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Plasmacytoma of the larynx
AM ER IC AN JOUR NA L OF OTOLARYNGO LOGY –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
Available online at www.sciencedirect.com
www.elsevier.com/locate/amjoto
Plasmacytoma of the larynx Myriam Loyo, MDa , Alex Baras, MD, PhDb , Lee M. Akst, MDa,⁎ a
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
b
ARTI CLE I NFO
A BS TRACT
Article history:
Amyloid is an extracellular proteinaceous low-molecular-weight fibril. In the larynx,
Received 10 October 2012
amyloid deposits usually represent a benign localized disease. Although laryngeal amyloidosis is an indolent lesion, amyloid deposition in the larynx may actually result from a lymphoproliferative disorder and not isolated amyloidosis. In this case report, we describe a patient referred for laryngeal amyloidosis who was subsequently diagnosed with extramedullary plasmacytoma of the larynx. The report discusses the presentation, diagnosis, and treatment provided. The importance of systemic workup and accurate tissue diagnosis in differentiating primary amyloidosis and secondary amyloid deposition will be highlighted. © 2013 Elsevier Inc. All rights reserved.
1.
Introduction
Amyloidosis, the extracellular accumulation of proteinaceous low-molecular-weight fibrils, is generally uncommon in upper aerodigestive structures. Amyloid accounts for 0.1%–1.2% of benign laryngeal lesions [1]. Laryngeal amyloidosis is usually localized and rarely part of systemic disease [2]. However, some cases of laryngeal amyloidosis can be secondary processes resulting from lymphoid neoplastic processes, neuroendocrine carcinomas, or inflammatory conditions, making careful investigation important. In this case report, we describe a patient referred for laryngeal amyloidosis who was subsequently diagnosed with extramedullary plasmacytoma of the larynx. The report discusses the presentation, pathologic diagnosis, and treatment provided. The different prognosis and management for isolated laryngeal amyloidosis and secondary amyloidosis will be highlighted in the discussion. The Johns Hopkins Medical Institution Review Board approved this report.
2.
Case report
An 80-year-old female was referred for management of laryngeal amyloidosis. She had a 2-year history of progressive hoarseness leading to increased vocal effort and vocal strain. She denied breathing or swallowing difficulties. The referring physician had noted right paraglottic fullness and biopsy revealed laryngeal amyloidosis. The patient's past medical history includes hypertension, osteoarthritis, obesity, cardiac arrhythmia, and hemithyroidectomy. Work-up for systemic amyloidosis with computed tomography of chest/abdomen/ pelvis, serum and urine protein electrophoresis, and immunoelectrophoresis was negative. Upon presentation to our clinic, laryngeal stroboscopy revealed right paraglottic fullness and convex right vocal fold contour. Ipsilateral mucosal waveforms were greatly reduced, and contact of the convex right vocal fold against the left vocal fold also deformed left mucosal waveforms. Remaining head and neck examination was unremarkable. Initially, she elected conservative follow-up for her isolated voice
⁎ Corresponding author. Department of Otolaryngology- Head and Neck Surgery, Johns Hopkins University, 601 N. Caroline Street Suite 6260, Baltimore, MD 21287, USA. Tel.: + 1 410 955 1654; fax: +1 410 955 0035. E-mail address: [email protected] (L.M. Akst). 0196-0709/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjoto.2012.11.003
AM ERI CAN JOUR NAL OF OTOLARY NG OLOG Y –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
complaints. As the lesion enlarged on serial exam, and as voice got worse, microlaryngeal surgery for lesion debulking was discussed; unfortunately, the patient was then lost to follow-up for several months secondary to co-morbid conditions. Upon re-presentation, she described increasing exertional dyspnea with rare inspiratory stridor. On stroboscopy, the right-sided fullness had greatly increased in size, with effacement of the right false as well as true vocal cord (Fig. 1). Microlaryngeal surgery with flexible CO2 laser (OmniGuide, Cambridge, MA) allowed submucosal debulking of disease from the right hemilarynx. A firm mass extended from the right false vocal fold level through the laryngeal ventricle and into the paraglottic space through the true vocal fold's superior surface. Debulking of the right paraglottic space preserved the true vocal fold medial edge. Pathologic evaluation revealed plasmacytoma with extensive amyloid deposition, CD38-immunoreactivy, and kappa lightchain restriction. Ki-67 immunostaining demonstrated low proliferation index. Congo red staining showed apple-green birefringence under polarized light, characteristic of amyloid deposition (Fig. 2). Post-operative evaluation showed adequate healing with improved laryngeal symmetry and recovery of vocal fold
Fig. 1 – Pre-operative still pictures from video stroboscopy revealing in abduction (A) and adduction (B) showing right paraglottic fullness and displacement of the right true vocal cord medially resulting in a convex vocal fold contour and impingement on the contra lateral vocal cord.
173
mobility. Voice complaints were very much improved; overall degree of vocal roughness was improved and her voice was less effortful and strained. Dyspnea and stridor had resolved. Further hematologic work up including PET/CT scan performed in light of the new diagnosis of plasmacytoma did not reveal any evidence of systemic disease. Chemotherapy was offered to the patient by her medical oncologist, though in light of negative PET/CT scan and her age, the patient elected for observation reserving adjuvant therapy for disease progression.
3.
Discussion
Isolated laryngeal amyloidosis represents a different biological process than secondary amyloidosis. There are several systemic diseases that can lead to increased production and subsequent tissue deposition of light chain immunoglobulins. Some of the more common examples include immunologic dyscrasias like multiple myeloma or chronic inflammatory conditions like rheumatoid arthritis. Localized amyloidosis on the other hand appears to be an isolated pathology with a single site being involved. Although localized amyloidosis is rare, the larynx is the most common site affected [1]. Clinical and laboratory assessments are used to look for underlying systemic disease. Radiologic chest x-rays and skeletal surveys are often employed. Laboratory studies include liver and renal function tests, serology for rheumatoid arthritis, quantitative immunoglobulin and electrophoresis assays in serum and urine, and Bence-Jones protein analysis. Bone marrow biopsies are commonly utilized to rule out lymphoid malignancies. Medullary carcinoma of the thyroid should also be excluded. Extramedullary plasmacytomas are a rare pathology representing 3% of all plasma cell neoplasms and less than 1% of head and neck tumors [3]. They represent localized malignant plasma cell tumors that secondarily lead to amyloid deposition. Recognizing the monoclonal nature of plasmacytic tumor within amyloid deposition constitutes the challenge in diagnosing laryngeal plasmacytomas. In cases of localized amyloid disease without malignancy, identifying numerous plasma cells is common. However, these cells are typically polyclonal, excluding the diagnosis of malignancy. In this case, even though extensive amyloid deposition was noted, pathology revealed monoclonal plasma cell proliferation. Extramedullary plasmacytoma is sub-classified based on a three tier histologic grading—low, intermediate, and high grade based on degree of cellular atypia. After plasmacytoma has been identified histologically, exclusion of systemic disease must follow. Extramedullary plasmacytoma is indolent in nature and is considered a low-grade lymphoma or a mucosal-associated lymphoid tissue (MALT) lymphoma; however, recurrence and transformation to an aggressive phenotype has been described. Management of laryngeal amyloidosis is conservative with endoscopic removal as necessary based on local symptoms yielding satisfactory results and slow progression of the disease [1]. Resections are conservative and intended to preserve laryngeal function. In contrast, extramedullary
174
AM ER IC AN JOUR NA L OF OTOLARYNGO LOGY –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
Fig. 2 – (A) Atypical plasma cell proliferation associated with extensive amyloid deposition, hematoxylin-eosin (original magnification × 64). (B-C) Congo red staining with (C) and without (B) polarizing light (original magnification × 64). (D-E) Immunostains demonstrating kappa light chain restriction (D kappa light chain, E lambda light chain). (F) CD38 immunoreactivity. (G) Ki-67 immunostaining demonstrates a low proliferation index (original magnification ×64).
AM ERI CAN JOUR NAL OF OTOLARY NG OLOG Y –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
plasmacytomas can exhibit local recurrence seen in up to 30% of cases and even conversion to multiple myelomas in 15% of patients [4]. Given the high risk of recurrence and malignant transformation systemic surveillance is necessary and adjuvant therapy considered. Excellent local control rates have been reported for extramedullary plasmacytoma with the combination of surgery and radiotherapy, with better locoregional control observed in patients treated with both modalities [4]. Surgery in these cases aims to remove the lesion in its entirety. Plasmacytomas are highly radiosensitive and usual treatment doses are 40–60 Gy. Long-term follow-up for patients with laryngeal plasmocytoma is advocated for local and systemic surveillance.
4.
Conclusion
Isolated laryngeal amyloidosis represents a rare indolent process and often represents a localized, primary process. However, laryngeal amyloidosis may also be secondary to an underlying malignancy or systemic disease such as plasma-
175
cytoma. Recognition of the difference between primary and secondary laryngeal amyloid deposition has important clinical consequences for recurrence rate and recommended care. Therefore, careful tissue diagnosis and work up for systemic disease are mandatory in all cases of laryngeal amyloidosis. The presence of monoclonal lymphoid processes should heighten suspicion for an underlying process.
REFERENCES
[1] Thompson LD, Derringer GA, Wenig BM. Amyloidosis of the larynx: a clinicopathologic study of 11 cases. Mod Pathol 2000;13:528–35. [2] Penner CR, Muller S. Head and neck amyloidosis: a clinicopathologic study of 15 cases. Oral Oncol 2006;42:421–9. [3] Saad R, Raab S, Liu Y, et al. Plasmacytoma of the larynx diagnosed by fine-needle aspiration cytology: a case report. Diagn Cytopathol 2001;24:408–11. [4] Alexiou C, Kau RJ, Dietzfelbinger H, et al. Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 1999;85:2305–14.
Available online at www.sciencedirect.com
www.elsevier.com/locate/amjoto
Plasmacytoma of the larynx Myriam Loyo, MDa , Alex Baras, MD, PhDb , Lee M. Akst, MDa,⁎ a
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
b
ARTI CLE I NFO
A BS TRACT
Article history:
Amyloid is an extracellular proteinaceous low-molecular-weight fibril. In the larynx,
Received 10 October 2012
amyloid deposits usually represent a benign localized disease. Although laryngeal amyloidosis is an indolent lesion, amyloid deposition in the larynx may actually result from a lymphoproliferative disorder and not isolated amyloidosis. In this case report, we describe a patient referred for laryngeal amyloidosis who was subsequently diagnosed with extramedullary plasmacytoma of the larynx. The report discusses the presentation, diagnosis, and treatment provided. The importance of systemic workup and accurate tissue diagnosis in differentiating primary amyloidosis and secondary amyloid deposition will be highlighted. © 2013 Elsevier Inc. All rights reserved.
1.
Introduction
Amyloidosis, the extracellular accumulation of proteinaceous low-molecular-weight fibrils, is generally uncommon in upper aerodigestive structures. Amyloid accounts for 0.1%–1.2% of benign laryngeal lesions [1]. Laryngeal amyloidosis is usually localized and rarely part of systemic disease [2]. However, some cases of laryngeal amyloidosis can be secondary processes resulting from lymphoid neoplastic processes, neuroendocrine carcinomas, or inflammatory conditions, making careful investigation important. In this case report, we describe a patient referred for laryngeal amyloidosis who was subsequently diagnosed with extramedullary plasmacytoma of the larynx. The report discusses the presentation, pathologic diagnosis, and treatment provided. The different prognosis and management for isolated laryngeal amyloidosis and secondary amyloidosis will be highlighted in the discussion. The Johns Hopkins Medical Institution Review Board approved this report.
2.
Case report
An 80-year-old female was referred for management of laryngeal amyloidosis. She had a 2-year history of progressive hoarseness leading to increased vocal effort and vocal strain. She denied breathing or swallowing difficulties. The referring physician had noted right paraglottic fullness and biopsy revealed laryngeal amyloidosis. The patient's past medical history includes hypertension, osteoarthritis, obesity, cardiac arrhythmia, and hemithyroidectomy. Work-up for systemic amyloidosis with computed tomography of chest/abdomen/ pelvis, serum and urine protein electrophoresis, and immunoelectrophoresis was negative. Upon presentation to our clinic, laryngeal stroboscopy revealed right paraglottic fullness and convex right vocal fold contour. Ipsilateral mucosal waveforms were greatly reduced, and contact of the convex right vocal fold against the left vocal fold also deformed left mucosal waveforms. Remaining head and neck examination was unremarkable. Initially, she elected conservative follow-up for her isolated voice
⁎ Corresponding author. Department of Otolaryngology- Head and Neck Surgery, Johns Hopkins University, 601 N. Caroline Street Suite 6260, Baltimore, MD 21287, USA. Tel.: + 1 410 955 1654; fax: +1 410 955 0035. E-mail address: [email protected] (L.M. Akst). 0196-0709/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjoto.2012.11.003
AM ERI CAN JOUR NAL OF OTOLARY NG OLOG Y –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
complaints. As the lesion enlarged on serial exam, and as voice got worse, microlaryngeal surgery for lesion debulking was discussed; unfortunately, the patient was then lost to follow-up for several months secondary to co-morbid conditions. Upon re-presentation, she described increasing exertional dyspnea with rare inspiratory stridor. On stroboscopy, the right-sided fullness had greatly increased in size, with effacement of the right false as well as true vocal cord (Fig. 1). Microlaryngeal surgery with flexible CO2 laser (OmniGuide, Cambridge, MA) allowed submucosal debulking of disease from the right hemilarynx. A firm mass extended from the right false vocal fold level through the laryngeal ventricle and into the paraglottic space through the true vocal fold's superior surface. Debulking of the right paraglottic space preserved the true vocal fold medial edge. Pathologic evaluation revealed plasmacytoma with extensive amyloid deposition, CD38-immunoreactivy, and kappa lightchain restriction. Ki-67 immunostaining demonstrated low proliferation index. Congo red staining showed apple-green birefringence under polarized light, characteristic of amyloid deposition (Fig. 2). Post-operative evaluation showed adequate healing with improved laryngeal symmetry and recovery of vocal fold
Fig. 1 – Pre-operative still pictures from video stroboscopy revealing in abduction (A) and adduction (B) showing right paraglottic fullness and displacement of the right true vocal cord medially resulting in a convex vocal fold contour and impingement on the contra lateral vocal cord.
173
mobility. Voice complaints were very much improved; overall degree of vocal roughness was improved and her voice was less effortful and strained. Dyspnea and stridor had resolved. Further hematologic work up including PET/CT scan performed in light of the new diagnosis of plasmacytoma did not reveal any evidence of systemic disease. Chemotherapy was offered to the patient by her medical oncologist, though in light of negative PET/CT scan and her age, the patient elected for observation reserving adjuvant therapy for disease progression.
3.
Discussion
Isolated laryngeal amyloidosis represents a different biological process than secondary amyloidosis. There are several systemic diseases that can lead to increased production and subsequent tissue deposition of light chain immunoglobulins. Some of the more common examples include immunologic dyscrasias like multiple myeloma or chronic inflammatory conditions like rheumatoid arthritis. Localized amyloidosis on the other hand appears to be an isolated pathology with a single site being involved. Although localized amyloidosis is rare, the larynx is the most common site affected [1]. Clinical and laboratory assessments are used to look for underlying systemic disease. Radiologic chest x-rays and skeletal surveys are often employed. Laboratory studies include liver and renal function tests, serology for rheumatoid arthritis, quantitative immunoglobulin and electrophoresis assays in serum and urine, and Bence-Jones protein analysis. Bone marrow biopsies are commonly utilized to rule out lymphoid malignancies. Medullary carcinoma of the thyroid should also be excluded. Extramedullary plasmacytomas are a rare pathology representing 3% of all plasma cell neoplasms and less than 1% of head and neck tumors [3]. They represent localized malignant plasma cell tumors that secondarily lead to amyloid deposition. Recognizing the monoclonal nature of plasmacytic tumor within amyloid deposition constitutes the challenge in diagnosing laryngeal plasmacytomas. In cases of localized amyloid disease without malignancy, identifying numerous plasma cells is common. However, these cells are typically polyclonal, excluding the diagnosis of malignancy. In this case, even though extensive amyloid deposition was noted, pathology revealed monoclonal plasma cell proliferation. Extramedullary plasmacytoma is sub-classified based on a three tier histologic grading—low, intermediate, and high grade based on degree of cellular atypia. After plasmacytoma has been identified histologically, exclusion of systemic disease must follow. Extramedullary plasmacytoma is indolent in nature and is considered a low-grade lymphoma or a mucosal-associated lymphoid tissue (MALT) lymphoma; however, recurrence and transformation to an aggressive phenotype has been described. Management of laryngeal amyloidosis is conservative with endoscopic removal as necessary based on local symptoms yielding satisfactory results and slow progression of the disease [1]. Resections are conservative and intended to preserve laryngeal function. In contrast, extramedullary
174
AM ER IC AN JOUR NA L OF OTOLARYNGO LOGY –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
Fig. 2 – (A) Atypical plasma cell proliferation associated with extensive amyloid deposition, hematoxylin-eosin (original magnification × 64). (B-C) Congo red staining with (C) and without (B) polarizing light (original magnification × 64). (D-E) Immunostains demonstrating kappa light chain restriction (D kappa light chain, E lambda light chain). (F) CD38 immunoreactivity. (G) Ki-67 immunostaining demonstrates a low proliferation index (original magnification ×64).
AM ERI CAN JOUR NAL OF OTOLARY NG OLOG Y –H EA D A N D N EC K ME D IC IN E AN D S U RG ER Y 34 ( 20 1 3 ) 1 7 2–1 7 5
plasmacytomas can exhibit local recurrence seen in up to 30% of cases and even conversion to multiple myelomas in 15% of patients [4]. Given the high risk of recurrence and malignant transformation systemic surveillance is necessary and adjuvant therapy considered. Excellent local control rates have been reported for extramedullary plasmacytoma with the combination of surgery and radiotherapy, with better locoregional control observed in patients treated with both modalities [4]. Surgery in these cases aims to remove the lesion in its entirety. Plasmacytomas are highly radiosensitive and usual treatment doses are 40–60 Gy. Long-term follow-up for patients with laryngeal plasmocytoma is advocated for local and systemic surveillance.
4.
Conclusion
Isolated laryngeal amyloidosis represents a rare indolent process and often represents a localized, primary process. However, laryngeal amyloidosis may also be secondary to an underlying malignancy or systemic disease such as plasma-
175
cytoma. Recognition of the difference between primary and secondary laryngeal amyloid deposition has important clinical consequences for recurrence rate and recommended care. Therefore, careful tissue diagnosis and work up for systemic disease are mandatory in all cases of laryngeal amyloidosis. The presence of monoclonal lymphoid processes should heighten suspicion for an underlying process.
REFERENCES
[1] Thompson LD, Derringer GA, Wenig BM. Amyloidosis of the larynx: a clinicopathologic study of 11 cases. Mod Pathol 2000;13:528–35. [2] Penner CR, Muller S. Head and neck amyloidosis: a clinicopathologic study of 15 cases. Oral Oncol 2006;42:421–9. [3] Saad R, Raab S, Liu Y, et al. Plasmacytoma of the larynx diagnosed by fine-needle aspiration cytology: a case report. Diagn Cytopathol 2001;24:408–11. [4] Alexiou C, Kau RJ, Dietzfelbinger H, et al. Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 1999;85:2305–14.