A Plasmacytoma of the Lateral Pharyngeal Wall: A Diagnostic Enigma

Abstract

Plasmacytoma is a rare plasma cell dyscrasia that grows in bones or soft tissues such as the pharynx. Soft tissue plasmacytomas are rare, and a higher burden has been reported in the upper aero-digestive tract, often manifesting as hoarseness, dysphagia, or odynophagia. Due to their rarity, extramedullary plasmacytomas (EMPs) have unknown prognostic factors, and guidelines for optimal management are still lacking. However, radiation therapy and surgery have been used with positive outcomes. Herein, we describe a unique case of plasmacytoma of the pharyngeal tissue in a male patient with a history of HIV disease. The patient completed 28 sessions of radiation therapy, resulting in an improvement in his throat pain and hoarseness. Given the patient’s age and lack of traditional risk factors for head and neck cancers, his hoarseness and odynophagia proved to be a diagnostic conundrum. Although infrequent, soft tissue plasmacytomas should be considered in the differential diagnosis of head and neck tumors.

Introduction

First described by Schridde et al in 1905, an extramedullary plasmacytoma (EMP) is a rare neoplastic lesion characterized by the monoclonal proliferation of plasma cells in soft tissue.^1-4 Extramedullary plasmacytomas constitute 3% of all plasmacytomas and less than 1% of all head and neck tumors.^1,4-6 Plasmacytomas most commonly occur in men in their late 50s or older and are usually found in the upper aero-digestive tract, especially the nasal cavity, nasopharynx, and oropharynx.^2,5,7,8 Extramedullary plasmacytomas of the lungs, digestive tract, skin, lymph nodes, and extremities have also been reported.^1,3 Although plasmacytomas are typically solitary lesions, they can sometimes progress to multiple myeloma, a more serious condition involving the systemic spread of plasma cells to the bone marrow and other organs.^2,3 Fortunately, solitary plasmacytomas are usually curable with radiation therapy, unlike multiple myeloma, which requires chemotherapy. Complete surgical excision can also be curative for some plasmacytomas.^2,3,8 Albeit infrequent, plasmacytomas should be included in the differential diagnosis of head and neck masses. ⁴ Herein, we present a rare case of plasmacytoma of the pharyngeal tissue in a male patient with a history of HIV disease. An incisional biopsy of the lesion confirmed the diagnosis, and the patient completed 28 sessions of radiation therapy. The patient’s odynophagia and throat pain have improved, and he continues to benefit from speech therapy for his hoarseness.

Case Report

A 48-year-old male with a medical history of HIV disease, hyperlipidemia, and hypertension presented to the infectious disease clinic complaining of progressively worsening hoarseness for approximately 2 months. The patient initially attributed the change in voice to the SARS-COV-2 viral infection he had the year prior, but became worried when the hoarseness worsened. Hoarseness was associated with sharp stabbing pain in the right submandibular and peritonsillar areas. The pain was constant, rated 8/10 at its peak, but nonradiating. The patient also reported odynophagia, but denied nausea, vomiting, globus sensation, choking, excessive secretions, nocturnal dyspnea, fever, recent upper respiratory infection, or tobacco use. The patient was compliant with his HIV medication and had an absolute CD4 count of 633/mcL and an undetectable viral load. On physical examination, there was no pooling of secretions, pharyngeal erythema, masses, or palpable lymphadenopathy. The remainder of the physical examination was unremarkable and the vital signs were within normal ranges.

Due to concern for a head and neck tumor, the patient was subsequently referred to an Ear, Nose, and Throat (ENT) specialist for further evaluation. An indirect laryngoscopy was performed, which demonstrated normal vocal cord movement with no masses or tumors. The patient was started on 20 mg of omeprazole daily, with some lifestyle changes. One month later, he returned to the ENT clinic with no improvement in hoarseness or throat pain. Bloodwork, including a complete metabolic panel, complete blood count, hepatitis panel, uric acid, and lactate dehydrogenase, was unremarkable. A maxillofacial computed tomography (CT) scan with contrast showed no abnormalities. The omeprazole dose was increased to 40 mg daily, and the patient was referred to a gastroenterology clinic for further evaluation.

Esophagogastroduodenoscopy (EGD) with biopsy revealed mild bulbo-duodenitis and moderate antral gastritis. The pathology was positive for Helicobacter pylori bacteria, but there was no evidence of intestinal metaplasia or dysplasia. A colonoscopy was also performed, which revealed a single, small-mouthed diverticulum in the ascending colon. The patient completed a triple therapy regimen for H. pylori infection, but the hoarseness and throat pain persisted. The ENT surgeon re-evaluated the patient with a flexible fiber-optic laryngoscopy, which showed possible ulceration of the left vocal cord. Direct laryngoscopy was then scheduled, later revealing a pedunculated, circular cyst-like lesion in the right pharyngeal wall within the supraglottic space (Images unavailable). Another benign-appearing lesion was observed at the level of the glottis. Both lesions were biopsied, and the specimens were sent for histopathological analysis.

Surgical pathology of the right lateral pharyngeal wall lesion revealed a plasmacytic neoplasm favoring an EMP (Figure 1). On immunostaining, the tumor cells were positive for CD 138, MUM-1, CD 79a, and CD117 (Figure 2). The plasma cells were negative for CD20, PAX5, CD30, and EBER-ISH. On in situ hybridization, the plasma cells were monotypic for immunoglobulin (IgA) light chains kappa and negative for lambda (Figure 2). The pathology of the right vocal cord lesion revealed squamous mucosa with mostly reactive plasmatic infiltrates. Based on these findings, the right lateral pharyngeal wall tumor was diagnosed as plasmacytoma of pharyngeal tissue.

Figure 1.

Biopsy slides show a polypoid mass lined by benign squamous mucosa with underlying extensive proliferation of plasma cells. The plasma cells are mostly mature in appearance, but some plasma cells are mildly enlarged, and occasional plasma cells show plasmablastic morphology. Mitotic activities are present, but not risk.

Figure 2.

Immunostains demonstrated CD138 positivity (A), highlighting plasma cells. On in situ hybridization, the plasma cells were monotypic for immunoglobulin light chains kappa (B) and negative for lambda (C).

The oncology service evaluated the patient, and further workup was obtained. A positron emission tomography (PET) scan of the skull base to the mid-thigh revealed a small focal hypermetabolic malignant lesion in the right vocal cord of the larynx. There was no evidence of metastasis. Bone marrow biopsy showed 1% plasma cells with excess IgA. The plasma cells expressed CD38 bright, CD138, and showed a polytypic distribution of cytoplasmic kappa and lambda light chains. The cytogenetic results were normal. Serum and urine electrophoresis, and serum immunoelectrophoresis were unremarkable. The kappa/lambda ratio was 1.11, which is insufficient for the multiple myeloma criteria. The urine immunofixation showed no evidence for monoclonal protein or a polyclonal immunoglobulin pattern. The patient completed 28 sessions of 45-50 Gy radiation therapy for a plasmacytoma involving the right lateral pharyngeal wall in the supraglottic region. His throat pain and appetite have improved; however, he continues to experience hoarseness. The patient gets a repeat multiple myeloma workup at designated intervals and is pending a repeat direct laryngoscopy with a biopsy of the right vocal cord lesion.

Discussion

Plasmacytoma is a rare plasma cell dyscrasia that grows in bones or soft tissues such as the pharynx. ³ Soft tissue plasmacytomas are rare, and a higher burden has been reported in the upper aero-digestive tract, often manifesting as hoarseness, dysphagia, or odynophagia. ⁹ Extramedullary plasmacytomas affect mainly older males above the age of 50 years, but at least 5 cases involving pediatric patients have been reported.^2,7 Solitary EMPs in HIV-infected individuals are extremely rare and occur at younger ages (mean age 33 years).^10-13 A detailed literature search by Cao et al ¹¹ returned only 8 cases of EMP in patients with HIV disease. A handful of cases involving this patient cohort have been reported since then, including our patient. Notably, EMPs in these patients involve unique sites such as the adrenal glands, kidneys, ureter and omentum, and have a poor prognosis due to immunodeficiency.^10-14 It has been suggested that the HIV viral activity and the immunodeficiency in these patients puts them at risk of plasma cell dyscrasia.^11,14 There is a paucity of data on the epidemiology, pathogenesis, prognostic factors, and optimal management of solitary extraosseous plasmacytomas.^1,4,5 Nonetheless, an association with inhalation of noxious fumes, viral infections, and chronic irritation has been suggested. ² Here, we describe a rare case of plasmacytoma of pharyngeal tissue in a male patient with a history of HIV disease. Given the patient’s age and lack of traditional risk factors for head and neck cancers, his case proved to be a diagnostic puzzle.

Pharyngeal and laryngeal plasmacytomas can present with symptoms such as slowly progressive hoarseness, dysphonia, rhinorrhea, epistaxis, pain, dysphagia, stridor, hemoptysis, and choking sensations, especially in cases of locally aggressive tumors.^{1,3,4,7,8,15,16} Physical examination findings may include the presence of a mass or swelling in the pharyngeal region, erythema, or pooling if secretions. ⁸ However, it is important to note that physical examination alone is not sufficient for the diagnosis of pharyngeal plasmacytoma, and further diagnostic procedures such as fine-needle aspiration (FNA) biopsy or incisional biopsy are necessary for confirmation. ⁶

Extramedullary plasmacytoma is diagnosed through histopathological examination, which confirms the proliferation of neoplastic plasma cells. ¹⁷ Histological analysis shows deeply basophilic plasma cells with eccentric nuclei,^6,8 and immunohistochemical staining positive for CD138, CD79a, and lambda light chain (or kappa), confirming the monoclonal nature of cells. ⁵ Dual expression of the kappa and lambda immunoglobulins is extremely rare. ¹⁸ Systemic examinations are also conducted to rule out bone involvement, including bone surveys, chest X-rays, peripheral blood tests, and bone marrow biopsies.^9,17 Extramedullary plasmacytoma is distinct from solitary plasmacytoma of the bone and multiple myeloma, as it is usually a localized disease and associated with a favorable prognosis. ¹⁷ The diagnosis of EMP is based on the presence of neoplastic plasma cells in the soft tissues of the head and neck region, with the most common sites being the paranasal sinuses, nasal cavities, and nasopharynx.^2,4,15,17 Laryngeal and pharyngeal EMPs should be differentiated from laryngeal malignancies and benign tumors, such as laryngeal granuloma and papilloma, based on laryngoscopic findings.^4,17 The prognosis for EMP of the head and neck is generally better than that of solitary bone plasmacytoma or multiple myeloma, possibly due to early presentation and easy accessibility for examination.^15,17 In a systematic review of EMP case reports published between 1998 and 2021, Holler et al ¹ found that 76.9% of the patients had no local recurrence or transformation to multiple myeloma. Only 12.8% of the patients had local recurrence, and 10.2% developed multiple myeloma. ¹

Both the National Comprehensive Cancer Network (NCCN) panel and the European Expert panel recommend radiation therapy as primary treatment for solitary plasmacytomas.^19,20 This recommendation, however, is premised on results from retrospective studies and the optimal radiation dose is not yet known.^19,20 Extramedullary plasmacytomas are very radiosensitive tumors; therefore, radiotherapy is the most used treatment modality with a recommended radiation dose of 40-50 Guy at the primary site of the tumor.^1-3 Surgery involves resection of a mass or lesion using a carbon dioxide laser, which has a lower risk of bleeding or damage to the surrounding tissue.^1,2 Combined surgical excision and radiotherapy have superior outcomes compared to either modality alone.^1,2,16 Chemotherapy is mostly reserved for locally advanced, recurrent, and disseminated disease. ²¹ The 5-year survival rates for EMP range from 50% to 90% and the survival rate is mainly determined by progression to multiple myeloma over the next several months to years; hence, long-term follow-up is essential after treatment.^3,7,16,22

Conclusion

Extramedullary plasmacytomas are rare plasma cell neoplasms characterized by monoclonal proliferation of plasma cells in soft tissues. Often found in males in their 50s or older, pharyngeal EMPs can manifest as dysphonia, odynophagia, dysphagia, globus sensation, or airway obstruction. Extraosseous plasmacytomas are commonly treated with surgery or radiation therapy. Combined radiation and surgery have resulted in superior outcomes in most cases. Although rare, pharyngeal and laryngeal plasmacytomas should be considered in the differential diagnosis of head and neck masses.