CASE REPORT
Peter Andersen, MD, Section Editor
Very delayed cervical lymph node metastases from hyalinizing clear cell carcinoma: Report of 2 cases Henry K. Su, BA,1,2* Beverly Y. Wang, MD,3,4 Abul Ala Syed Rifat Mannan, MD,5 Eliza H. Dewey, BA,1,2 Erin H. Alpert, BA,1,2 Laura L. Dos Reis, BA,1,2 Mark L. Urken, MD2,4 1
Thyroid, Head and Neck Cancer (THANC) Foundation, New York, New York, 2Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Beth Israel, New York, New York, 3Department of Pathology, Mount Sinai Beth Israel, New York, New York, 4Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, 5Department of Pathology, Mount Sinai St. Luke’s Roosevelt, New York, New York..
Accepted 10 May 2014 Published online 19 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23764
ABSTRACT: Background. Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland neoplasm most often found in the oral cavity. Although it is generally a low-grade malignancy that is treated with wide local excision, there is a growing body of evidence pointing toward the potential for more aggressive behavior. Methods. We reviewed available records of patients with delayed cervical lymph node metastases from HCCC. Results. Two patients who were treated with wide local resection for HCCC and remained disease-free at the primary site were diagnosed with cervical lymph node metastases 10 and 14 years later. We treated
INTRODUCTION Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland neoplasm found nearly exclusively in the oral cavity. In a review of 200 cases of intraoral minor salivary gland cancers, Takahashi et al1 identified only 1 case (0.5%) of clear cell carcinoma. HCCC occurs predominantly in the minor salivary glands, and the most common sites of occurrence are the tongue and palate.2 HCCC has also been identified in the parotid gland.3,4 HCCC was first characterized as a distinct pathologic entity in 1994 by Milchgrub et al,5 who described it as a low-grade, monomorphic, glycogen-rich carcinoma with prominent stromal hyalinization. Although its histological appearance can vary widely, HCCC tends to be diagnosed on the basis of a distinctive pattern of clear cells forming cords and nests in a hyalinized stroma.6 The differential diagnosis can be difficult because the microscopic features of HCCC frequently overlap with other salivary gland tumors, and the most recent World Health Organization/International Agency for Research on Cancer classification of tumors from 2005 designates clear cell carcinomas “not otherwise
*Corresponding author: H. K. Su, Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Beth Israel, 10 Union Square East, Suite 5B, New York, NY 10003. E-mail: [email protected]
both with neck dissection, and 1 patient received adjuvant radiation therapy. Conclusion. These cases illustrate the risk for occult nodal metastases from HCCC with delayed presentation. Clinician awareness of the presence of subclinical metastases in the neck requires thorough long-term surveillance and potential intervention should nodal disease become C 2014 Wiley Periodicals, Inc. Head Neck 37: E19–E21, 2015 manifest. V
KEY WORDS: hyalinizing, clear cell carcinoma, salivary gland, delayed metastases, lymph node metastases
specified” and considers it a diagnosis of exclusion.7 However, recent genetic research has identified the consistent presence of EWSR1-ATF1 fusion in HCCC, providing a marker that may assist in differentiating it from other salivary neoplasms, such as epithelialmyoepithelial carcinoma and mucin-depleted mucoepidermoid carcinoma.8 Although HCCC is accepted as an overall indolent malignancy with favorable outcomes,6 sporadic case reports have noted examples of aggressive tumor behavior, such as rapid or repeated local recurrence and the development of pulmonary or osseous metastases.3,9,10 In a 2009 review of the literature, Solar et al2 reviewed 52 reported cases of HCCC in the English literature and discovered that, among these patients, 23% presented with evidence of metastatic spread and 11.5% developed recurrent disease after treatment. On the basis of these observations, they argued that HCCC may be a more biologically aggressive disease than previously thought. The purpose of this study was for us to report our experience with the long-term clinical follow-up of HCCC. We present 2 patients with HCCC who developed regional nodal metastases 10 and 14 years after their initial diagnosis and treatment. We believe that their clinical courses highlight the incompleteness in our current understanding of the biologic behavior of HCCC, elucidation of which is important for clinicians involved in the management of patients with these tumors. HEAD & NECK—DOI 10.1002/HED
FEBRUARY 2015
E19
SU ET AL.
MATERIALS AND METHODS Institutional review board approval for this retrospective review was obtained and the requirement for patient consent was waived. We performed a systematic chart review of 2 patients with HCCC who developed delayed nodal metastases after treatment of the primary tumor by the senior surgeon.
CASE REPORTS Case 1 A 37-year-old woman was diagnosed with a slowly progressing base-of-tongue tumor in 2002. At that time, the patient underwent a partial glossectomy with radial forearm free flap reconstruction. Negative resection margins were obtained using frozen section analysis. The patient tolerated the procedure well, and had an uneventful recovery. Pathologic assessment characterized the base of tongue lesion as a clear cell carcinoma of minor salivary gland origin. The tumor measured 2.4 cm in its greatest dimension. No lymphovascular invasion or perineural invasion were observed. Immunohistochemical stains revealed the tissue to be positive for cytokeratin AE1/AE3 but negative for actin, mucicarmine, carcinoembryonic antigen, calponin, and S-100 protein, supporting the diagnosis of clear cell carcinoma of salivary origin. There was no evidence of cervical lymph node involvement on CT imaging. She did not undergo an elective neck dissection or adjuvant therapy at that time. The patient was well and without evidence of disease until she returned 10 years later in 2012 with complaints of a nonpainful mass in the left side of her neck. A CT scan of the neck was obtained, which demonstrated a 2.5 cm heterogeneous lymph node in the left level II region. A fine-needle aspiration biopsy confirmed the presence of a low-grade adenocarcinoma. Accordingly, the patient underwent a left modified neck dissection and was found to have a 3.0-cm mass in the level II region. Surgical pathologic assessment demonstrated metastatic carcinoma with clear cell morphology in 2 upper neck lymph nodes. Focal extranodal extension was identified. Immunohistochemical stains returned positive for p63, high molecular weight cytokeratin, and negative for mucicarmine, carcinoembryonic antigen, calponin, vimentin, S100, smooth muscle actin, and CD10, compatible with metastatic HCCC. Postoperatively, the patient was treated with adjuvant external beam radiation therapy. A total of 5940 centigray of radiation was delivered in 33 doses to the left side of the neck. The patient demonstrated no evidence of recurrent disease on 1-year follow-up and has recovered well from the effects of surgery and radiation therapy.
Case 2 A 45-year-old woman was diagnosed with a palatal tumor in 1999 that measured
Peter Andersen, MD, Section Editor
Very delayed cervical lymph node metastases from hyalinizing clear cell carcinoma: Report of 2 cases Henry K. Su, BA,1,2* Beverly Y. Wang, MD,3,4 Abul Ala Syed Rifat Mannan, MD,5 Eliza H. Dewey, BA,1,2 Erin H. Alpert, BA,1,2 Laura L. Dos Reis, BA,1,2 Mark L. Urken, MD2,4 1
Thyroid, Head and Neck Cancer (THANC) Foundation, New York, New York, 2Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Beth Israel, New York, New York, 3Department of Pathology, Mount Sinai Beth Israel, New York, New York, 4Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, 5Department of Pathology, Mount Sinai St. Luke’s Roosevelt, New York, New York..
Accepted 10 May 2014 Published online 19 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23764
ABSTRACT: Background. Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland neoplasm most often found in the oral cavity. Although it is generally a low-grade malignancy that is treated with wide local excision, there is a growing body of evidence pointing toward the potential for more aggressive behavior. Methods. We reviewed available records of patients with delayed cervical lymph node metastases from HCCC. Results. Two patients who were treated with wide local resection for HCCC and remained disease-free at the primary site were diagnosed with cervical lymph node metastases 10 and 14 years later. We treated
INTRODUCTION Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland neoplasm found nearly exclusively in the oral cavity. In a review of 200 cases of intraoral minor salivary gland cancers, Takahashi et al1 identified only 1 case (0.5%) of clear cell carcinoma. HCCC occurs predominantly in the minor salivary glands, and the most common sites of occurrence are the tongue and palate.2 HCCC has also been identified in the parotid gland.3,4 HCCC was first characterized as a distinct pathologic entity in 1994 by Milchgrub et al,5 who described it as a low-grade, monomorphic, glycogen-rich carcinoma with prominent stromal hyalinization. Although its histological appearance can vary widely, HCCC tends to be diagnosed on the basis of a distinctive pattern of clear cells forming cords and nests in a hyalinized stroma.6 The differential diagnosis can be difficult because the microscopic features of HCCC frequently overlap with other salivary gland tumors, and the most recent World Health Organization/International Agency for Research on Cancer classification of tumors from 2005 designates clear cell carcinomas “not otherwise
*Corresponding author: H. K. Su, Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Beth Israel, 10 Union Square East, Suite 5B, New York, NY 10003. E-mail: [email protected]
both with neck dissection, and 1 patient received adjuvant radiation therapy. Conclusion. These cases illustrate the risk for occult nodal metastases from HCCC with delayed presentation. Clinician awareness of the presence of subclinical metastases in the neck requires thorough long-term surveillance and potential intervention should nodal disease become C 2014 Wiley Periodicals, Inc. Head Neck 37: E19–E21, 2015 manifest. V
KEY WORDS: hyalinizing, clear cell carcinoma, salivary gland, delayed metastases, lymph node metastases
specified” and considers it a diagnosis of exclusion.7 However, recent genetic research has identified the consistent presence of EWSR1-ATF1 fusion in HCCC, providing a marker that may assist in differentiating it from other salivary neoplasms, such as epithelialmyoepithelial carcinoma and mucin-depleted mucoepidermoid carcinoma.8 Although HCCC is accepted as an overall indolent malignancy with favorable outcomes,6 sporadic case reports have noted examples of aggressive tumor behavior, such as rapid or repeated local recurrence and the development of pulmonary or osseous metastases.3,9,10 In a 2009 review of the literature, Solar et al2 reviewed 52 reported cases of HCCC in the English literature and discovered that, among these patients, 23% presented with evidence of metastatic spread and 11.5% developed recurrent disease after treatment. On the basis of these observations, they argued that HCCC may be a more biologically aggressive disease than previously thought. The purpose of this study was for us to report our experience with the long-term clinical follow-up of HCCC. We present 2 patients with HCCC who developed regional nodal metastases 10 and 14 years after their initial diagnosis and treatment. We believe that their clinical courses highlight the incompleteness in our current understanding of the biologic behavior of HCCC, elucidation of which is important for clinicians involved in the management of patients with these tumors. HEAD & NECK—DOI 10.1002/HED
FEBRUARY 2015
E19
SU ET AL.
MATERIALS AND METHODS Institutional review board approval for this retrospective review was obtained and the requirement for patient consent was waived. We performed a systematic chart review of 2 patients with HCCC who developed delayed nodal metastases after treatment of the primary tumor by the senior surgeon.
CASE REPORTS Case 1 A 37-year-old woman was diagnosed with a slowly progressing base-of-tongue tumor in 2002. At that time, the patient underwent a partial glossectomy with radial forearm free flap reconstruction. Negative resection margins were obtained using frozen section analysis. The patient tolerated the procedure well, and had an uneventful recovery. Pathologic assessment characterized the base of tongue lesion as a clear cell carcinoma of minor salivary gland origin. The tumor measured 2.4 cm in its greatest dimension. No lymphovascular invasion or perineural invasion were observed. Immunohistochemical stains revealed the tissue to be positive for cytokeratin AE1/AE3 but negative for actin, mucicarmine, carcinoembryonic antigen, calponin, and S-100 protein, supporting the diagnosis of clear cell carcinoma of salivary origin. There was no evidence of cervical lymph node involvement on CT imaging. She did not undergo an elective neck dissection or adjuvant therapy at that time. The patient was well and without evidence of disease until she returned 10 years later in 2012 with complaints of a nonpainful mass in the left side of her neck. A CT scan of the neck was obtained, which demonstrated a 2.5 cm heterogeneous lymph node in the left level II region. A fine-needle aspiration biopsy confirmed the presence of a low-grade adenocarcinoma. Accordingly, the patient underwent a left modified neck dissection and was found to have a 3.0-cm mass in the level II region. Surgical pathologic assessment demonstrated metastatic carcinoma with clear cell morphology in 2 upper neck lymph nodes. Focal extranodal extension was identified. Immunohistochemical stains returned positive for p63, high molecular weight cytokeratin, and negative for mucicarmine, carcinoembryonic antigen, calponin, vimentin, S100, smooth muscle actin, and CD10, compatible with metastatic HCCC. Postoperatively, the patient was treated with adjuvant external beam radiation therapy. A total of 5940 centigray of radiation was delivered in 33 doses to the left side of the neck. The patient demonstrated no evidence of recurrent disease on 1-year follow-up and has recovered well from the effects of surgery and radiation therapy.
Case 2 A 45-year-old woman was diagnosed with a palatal tumor in 1999 that measured
