Palatine Tonsils Primary Presentation of Blastoid Variant of Mantle Cell Lymphoma: Case Report

Abstract

Head and neck lymphomas can present with a wide range of symptoms. Timely and accurate diagnosis is often challenging. The blastoid variant of mantle cell lymphoma (MCL) accounts for less than one-third of all MCL cases. Isolated primary presentation on the palatine tonsils is rare, and prognosis and outcome are seemingly unfavorable. An 81-year-old man presented with persistent odynophagia, dysphagia, and obstructive hypertrophic palatine tonsils with purulent exudate. The signs and symptoms were non-responsive to antibiotic therapy, and the tonsils were biopsied. The cellular morphology, immunophenotype, and genotype supported a diagnosis of the blastoid variant of MCL. After staging, the patient underwent chemotherapy with Rituximab-Bendamustine (R-Benda). The patient is in clinical remission more than two years after therapy. We report an exceedingly rare case of blastoid MCL that is prone to be misdiagnosed as tonsillitis. We review the literature and discuss treatment options of this uncommon malignancy.

Introduction

Lymphomas represent the third most frequent malignancy of the head and neck region (12%) following squamous cell carcinoma (46%) and thyroid carcinoma (33%) [1]. They are traditionally divided into Hodgkin’s (HL) or non-Hodgkin (NHL) lymphomas, and the latter are the most prevalent of all head and neck lymphomas [2, 3]. Head and neck NHL can present in nodal or extranodal forms [4, 5]. The Waldeyer’s ring is the most common site of involvement, accounting for more than half of extranodal head and neck lymphomas reported in the literature [6]. The ocular adnexa, nasal fossae, paranasal sinuses, oral cavity, and salivary glands are additional extranodal sites that may be involved by NHL [6, 7].

We report a unique case of a primary bilateral palatine tonsils involvement of the blastoid variant of mantle cell lymphoma (MCL).

Case Report

An 81-year-old male presented to our emergency department for persistent odynophagia, dysphagia, globus sensation, and progressive orthopnea of the preceding three weeks. He denied B symptoms of fever, night sweats, and weight loss. He was a non-smoker, non-drinker, and had no prior history of lymphoproliferative disorders, neoplasms, or radiation to the head and neck. Physical examination revealed grade IV tonsillar hypertrophy with purulent exudate (Fig. 1) and a hard, painless, right submandibular swelling that measured approximately 3 × 2 cm.

Fig. 1.

Clinical view of bilaterally hypertrophic palatine tonsils covered with purulent exudate with necrotic appearance

Flexible nasopharyngolaryngoscopy excluded pharyngeal tonsil enlargement and revealed significant oropharyngeal obstruction by the palatine tonsils.

Neck ultrasound examination showed multiple bilateral enlarged lymph nodes, suggestive of reactive lymph nodes, the largest located in the right submandibular area. Laboratory studies revealed normal leukocyte and differential blood cell counts, C-reactive protein, lactate dehydrogenase (LDH), and hepatic transaminases. Heterophil antibody test for infectious mononucleosis was negative. The patient was discharged from the hospital with a course of amoxicillin. At one week follow-up, there was no clinical improvement and the palatine tonsils were biopsied. The patient was referred to the Hemato-Oncology team for suspected lymphoproliferative disease.

Histopathologic examination demonstrated diffuse growth of a malignant proliferation beneath the remains of ulcerated tonsillar epithelium (Fig. 2). The cell population was composed of intermediate to large cells with irregular nuclei, occasional small nucleoli, and a high mitotic index. These findings were consistent with a lymphoproliferative disorder.

Fig. 2.

a Photomicrograph (hematoxylin–eosin, magnification × 100): Palatine tonsil extensively occupied by a lymphoid neoplasm and showing extensive surface ulceration. b Photomicrograph (hematoxylin–eosin, magnification × 200): The neoplasm was composed of irregularly sized cells with pleomorphic nuclei and occasional slits

Immunohistochemisty showed positivity for CD20, CD5, cyclin D1, and bcl-2 with a proliferative rate (Ki67 index) of approximately 80% (Fig. 3). Diagnosis of blastoid variant of MCL was established. Immunophenotyping of peripheral blood revealed an abnormal monoclonal lambda B cell population: CD5 + , CD20 + het, CD22 + , CD43 ± , CD79b + , IgM + , CD10-, CD11c-, CD23-, CD38-, CD103-. Cervico-thoraco-abdomino-pelvic computed tomography (CTAP) showed marked enlargement of the palatine tonsils and cervical, axillary, and inguinal lymphadenopathy. Bone marrow biopsy was negative for tumoral involvement.

Fig. 3.

a Immunohistochemistry showing diffuse expression of CD20 (magnification × 200), b Immunohistochemistry showing diffuse expression of CD5 (magnification × 200), c Immunohistochemistry showing expression of Cyclin D1 (magnification × 200) d Ki-67 immunostaining revealing high mitotic index (magnification × 100)

The patient was classified as high risk according to the MIPI-B (Biological Mantle Cell Lymphoma International Prognostic Index). He was treated with prednisolone and six courses of R-Benda (rituximab-bendamustine). After treatment, tonsillar hypertrophy and lymphadenopathies are significantly reduced (Fig. 4). The patient has been in clinical and imaging remission for more than two years.

Fig. 4.

Clinical view of the oropharynx after six cycles of R-Bendamustine

Discussion

Extranodal lymphomas of the head and neck are rare and represent a heterogeneous group of neoplasms. The natural history and treatment outcomes vary with histologic type, stage, and location of primary origin [3, 5, 7]. After the gastrointestinal tract, the head and neck region is the second most frequent site of extranodal lymphomas [6]. The most common site of extranodal lymphomas of Waldeyer’s ring is the palatine tonsils, followed by the nasopharynx [4, 7, 8].

Of all tonsillar B-cell NHLs, diffuse large B-cell lymphoma is the most common type, and MCL is less frequent [4, 5, 8]. MCL has been classically recognized as an aggressive and incurable small B-cell lymphoma that develops in a linear fashion from naïve B cells [9]. It accounts for 4% of all lymphomas in the United States and 7–9% in Europe [10]. Patients with MCL are usually in their 6^th decade of life and predominantly male (2:1) [11, 12]. They generally present with extensive lymphadenopathy, splenomegaly, peripheral blood, and bone marrow involvement [13, 14]. Other extranodal sites include the gastrointestinal tract, Waldeyer’s ring, skin, lacrimal glands, and central nervous system [12].

The diagnosis of MCL is established on a biopsy of a lymph node, tissue, bone marrow, or blood that demonstrates the classical morphology of monomorphic, small to medium sized lymphoid cells with irregular nuclear contours [11]. Immunophenotypic study is usually positive for CD5, CD19, CD20 and FMC and negative for CD10, CD23 and Bcl-6 [11, 15, 16]. The chromosomal translocation t(11:14)(q13;32) is present in most cases. This translocation leads to aberrant expression of the cyclin D oncogene which can be used to aid diagnosis [11, 15]. Four cytologic variants of MCL are recognized: the small cell variant, mantle zone variant, diffuse variant, and the blastoid variant [11, 15].

The blastoid variant is associated with aggressive disease and poor prognosis [17]. It accounts for approximately 20% to 30% of all MCL cases and usually arises de novo, although less frequently it may develop as a transformation from classical MCL [16, 18, 19]. This MCL variant is typically seen in men in their 6^th decade of life but may affect younger patients [15, 17, 20]. It has a high mitotic activity and proliferative index in approximately half of cases, compared to about a quarter in classic MCL, and is intimately associated with other molecular abnormalities such as p53 mutations and p16 deletions [20, 21]. Patients with the blastoid variant may present with circulating lymphoma cells, extensive leukocytosis, and a predisposition to central nervous system involvement. Therefore, cerebrospinal fluid analysis and central nervous system prophylaxis may be considered in patients with blastoid variant of MCL [15, 22, 23]. Nevertheless, data on the efficacy of intrathecal prophylaxis or systemic treatment with methotrexate or high-dose cytarabine are inconclusive [23, 24].

The blastoid variant with circulating lymphoma cells should be distinguished from B-cell acute lymphoblastic leukemia/lymphoma (ALL), minimally differentiated acute myeloblastic leukemia (AML, M0), and other high grade CD5 + and CD10 + NHLs [15, 20]. Histologically, the blastoid variant mimics ALL with monomorphic sheets of small to medium-sized blastic cells containing finely dispersed chromatin and a narrow rim of cytoplasm [13]. Contrary to ALL, blastoid variant expresses immunoglobulin light chain and B-lineage antigens on the surface and is negative for immature nuclear antigens such as terminal deoxynucleotidyl transferase (TdT) [22]. AML expresses pan-myeloid antigens (CD13, CD33) [25].

Although NHL is a common malignancy presenting within the head and neck, involvement of this region by MCL is unusual [26]. According to Hart et al., MCL represents 3% of all tonsillar lymphomas [27]. Aguilera et al., described 3 cases of blastoid variant of MCL located in the Waldeyer’s ring [28]. Contrary to the cases reported, our patient had bilateral involvement of palatine tonsils with a clinical presentation resembling infectious pharyngotonsillitis.

The diagnosis of tonsillar NHL may be challenging because patients’ complaints and physical findings can mimic conditions such as inflammatory/infectious pathology, granulomatous diseases, or, the most common malignancy of the tonsils, squamous cell carcinoma. Older age and prolonged or worsening of symptoms under antibiotic therapy should increase the level of suspicion for a neoplasm, immunological cause, or rarer infectious etiologies.

In our patient, the morphologic findings and immunophenotypic pattern of the neoplastic lymphocytes were essential for diagnosis. Facing diagnostic options that show common microscopic features, adequate immunophenotyping/genotyping was necessary to establish an accurate diagnosis and promptly commence treatment.

The survival of patients with MCL has considerably improved since the recognition of this lymphoma as a distinct entity [2]. A subset of patients with MCL who present with splenomegaly, blood and bone-marrow involvement have an unusually indolent course and can be followed without therapy [29]. Additionally, given the unfavorable prognosis and the fact that standard therapy does not appear to cure patients with MCL, a “watchful waiting” strategy in asymptomatic, low MIPI (Mantle Cell Lymphoma International Prognostic Index) or elderly MCL patients should be considered [11]. Nevertheless, most patients with MCL require therapy soon after diagnosis. Common treatment protocols include rituximab plus chemotherapy (CHOP – cyclophosphamide, doxorubicin, vincristine, and prednisone) or bortezomib instead of vincristine, bendamustine, and various regimens including high-dose cytarabine [30–33]. Moreover, new drugs and treatment approaches are currently being developed, such as lenalidomide plus rituximab (overall response rate of 92% and complete response rate of 64%) and ibrutinib combined with rituximab and bendamustine (overall response rate of 72% and complete response rate of 52%) [34, 35]. Although optimal treatment for blastoid variant of MCL remains to be established, more intensive approaches seem intuitive in patients who can tolerate such therapies since it appears to have a poorer response as compared to classical MCL [15].

To the best of our knowledge, this is the first case of primary presentation of blastoid variant of MCL in both palatine tonsils ever reported. The similarity between oropharyngeal infections and lymphoproliferative disorders highlights the importance of the otolaryngologist in patient care at the time of diagnosis. At older ages, a high index of suspicion, adequate tissue biopsy, morphologic evaluation, and immunophenotyping are necessary for accurate and timely diagnosis. The multidisciplinary cooperation between otorhinolaryngologists, hematologists, and anatomic pathologists promote early diagnosis, staging, and treatment.