Hodgkin Lymphoma presenting as persistent sore throat.

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Caso Clínico

Odinofagia persistente como manifestação

primária de Linfoma de Hodgkin

Hodgkin Lymphoma presenting

as persistent sore throat.

Joana Silva

1

, Isabel Pinto

1

, José Peneda

1

,

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ISSN:

2340-3438

Edita:

Sociedad Gallega de Otorrinolaringología

Porto, Portugal

Corresponding Author: Joana Silva

Department of Otolaryngology,

Centro Hospitalar Vila Nova de Gaia/Espinho,

Porto, Portugal

Rua Conceição Fernandes 1282

4434-502 Vila Nova de Gaia, Porto, Portugal

Tel: +351 912443623

E-mail: joanavilela.silva@gmail.com

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Acta Otorrinolaringol. Gallega 2019; 12: 67-76

Resumen

As amígdalas palatinas podem ser afetadas por diversas patologias, incluindo doenças inflamatórias, infeciosas e neoplásicas. Apesar dos linfomas serem a segunda neoplasia maligna mais comum da cabeça e pescoço, o linfoma de Hodgkin extranodal é raro.

As manifestações mais comuns de doença de Hodgkin incluem o aparecimento de linfadenopatias e sintomas constitucionais. Os autores apresentam o caso raro de um linfoma de Hodgkin que se manifestou primariamente como uma massa amigdalina. Neste trabalho enfatizamos a importância do aspecto macroscópico das lesões amigdalinas que poderão ser importantes na suspeição de doença linfoproliferativa.

Palabras chave

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Abstract

Several clinical conditions may affect the palatine tonsil, including inflammatory, infectious and tumoral diseases. Despite lymphomas are the second most common malignancy of the head and neck, extranodal Hodgkin lymphoma is a rare occurrence.

The most common manifestations of Hodgkin disease include enlarged lymph nodes and constitutional symptoms. We present the rare case of Hodgkin lymphoma presenting with a tonsillar mass. We emphasize the importance of the macroscopic appearance of tonsillar lesions that may yield the key to anticipate the diagnosis of this condition.

Keywords

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Introduction

A considerable amount of pathological conditions may affect the palatine tonsil, including inflammatory, infectious and tumoral diseases. Lymphomas constitute a heterogeneous group of lymphoproliferative disorders that arise from the cells of the immune system, and are the second most frequent head and neck malignancy, after squamous carcinoma.(1,2_{) They are broadly categorized into the most common}

non-Hodgkin lymphoma and the rarer non-Hodgkin disease (HD).

The term extranodal lymphoma has been applied in cases where neoplastic proliferation occurs at locations other than the lymph nodes, sometimes from sites that normally do not contain lymphoid tissue. (3,4_{) This presentation can be seen in up to one-third of non-Hodgkin lymphomas but is rare in HD.(}5₎

Waldeyer ring is an extranodal site that encompasses the lymphoid tissue of the palatine tonsils, the base of tongue, nasopharynx and oropharynx.(6_{) In these cases, the gastrointestinal tract is the most frequently}

reported extranodal site. However, head and neck extranodal lymphomas may affect the sinonasal tract, nasopharynx, tonsil, parotid gland, orbit and other even rarer locations.(7,8₎

The most frequent symptoms of HD at presentation include cervical lymph node enlargement and constitutional symptoms. Initial presentation with sore throat complaints is rare and may present a diagnostic challenge.(7,9₎

Case Report

A 69-year-old patient was referred to our department with a sore throat of two months duration that was progressively becoming more severe. Despite slight weight loss that the patient perceived to be associated with uncontrolled pain, he presented no other symptoms. His past medical history included controlled hypertension and type 2 diabetes mellitus, ischemic heart disease and ulcerative colitis medicated with azathioprine and mesalazine. He was a former smoker, without smoking habits over the past sixteen years.

He had been seen at another facility, where he was initially medicated with a seven-day course of amoxicillin-clavulanic acid, without improvement. He brought the results of a previously performed cervical computed tomography (CT) scan and a biopsy specimen. The former showed a right tonsillar mass with 3.5 X 2.4 cm, infiltrating the lateral pharyngeal wall and several enlarged lymph nodes, the larger with 2.6 X 1.6 cm with a necrotic core. The histology of the mass showed neutrophilic tonsillar infiltration suggestive of an acute suppurative condition.

Physical examination revealed an enlarged right tonsil covered with a white exudate (Figure 1.). Epithelial alignment looked friable and there was a sharp transition to normal mucosa near the palatoglossal and palatopharyngeal arcs. We also noticed an enlarged, consistent and painless jugular lymph node, with approximately 2cm on the right side. There were no other significant findings on physical examination.

Figure 1: right tonsilar mass (1); uvula (2); soft palate (3); tongue (4). The lesion presented as tonsillar

hypertro-phy with ulcerative epithelia covered in a white exsudate. Note the sharp

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Full blood count revealed a normocytic normochromic anemia of 12.4g/dl, biochemical tests, and serum lactate-dehydrogenase were normal, and erythrocyte sedimentation rate was 93 mm in the first hour. Human immunodeficiency virus type 1 and 2 and hepatitis B and C were negative.

Microbiological and mycobacterial tests were also

negative. Repeated biopsy of the mass showed granulomas with polymorphonuclear infiltrate and rare cells Reed-Sternberg like. These cells were positive for CD30, CD15, and EBER and showed week positivity to CD20 and Pax 5.

Cervical lymph node excisional biopsy was performed in order to confirm the diagnosis and determine the disease subtype, and concluded to a nodular sclerosis variant Hodgkin lymphoma (Figure 2.). Tumor cells were positive for CD30 and CD15 and negative for CD45, CD3, and EMA. Few cells were positive for CD20

and Pax 5. EBER was detected in the tissue sample by in situ hybridization.

Computerized axial tomographic scan of chest, abdomen, and pelvis, positron emission tomography and bone marrow biopsy allowed the disease to be staged as IIB.(10₎

Figure 2. Hodgkin lymphoma afflicting the tonsillar tissue and cervical lymph nodes. A) Nodular sclerosis variant Hodgkin lym-phoma involving cervical lymph nodes (hematoxilin-eosin, 100x). B) Detailed binucleated Reed-Sternberg cells (hematoxilin-eosin, 200x). C) CD30 immunohistochemical staining in Hodgkin cells

evidencing typical membranous and Golgi pattern (200x). D) CD15 immunohistochemical staining (200x). E) EBER

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In this atypical location, secondary involvement is more frequent than a primary tonsillar disease.(7₎

Although a few cases of primary Waldeyer ring Hodgkin lymphoma are described in the literature, many studies did not include immunohistochemical workup.(6_{) Indeed, NHL may be mistaken by HD and a full}

workup is necessary to allow an accurate classification of lymphoproliferative disorders.(6,8₎

The variant most frequently described in this setting is mixed cellularity, although in one study lymphocyte-rich and nodular sclerosis types of HD were more frequent.(6₎

When HD presents with oropharynx and cervical lymph node involvement, as in our case, it may be difficult to determine the primary site of origin.(7_{) Primary nodal disease with secondary tonsil involvement}

is more frequent in Hodgkin disease. However, several factors, in this case, may be consistent with an extranodal presentation. First, the only symptom reported was a sore throat, which was present for at least two months, while the cervical lymph node was only noted on physical examination. Second, clinical evolution favored a tonsillar origin. Though cervical lymph nodes remained stable throughout vigilance until treatment was started, the tonsillar mass presented several changes. Initially, it enlarged and later regressed, with visible necrosis, exposing the tonsillar bed, which was suggestive of an intense proliferative focus.

Immunodeficiency and EBV are possible explanations for Waldeyer ring involvement in HD.(6_{) Waldeyer}

lymphoid tissue is a known reservoir of EBV and due to its oncogenic potential, some authors propose it as a possible explanation for Waldeyer ring lymphomas.(6, 7, 11₎

One study showed that EBV latent membrane protein expression by Reed Sternberg cells was more frequent in neck nodes compared with other site nodes, reflecting oropharynx drainage pathways.(11₎

The diagnosis of lymphoproliferative disorders presenting as tonsillar masses is not always straightforward. Not infrequently, several biopsy specimens are necessary before the diagnosis is highlighted.(3,4₎

Immunohistochemical studies and flow cytometry are needed to establish a definitive diagnosis and analysis of a representative amount of fresh tissue is necessary to examine the architecture of the proliferative lesion.(8₎

Although constitutional symptoms are more frequent among HD patients, in most cases these are absent. Also, lymph node enlargement may be absent or indistinguishable from other types of malignancy or non-malignant disorders, which may further delay the diagnosis.(4_{) Although fine needle biopsy can usually}

differentiate between a carcinoma and a lymphoma, a high index of suspicion is necessary to provide sufficient amount of tissue to allow a complete and prompt diagnostic workup of the later.(8_{) Factors that}

may be helpful include patients’ age and habits, immune status and inconclusive previous biopsies.(2,8,9_{) In}

our experience, the presence of a well-demarked mass with a sharp transition to normal mucosa, along with lymphoid hypertrophy is suggestive of a lymphoma, when a neoplastic cause is suspected. Constitutional symptoms and lymph node enlargement are inconsistent features among HD patients and, when present, may be indistinguishable from those associated with other malignant and non-malignant conditions. Table 1 summarizes the main findings of Waldeyer ring Hodgkin lymphomas in previous studies.

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Table 1. Resume of the main findings in Waldeyer ring Hodgkin lymphomas( ). Report Patients’ characteris-tics Symtoms/ Clinical Findings Histology Location Quiñones- Avila et al. (n=22)

Male prepon-derance,

median age of 48 years, history of NHL in 14%.

Tonsil

enlargement in 18%

Lymph node en-largement in 14%

lymphocyte-rich classical (36%),

nodular sclerosis (32%), mixed

cellularity (18%), lymphocyte depletion (5%).

Localized to

Waldeyer ring in 32%.

Waldeyer ring and cervical lymph nodes in 50%.

Qin Y et al. Male, 43 years.

Night sweats, tonsillar

asymmetry, cervi-cal lymph nodes enlargement

Lymphocyte-rich classical (misdiagnosed as

lymphoepithelial carcinoma).

Tonsil, cervical lymph nodes. Prudhom-me-Lacroix F et al. (n=3) Male, >40 years.

Mixed cellularity. Tonsil.

Chang KL et al.

Variable. Tonsil enlargement.

Nodular lymphocyte predominance.

Tonsil +/- cervical lymph nodes. Ioannou MG et al. Male, 43 years. Dysphagia, breathlessness, tonsillar asymmetry. Nodular lymphocyte predominance. Tonsil, cervical lymph nodes. Oluwasanmi AF et al.

Female, 52 years.

Tonsil enlargement.

Lymphocyte-rich classical. Tonsil.

Baden E et al. (n=2) Male, >50 years. Tonsillitis, dysphagia, Nodular sclerosis, mixed cellularity.

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References

1. DePena CA, Van Tassel P, Lee YY. Lymphoma of the head and neck. Radiologic clinics of North America 1990;28:723-743.

2. Rettig EM, D’Souza G. Epidemiology of head and neck cancer. Surgical oncology clinics of North America 2015;24:379-396.

3. Ömür Ö, Baran Y, Oral A, Ceylan Y. Fluorine-18 fluorodeoxyglucose PET-CT for extranodal sta-ging of non-Hodgkin and Hodgkin lymphoma. Diagnostic and interventional radiology (Ankara, Turkey) 2014;20:185-192.

4. Urquhart A, Berg R. Hodgkin’s and non-Hodgkin’s lymphoma of the head and neck. The Laryngos-cope 2001;111:1565-1569.

5. Thakral B, Zhou J, Medeiros LJ. Extranodal hematopoietic neoplasms and mimics in the head and neck: an update. Human pathology 2015;46:1079-1100.

6. Quinones-Avila Mdel P, Gonzalez-Longoria AA, Admirand JH, Medeiros LJ. Hodgkin lymphoma involving Waldeyer ring: a clinicopathologic study of 22 cases. American journal of clinical pathology 2005;123:651-656.

7. Aloulou S, Farhat H, Bosq J, Vanel D, Ribrag V, Turhan AG, et al. Hodgkin’s disease primarily invol-ving the oropharynx: case report and review of the literature. Hematol J 2002;3:164-167.

8. Hanna E, Wanamaker J, Adelstein D, Tubbs R, Lavertu P. Extranodal lymphomas of the head and neck. A 20-year experience. Archives of otolaryngology--head & neck surgery 1997;123:1318-1323.

9. Ansell SM. Hodgkin Lymphoma: Diagnosis and Treatment. Mayo Clinic proceedings 2015;90:1574-1583.

10. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32:3059-3068.

11. O’Grady J, Stewart S, Elton RA, Krajewski AS. Epstein-Barr virus in Hodgkin’s disease and site of origin of tumour. Lancet (London, England) 1994;343:265-266.

12. Prudhomme-Lacroix F, Jaubert J, Mosnier JF, Guyotat D. [Hodgkin disease of the palatine ton-sil. Clinical, histological, immunophenotype study and association with Epstein-Barr virus]. Presse Med 2000;29:935-938.

13. Qin Y, Lu L, Lu Y, Yang K. Hodgkin lymphoma involving the tonsil misdiagnosed as tonsillar carci-noma: A case report and review of the literature. Medicine 2018;97:0000000000009761.

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15. Oluwasanmi AF, Wood SJ, Baldwin DL, Sipaul F. Malignancy in asymmetrical but otherwise normal palatine tonsils. Ear Nose Throat J 2006;85:661-663.

16. Ioannou MG, Kouvaras E, Gletsou E, Papacharalambous C, Matsouka P, Koukoulis GK, et al. No-dular lymphocyte-predominant Hodgkin lymphoma of the tonsil: a case study using immunohistochemistry and FISH analysis and review of the literature. Journal of Hematopathology 2011;4:227-231.

17. Chang KL, Kamel OW, Arber DA, Horyd ID, Weiss LM. Pathologic features of nodular lymphocyte predominance Hodgkin’s disease in extranodal sites. Am J Surg Pathol 1995;19:1313-1324.