Case reports
Lymphomas of the head and neck in dermatological practice

Introduction

Neoplasms originating from lymphoid tissues comprise a diverse group of diseases, including Hodgkin’s lymphoma, non-Hodgkin’s lymphoma (NHL), multiple myeloma, and lymphocytic leukemia [1]. The exact etiology of lymphoid neoplasms remains unknown, although a variety of possible risk factors exists including severe immunosuppression caused by various medications as well as some infectious diseases [2-8]. Furthermore, environmental factors including industrialization, certain job specializations, smoking among other life style factors were also suspected to play a role in the pathogenesis of these lymphomas, although they are not fully confirmed [9-15].

Malignant lymphomas of the oral cavity are quite uncommon and account for 3.5% of all oral malignancies. The most common origin of these lesions is in the soft tissues, followed by the bones. Approximately 90% of the malignant lymphomas are B-cell lymphomas, especially diffuse large B-cell lymphomas (DLBCL) [16]. Furthermore, other subtypes of lymphomas may be found in the head and neck area including other types of B-cell lymphomas, T-cell lymphomas [17-20] or NK/T-cell lymphomas (thought before to be the main type affecting the nasal cavity) [21].

The symptoms of lymphomas of the head and neck are commonly atypical and create various diagnostic difficulties. The aim of the study is to present problems encountered during the course of diagnosis of five patients with lymphomas of the head and neck who were consulted also by dermatologists.

Case reports

We present 5 cases of lymphomas of the head and neck with an emphasis on the diagnostic difficulties encountered during the treatment of these patients:

2 females (34- and 39-year-old) with a B-cell lymphoma, a 23-year-old male as well as a 16-year-old female with a T-cell lymphoma, and finally a 49-year-old female with an extranodal NK/T-cell lymphoma, nasal type. All patients were hospitalized at the Department of the Head and Neck Surgery of the Medical University of Gdansk. Hematoxylin-eosin (HE) staining of mucosa and immunohistochemistry of skin biopsy specimens with antibodies against CD2, CD3, CD4, CD5, CD8, CD19, CD20, CD45RO, and CD56 were performed. The patients’ records were then analyzed for the course of the disorder and methods of the treatment.



Case 1



A 34-year-old white female presented with a 2-year history of lesions initially recognized as acute periostitis with unknown etiology. The patient had additionally complained of fever, lack of appetite, weight loss, and night sweats. Hyperthyroidism was ruled out as a differential diagnosis. A radiograph of the oral cavity revealed a reduced density of roots of teeth No. 22 and 23, nonetheless, a diagnosis of hypercementosis was given by the histopathologist. The tooth pulp appeared unaffected at that time, however, in approximately 5 months, necrosis of the pulp of tooth No. 23 as well as a lesion resembling a periosteal abscess was found. The following biopsy confirmed the presence of ostitis. The inflammatory infiltration of the mucosal surface of both maxillary sinuses was also observed in computed tomography (CT). The third histopathological biopsy performed after many consultations revealed a diffuse large B-cell lymphoma. A lymphadenopathy of submandibular lymph nodes was noted, while the chest and abdomen CT appeared unremarkable. The patient was treated with a standard protocol of chemotherapy (CHOP) and radiotherapy with good response. She was lost in

follow up later.



Case 2



A 39-year-old white female presented with a 2-year history of edema of a cheek, with a formation of a small mass that was suspected to have benign inflammatory origin. The clinical picture suggested inflammation of the buccal lymph nodes or odontogenic inflammation. Due to the small size of the lesion, a total diagnostic ex­cision was performed. The histopathological examina­­-

tion revealed a low-grade B-cell lymphoma. Six cycles of chemotherapy (CHOP) were introduced with a good therapeutic effect. The patient has been in remission since the completion of the treatment.



Case 3



A 23-year-old white male presented with a 3-month history of a painless deformation of the left maxilla

(Figure 1). The patient denied any pain or tenderness of the lesion at the time of the initial office visit. A red-blue colored tumor began forming and enlarging progressively following removal of teeth No. 25 and 26, eventually extending from the suborbital to infranasal area. The oral mucosa was noted to be intact in the beginning (Figure 2). The CT revealed a tumor in the left maxillary sinus with destruction of the alveolar processes and infiltration of the ethmoid sinus, left orbital cavity, nasal cavity, and subtemporal fossa (Figure 3). The dermatological consultation suggested later in a biopsy the diagnosis of a high-grade diffuse T-cell lymphoma. The left submandibular, axillary, and inguinal lymph nodes were noted to be enlarged during the clinical examination. There were no signs of neoplastic infiltration in the chest and abdomen. In spite of achieved remission with CHOP chemotherapy and radiotherapy (Figure 4), the patient died 10 months later due to the progression of the

disease.



Case 4



A 49-year-old white female presented to the clinic with a 3-week history of a painful and inflamed right maxillary process, but in good general condition. The dentist diagnosed the patient with chronic periodontitis, extracted teeth No. 14 and 15, and ordered treatment with clindamycin. However the treatment was unsuccessful and the patient’s condition continued to deteriorate. Upon close examination of the oral cavity, inflamed oral mucosa and gross swelling of maxillary alveolar processes were noted. In addition to complaining about paresthesias of the right side of the face supplied by maxillary branch of the trigeminal nerve, the patient also developed annular inflammatory erythematous plaques on the trunk and extremities. During the dermatological consultation, the skin lesions were recognized first to be an allergic reaction to the infection or the drug. On the CT scan, radio-opacity of most of the right maxillary sinus, right nasal cavity, and posterior part of the right pharynx was observed (Figure 5). Subsequent biopsies of the mucosa of the oral cavity only showed nonspecific widespread necrosis and inflammation. On gross examination, granulation tissue was noted on the palate, with necrosis of oral mucosa, palatine tonsil, and of pharyngeal and palatal arches (Figure 6). The third and final histopathological biopsy, performed also after the dermatological consultation, revealed an extranodal NK/T-cell lymphoma, nasal type. Despite maximal efforts to save the patient, she developed progression of the disease, circulatory failure and kidney insufficiency and died 6 weeks after initial office presentation.



Case 5



A 16-year-old white female was hospitalized due to a painful tumor of the left maxillary alveolar process causing facial asymmetry (Figure 7). The patient had been treated for chronic maxillary sinusitis for the previous two years. Despite removal of the tooth 4 weeks prior to hospitalization, progressive growth of the tumor continued to be seen. A hemorrhagic tumor was located on the alveolar process surrounding teeth 3-7 (Figure 8). On careful examination of the lymph nodes, left supraclavicular

(6 cm) and right submandibular (up to 4 cm) lymph nodes were noted to be enlarged. The CT revealed a tumor of this region (Figure 9), while the biopsy revealed an anaplastic ALK(–) CD30(+) T-cell lymphoma. A complete remission was achieved after chemotherapy, however, the patient was lost during follow up.

Discussion

An epidemic of non-Hodgkin’s lymphoma but not other hematopoietic neoplasms has been well documented in many populations [22, 23] with an estimated 50% increase in age-adjusted incidence for the recent few decades of the twentieth century [23-25]. Changes in the diagnostic practice over time and the emergence of acquired immunodeficiency syndrome (AIDS) pandemic in the early 1980s contributed to the rise of NHL but are not sufficient to explain the dramatic increase in incidence of the lymphomas. The use of immunosuppression including corticosteroids, immunomodulators, and che­motherapy in organ transplant recipients, in connective tissue disorders, but also in the less severe dermatologic diseases like psoriasis or atopic dermatitis, has also influenced the steep rise in incidence of these lymphoproliferative disorders [24, 26-30]. Recent reports suggest that the rise in incidence may have slowed in the late 1990s. Interpretation of NHL rates as a single disease entity requires caution, as the rates reflect a combination of diagnostic and etiologic factors that may differ by each disease subtype [26, 31-33].

Lymphomas arising outside the major lymphoid-bearing sites are termed extranodal (including skin derived subtypes). According to this description, Waldeyer’s ring is considered as nodal, but the gastrointestinal tract or upper aerodigestive tract are known as extranodal sites. Primary lymphomas of the upper aerodigestive tract occur most often in the Waldeyer’s ring (pharyngeal tonsil, the paired palatine tonsils, lingual tonsils, and tubal tonsils). There is no well-organized mass of lymphoid tissue in the nasal mucosa, but, in chronic sinusitis, well-developed lymphoid follicles can be formed [34].

The head and neck region is one of the most common sites of extranodal NHL with the Waldeyer’s ring being the most frequent localization [35-37]. Primary lymphomas arising in the oral cavity are rare and represent less than 10% of cases of lymphomas of the head and neck [38]. The palate appears to be the most frequent localization compared to the maxilla, mandible, gum, oral vestibule and mucosal lip [39, 40]. The tumors arise most frequently in the soft tissues and mucosa, and less often in the bone [41]. Primary lymphomas of the nasal cavity and paranasal sinuses are also uncommon and account for 8-16% of the head and neck lymphomas in the Caucasian population [42, 43]. The maxillary sinus is the most frequently involved structure [44]. It may be clinically impossible to distinguish the origin of the tumor based on the localization of first symptoms. The initial signs and symptoms in all of our patients appeared within the oral cavity, despite the primary tumor being located in the maxilla in few of the cases.

Widespread necrosis and inflammation in the region of the head and neck may frequently be dismissed as a benign or infectious inflammatory process. Thus, by the time a biopsy is taken, the lymphoma may already be in an advanced, incurable stage. A correct and timely diagnosis requires an experienced group of collaborating doctors, including surgeons, dermatologists, laryngologists, internists, and hematologists. Performing numerous biopsies with sufficient amounts of tissue is critical to correctly diagnosing a lymphoma of the head and neck. Pathology laboratories are also obligatory; they should have proper equipment that allows accurate immunocytochemistry of tissues, peripheral blood, and bone marrow. Affected patients will generally present with benign inflammatory changes including rhinitis and chronic periodontitis refractory to antibiotic use. Patients may also present with Wegener’s granulomatosis diagnosis itself. The difficulty in the diagnostic process leads to a presentation of an advanced stage of the lymphoma, which then predicts poor prognosis for the patient. As the nature of the disease is one of progressive tissue necrosis, multiple large biopsy specimens are required before sufficient tissue with scattered malignant cells is discovered [45-50]. Careful immunohistochemical assessment is thus vital in order to differentiate these lymphomas from other malignancies as well as benign inflammatory processes.

Most of lymphomas of the head and neck are aggressive B-cell lymphomas like DLBCL (77% of perinasal lymphomas and up to 90% in the oral cavity), followed by indolent lymphomas (MALT type and follicular lymphomas). Burkitt’s and Mantle cell lymphomas are rare and account for 5% [43]. In Asian countries, nasal and PNSL lymphomas are more frequent and most of them have NK/T-cell histology [44]. In our case study, there were two B-cell lymphomas and three T-cell lymphomas, including one extranodal NK/T-cell lymphoma, nasal type, which is extremely rare in the European population.

Extranodal lymphomas arising in the head and neck region typically present with non- specific signs and symptoms. The symptoms depend on the aggressiveness of the disease. In indolent lymphomas obstructive symptoms predominate, whereas in aggressive lymphomas, facial swelling, non-healing ulceration, and bone destruction are more prominent [50-53]. Constitutional symptoms are quite uncommon in the initial stages of lymphomas of the head and neck, as was demonstrated by the cases we presented. The lack of constitutional symptoms is one of the reasons why all of these patients were treated initially as having local inflammatory diseases, which is the most frequent pathology seen in this region.

Differential diagnosis of lymphomas of the head and neck includes odontogenic inflammatory processes, periodontal diseases, other malignancies, as well as other benign inflammatory diseases like nonspecific sinusitis, rhinitis, or even Wegener’s granulomatosis like our 49-year-old patient with the extranodal NK/T-cell lymphoma, nasal type. The lymphomas may not be recognized earlier due to inadequate tissue obtained for biopsy or insufficient information given to the pathologist by the clinician. Ambiguous results of histopathological tests should signal an alert to the physician of a potential presence of a lymphoma. A study by Yen et al. also acknowledged the difficulties in diagnosing sinonasal lymphomas. They pointed out that the presenting symptoms of lymphomas of the head and neck are very similar to benign inflammatory diseases including rhinosinusitis refractory to antibiotic therapy. This group of scientists emphasized the importance of repetitive biopsies containing sufficient amounts of tissue for histopathological identification. Based on their study, a simple punch biopsy in the nasal cavity did not yield a satisfactory amount of tissue in the majority of the patients. More specifically, advanced surgical techniques were often needed to extract an adequate amount of deep tissue, including partial turbinectomy, Caldwell-Luc, and endoscopic sinus surgery techniques. The fact that sinonasal lymphomas coexist with secondary sinusitis and tend to destroy adjacent anatomic structures, is one of the reasons that contribute to difficulty in harvesting an adequate amount of tissue for biopsy. The study emphasized that clinicians need to be aware that superficial biopsies will often not be enough, as the sinonasal lymphomas frequently have much deeper locations. Patients wait an average of 8.9 months to seek medical help after becoming aware of their symptoms. This late presentation in the office contributes to the advanced stage of lymphoma and thus associated poor prognosis [49].

In spite of the detailed characteristics of the classification of lymphomas updated in 2008 by the Worth Health Organization [21], their diagnosis continues to be challenging, as has been demonstrated by previously outlined cases. Clinicians thus need to have a high index of suspicion of these lymphoproliferative disorders during diagnosis of what may initially appear to be a benign inflammatory process. Extranodal NK/T-cell lymphomas, nasal type, are more often found in the nasal cavities and paranasal sinuses, while the B-cell lymphomas occur more frequently in the palatine tonsils and oral cavity. NHL of the oral or nasal cavity does not have characteristic clinical or radiological symptoms. About half of all NHL cases involve the lymph nodes, yet hematogenous dissemination is also observed. Nasal lymphomas can cause nasal obstruction, rhinorrhea or epistaxis. The ulcerating lesions can cause disfigurement, as the nasal bones are eroded [54]. The first symptoms of the disorder in the oral cavity usually suggest inflammatory disease, for example odontogenic inflammation of maxillary bones, sinusitis or non-lymphoproliferative tumors, such as carci­nomas or sarcomas. The erosion of the mucosa on the border of dental prosthesis can also trigger the neoplastic process. Lymphomas are often not painful during the early stages, which often tends to delay their diagnosis. The misdiagnosis may also be caused by inappropriate skin biopsy preservation or by insufficient clinical information presented to the pathologist by the clinician.

The anamnesis and concomitant symptoms should be described in detail. The tissue should be preserved in buffered formalin or sent to the pathologist preserved immediately after the biopsy, which is crucial for performing proper immunohistochemical staining and establishing the correct diagnosis. It is important to recognize the type of lymphoma to choose the appropriate treatment and establish the prognosis. It is very important to differentiate primary lymphomas arising in the oral or nasal cavity from metastasis of other neoplasms to the head and neck region. The prognosis in both cases can be particularly different. Sometimes the process diagnosed initially as a benign inflammation may progress rapidly, and the patient may experience fever, weight loss, and night sweats. And still it is often difficult to recognize the neoplastic process at this stage, especially if the patient was being treated for the past several months for a benign disease. The treatment is often unsuccessful at these late stages, in spite of introducing radiotherapy or chemotherapy. The 5-year survival rate for lymphomas of the head and neck was previously established as 75%, however, it is now known that their recurrence rate is close to 40% [55, 56]. Large cell transformation is clinically significant in some cases of MALT lymphomas and should be documented in histopathological examination. Most importantly, the histopathological subtype of lymphomas has to be correctly established, as it frequently determines the choice of the therapeutic method [57].

In conclusion, the aim of our study was to present the diagnostic difficulties encountered during the diagnosis of lymphomas of the head and neck in dermatological practice. These malignancies often mimic benign inflammatory processes, such as refractory sinusitis or periodontitis, lead to deformities of the face and mucosal lesions, which forces dermatologists to extend the diagnostic process. An accurate diagnosis is often made too late in the disease process, when aggressive chemotherapy and radiotherapy may not be enough to save these patients. Adequate consultations, including dermatological one, and repeated deep tissue biopsies (not punch-biopsies) are often required for a definitive diagnosis, and so is proper tissue biopsy preservation, and thorough clinical information presented to the pathologist by the clinician. Only this will allow for early diagnosis and a potential of saving the life of the patient.

References

 1. Jemal A, Murray T, Warde E, et al. Cancer statistics. CA Cancer J Clin 2005; 55: 10-30.

 2. Fisher SG, Fisher RI. The epidemiology of non- Hodgkin’s lymphoma. Oncogene 2004; 23: 6524-34.

 3. Cartwright RA, Watkins G. Epidemiology of Hodgkin’s disease: a review. Hematol Oncol 2004; 22: 11-26.

 4. Mitsiades CS, Mitsiades N, Munshi NC, et al. Focus on multiple myeloma. Cancer Cell 2004; 6: 439-44.

 5. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804-15.

 6. Linet MS, Devesa SS, Morgan GJ. New perspectives on the epidemiology of hematologic malignancies and related disorders. In: Cancer risk assessment methodologies, biomarkers, and epidemiology. Shields PG (ed.). Marcel Dekker, New York 2005; 647-91.

 7. Hartge P, Bracci PM, Wang SS, et al. Non-Hodgkin lymphoma. In: Cancer epidemiology and prevention. 3rd ed. Schottenfeld D, Fraumeni JF Jr (eds). Oxford Press, Oxford, 2005.

 8. Muller AM, Ihorst G, Mertelsmann R, et al. Epidemiology of non-Hodgkin’s lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol 2005; 84: 1-12.

 9. Barcos M. Mycosis fungoides diagnosis and pathogenesis. Am J Clin Pathol 1993; 99: 452-8.

10. Mouly F, Baccard M, Cayuela JM, et al. Cutaneous T-cell lymphoma associated with granulomatous slack skin. Dermatology 1996; 192: 288-90.

11. Toro JR, Sroll HL, Stomper PC, et al. Prognostic factors and evaluation of mycosis fungoides and Sezary syndrome. J Am Acad Dermatol 1997; 37: 58-67.

12. Romundstad P, Janszky I, Vatten L, et al. Cancer risk factors in PONS. Cancer risk factors in Poland: the PONS Study. Ann Agric Environ Med 2011; 18: 251-4.

13. Zatoński WA; the HEM project team. Epidemiological analysis of health situation development in Europe and its causes until 1990. Ann Agric Environ Med 2011; 18: 194-202.

14. Przewoźniak K, Łobaszewski J, Cedzyńska M, et al. Cigarette smoking among a sample of PONS study subjects: preliminary assessment. Ann Agric Environ Med 2011; 18: 215-20.

15. Stankiewicz-Choroszucha BL, Wawrzyniak ZM, Lipiec A, et al. Consequences of smoke inhalation in the ‘Epidemiology of Allergic Diseases in Poland’ project (ECAP). Ann Agric Environ Med 2011; 18: 420-8.

16. Epstein JB, Epstein JD, Le ND, Gorsky M. Characterization of oral and perioral malignant lymphoma: a population-based review of 361 cases. Oral SurgOral Med Oral Pathol Oral Radiol Endod 2001; 92: 519-25.

17. Felbaum CHR, Hansman ML, Lennert K. Malignant lymphomas of the nasal cavity and paranasal sinuses. Virchow’s Arch A Patho Anat 1989; 414: 399-405.

18. Liang R, Todd D, Chan TK, et al. Treatment outcome and prognostic factors for primary nasal lymphoma. J Clin Oncol 1995; 13: 666-70.

19. Yu KH, Yu SC, Teo PM, et al. Nasal lymphoma resilts of lical radiotherapy wih or without chemotherapy Head Neck 1997; 19: 251-9.

20. Suzumija J, Ohshima K, Tekeshita M, et al. Nasal lymphomas in Japan: a high prevalence of Epstein-Barr virus type A and deletion within the latent membrane proteins gene. Leuk Lymphoma 1999; 35: 567-78.

21. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of the haematopoietic and lymphoid tissues. International Agency of Research on Cancer (IARC), Lyon 2008.

22. Dorn H, Cutler S. Morbidity from cancer in the United States. Public Health Monograph No. 56. Washington DC, US Government Printing Office 1958.

23. Zheng T, Mayne S, Boyle P, et al. Epidemiology of non-Hodgkin’s lymphomas in Connecticut, 1935-1988. Cancer 1992; 70: 840-9.

24. Hartge P, Devesa SS, Fraumeni JF. Hodgkin’s and non-Hodgkin’s lymphomas. Cancer Surv 1994; 19-20: 423-53.

25. Cartwright RA. Time trends in incidence of haematological malignancies and related conditions. Br J Haematol 1999; 106: 281-95.

26. Eltom MA, Jemal A, Mbulaiteye SM, et al. Trends in Kaposi’s sarcoma and non-Hodgkin’s lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst 2002; 94: 1204-10.

27. Hartge P, Devessa SS. Quantification of the impact of known risk factors on time trends in non- Hodgkin’s lymphoma incidence. Cancer Res 1992; 52 (19 Suppl): 5566-9.

28. Devesa SS, Fears T. Non-Hodgkin’s lymphoma time trends: United States and international data. Cancer Res 1992; 52 (19 Suppl): 5432-40.

29. Liu S, Semenciw R, Mao Y. Increasing incidence of non-Hodgkin’s lymphoma in Canada, 1970-1996: age-period-cohort analysis. Hematol Oncol 2003; 21: 57-66.

30. Gail MH, Pluda JM, Rabkin CS, et al. Projections of the incidence of non-Hodgkin’s lymphoma related to acquired immunodeficiency syndrome. J Natl Cancer Inst 1991; 83: 695-701.

31. Clarke CA, Glaser SL. Changing incidence of non-Hodgkin lymphomas in the United States. Cancer 2001; 94: 2015-23.

32. Howe HL, Wingo PA, Thun MJ, et al. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 2001; 93: 824-42.

33. Hardell L, Eriksson M. Is the decline of the increasing incidence of non-Hodgkin lymphoma in Sweden and other countries a result of cancer preventive measures? Environ Health Perspect 2003; 111: 1704-6.

34. Lucas HA. The histopathology of sinusitis. J Laryngol Otol 1952; 66: 480-9.

35. Otter R, Gerrits WB, Sandt MM, et al. Primary extranodal and non-Hodgkin’s lymphoma. A survery of a population-based registry. Eur J Cancer Clin Oncol 1989; 25: 1203-10.

36. Shima N, Kobashi Y, Tsutsui K, et al. Extranodal non-Hodgkin’s lymphoma of the head and neck. A clinicopathologic study in the Kyoto-Nara area of Japan. Cancer 1990; 66:

1190-7.

37. Lopez-Guillermo A, Colomo L, Jimenez M, et al. Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. J Clin Oncol 2005; 23: 2797-804.

38. Kolokotronis A, Konstantinou N, Christakis I, et al. Localized B-cell non-Hodgkin’s lymphoma of oral cavity and maxillofacial region: a clinical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 99: 303-10.

39. Leong IT, Fernandes BJ, Mock D. Epstein-Barr virus detection in non-Hodgkin’s lymphoma of the oral cavity: an immunocytochemical and in situ hybridization study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 92: 184-93.

40. Rinaggio J, Aguirre A, Zeid M, Hatton MN. Swelling of the nasolabial area. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 89: 669-73.

41. Van der Waal RI, Huijgens PC, van der Valk P, van der Waal I. Characteristics of 40 primary extranodal non-Hodgkin lymphomas of the oral cavity in perspective of the new WHO classification and the International Prognostic Index.

Int J Oral Maxillofac Surg 2005; 34: 391-5.

42. Jacobs C, Weiss L, Hoppe RT. The management of extranodal head and neck lymphomas. Arch Otolaryngol Head Neck Surg 1986; 112: 654-8.

43. Cortelazzo S, Rossi A, Federico M, et al. The stage modified IBI (MIPI), histology, and combined treatment influence the clinical outcome of 401 patients with primary extranodal head and neck lymphomas (PHNBCL). Blood 2005; 106: Abstract 927.

44. Jaffe ES, Chan J, Su IJ, et al. Report of the workshop on nasal and related extranodal angiocentric T/natural killer cell lymphomas: definitions, differential diagnosis, and epidemiology. Am J Surg Pathol 1996; 20: 103-11.

45. Khariwala S, Litman D, McQuone S, et al. Quiz case 2: diagnosis natural killer (NK) cell/peripheral T-cell lymphoma. Arch Otolaryngol Head Neck Surg 2000; 126: 1391-3.

46. Chor-Sang C, Shing-Yan M, Wing-Yan A, et al. Primary nasal natural killer cell lymphoma: long-term outcome and relationship with the International Prognostic Index. Neoplasia 2004; 103: 216-21.

47. Sheahan P, Donnelly M, O’Reilly S, Murphy M. Pathology in focus: T/NK cell non-Hodgkin’s lymphoma of the sinonasal tract. J Laryngol Otol 2001; 115: 1032-5.

48. Davidson S, Habermann T, Strickler J, et al. Nasal and nasopharyngeal angiocentric T-cell lymphomas. Laryngoscope 1996; 106: 139-43.

49. Yen TT, Wang RC, Jiang RS, et al. The diagnosis of sinonasal lymphoma: a challenge for rhinologists. Eur Arch Otorhinolaryngol 2012; 269: 1463-9.

50. Sokołowska-Wojdyło M, Sikorska M, Roszkiewicz J. Diagnostic and therapeutic difficulties in nasal-type NK/T-cell lymphoma – a case report. Postep Derm Alergol 2011; 28: 59-62.

51. Neves MC, Lessa MM, Voegels RL, Butugan O. Primary non-Hodgkin’s lymphoma of the frontal sinus: case report and review of the literature. Ear Nose Throat J 2005; 84: 47-51.

52. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of tumours of the hematopoietic and lymphoid tissues. International Agency of Research on Cancer (IARC), Lyon 2008.

53. Abbondanzo SL, Wenig BM. Non-Hodgkin’s lymphoma of the sinonasal tract. A clinicopathologic and immunophenotypic study of 120 cases. Cancer 1995; 75: 1281-91.

54. Fernandes SV. Hen’s teeth? Extranodal marginal zone B cell lymphoma of MALT type in nasal mucosa. ANZ J Surg 2004; 74: 1127-8.

55. Thieblemont C, Bastion Y, Berger F, et al. Mucosa associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behaviour: analysis of 108 patients. J Clin Oncol 1997; 15: 1624-30.

56. Morinaka S, Ichimaya M, Nakamura H. Detection of Helicobacter pylori in nasal and maxillary sinus specimens form patients with chronic sinusitis. Laryngoscope 2003; 113:

1557-63.

57. Isaacson PG. Review. The current status of lymphoma classification. Br J Dermatol 2000; 109: 258-66.