor.24,30 Radiologic examinations can be helpful but are not conclusive for the diagnosis of CD. CT scans typically show a well-circumscribed, homogeneous mass with moderate to intense contrast enhancement. HHV-8 has been associated with MCD and localized CD.18 Therefore, laboratory test findings can be useful for diagnosis; however, the HHV-8 viral load was not assessed in our patient. Overall, postoperative histopathologic examination remains the preferred approach for a definitive diagnosis. The treatment of CD is selected based on histologic type. Complete surgical excision is the first choice for patients with the hyaline vascular type; the 5-year control rate is 100% after surgical excision of this type of CD in the head and neck.31 For patients who cannot undergo surgical excision, radiation therapy can be effective.32 After complete resection of the mass, the prognosis of UCD is always good and patients experience no recurrence.24,27 However, failure to completely remove the lesion results in a significant increase in the mortality rate from UCD.33 There are many options for treatment of MCD but no official guidelines thus far. Therapies for MCD include chemotherapy, immunosuppressive therapy, radiotherapy, and corticosteroid therapy3; chemotherapy combined with steroid therapy is the most common treatment approach. In recent years, overproduction of IL-6 has been shown to play an important role in the pathogenesis of MCD, although the specific mechanism is not well understood.34 In the future, the long-term safety and specific mechanisms of IL-6 inhibitor treatment should be further studied.35 Patients with MCD have a poor prognosis, and long-term follow-up is important in these patients because of the possibility of malignant transformation. The 10-year survival rate for patients with MCD is only 48.2%, whereas it is 95% for patients with UCD.33 In conclusion, CD is a lymphoproliferative disease that rarely affects the parotid gland. Diagnosing this disease is a substantial challenge because of the lack of specific clinical manifestations. The unicentric form is difficult to differentiate from other benign lesions in the parotid region, such as Warthin tumor and pleomorphic adenoma. Histopathologic examination is considered the gold standard for the diagnosis of CD, and current treatment of UCD consists of surgical resection. For MCD, more complex therapies and long-term follow-up are required. Although CD is rarely encountered in the parotid gland, clinicians should consider the possibility of CD when a lymphoproliferative lesion is present in the parotid gland.
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