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CASE REPORT |
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Year : 2019 | Volume
: 6
| Issue : 1 | Page : 49-53 |
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Extranodal NK/T cell lymphoma: diagnostic challenges in a resource-constrained setting
Murtala Abubakar1, Iliyasu Y Shuaibu2, Dotiro Chitumu2, Almustapha Aliyu Liman1, Dauda E Suleiman1
1 Department of Histopathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria 2 Division of Otorhinolaryngology, Department of Surgery, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
Date of Web Publication | 10-Oct-2019 |
Correspondence Address: Dr. Murtala Abubakar Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria - 810 001, Kaduna State Nigeria
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/ssajm.ssajm_37_18
Introduction: Extranodal natural killer/T-cell lymphoma (NKTCL)- nasal type is a rare form of non-Hodgkin lymphoma. It mainly affects the midfacial structures (the nose, oropharynx, and hypopharynx). Prognosis is generally very poor and diagnosis is often delayed in Africans because of low index of clinical suspicion and resource constraints. Case report: The patient was a 30-year-old man who presented with a 5-month history of rhinorrhea associated with blockage of the left nasal cavity. Examination revealed a fleshy left nasal mass. Incisional biopsy of the mass was reported as nonspecific chronic inflammation but the diagnosis was reviewed to non-Hodgkin lymphoma after histologic examination of the excised mass. Subsequent immunohistochemical studies established a diagnosis of NKTCL 6 months after initial presentation. The patient was placed on chemotherapy and radiotherapy. He did not have access to radiotherapy because of financial constraints and defaulted from care after he has had three cycles of chemotherapy. The patient died 4 months after defaulting. Conclusion: It is very common to miss the diagnosis of the early phase of NKTCL before the appearance of the destructive facial lesion. Low index of suspicion and constraints of resources also play a role in the delayed diagnosis and poor outcome in Africa.
Keywords: Africa, delayed diagnosis, extranodal NK-T cell lymphoma
How to cite this article: Abubakar M, Shuaibu IY, Chitumu D, Liman AA, Suleiman DE. Extranodal NK/T cell lymphoma: diagnostic challenges in a resource-constrained setting. Sub-Saharan Afr J Med 2019;6:49-53 |
How to cite this URL: Abubakar M, Shuaibu IY, Chitumu D, Liman AA, Suleiman DE. Extranodal NK/T cell lymphoma: diagnostic challenges in a resource-constrained setting. Sub-Saharan Afr J Med [serial online] 2019 [cited 2024 Mar 29];6:49-53. Available from: https://www.ssajm.org/text.asp?2019/6/1/49/268790 |
Background | | |
Natural killer/T-cell lymphoma (NKTCL) is a rare form of non-Hodgkin lymphoma (NHL) associated with Epstein-Barr virus (EBV).[1] It is more common in Asia and Central and South America, accounting for up to 20% of NHL cases, whereas in Europe and North America, it constitutes only about 1% of NHL.[2],[3] The prevalence of the disease in sub-Saharan Africa and indeed in Africans, in general, is largely unknown.[4] This relative paucity of local literature has raised questions considering the high prevalence of the associated infectious agent, EBV, in the region,[5] as well as high prevalence of other EBV-related lymphomas like endemic Burkitt and Hodgkin lymphomas.[6] Some authors have attributed the scarcity in documented cases of NKTCL from this region to underreportage of the disease due to the relative nonavailability of the requisite immunohistochemical and molecular diagnostic techniques to allow phenotypic and genotypic characterization of cases as to fully distinguish them from other NHLs.[6] The lesion is seen in both sexes, but is slightly common in males.[3]
Histogenetically, NKTCL most commonly expresses NK cell phenotype, being positive for CD56, cytoplasmic CD3ε+, without surface T-cell receptor (TCR) and TCR gene rearrangements.[7] Some cases, however, have demonstrated a T-cell phenotype with clonal TCR gene rearrangements.[8]
The disease most commonly involves the nasopharynx and nasal cavity; however, it might also affect some other parts of the upper aerodigestive tract.[9],[10] Sites for extranasal involvement include skin, soft tissue, gastrointestinal tract, and testes.[7]
Clinically, NKTCL is characterized by initial nonspecific signs and symptoms that include nasal stuffiness, rhinitis, and epistaxis. The specific feature of rapidly progressive midline facial destruction follows this initial phase. Systemic symptoms such as fever, weight loss, weakness, nocturnal sweating, increased susceptibility to infections, lymphadenopathy, and splenomegaly are frequently reported at this stage of the disease.[11] As the tumor mass enlarges, it invades and destroys structures in the upper aerodigestive tract, becoming progressively necrotic with a purulent discharge. Secondary infection and hemorrhage are common features. Metastasis is, however, uncommon.[12]
High index of suspicion is needed for diagnosis especially because of the nonspecific nature of the initial clinical features. Immunohistochemistry is the gold standard in diagnosis to be supplemented with imaging.[4] Due to the rapid clinical course of the disease, prompt institution of treatment with chemoradiation is highly important along with the recent improvements in prognosis recorded in the treatment of early as compared to late-stage disease.[13]
Case report | | |
The patient was a 30-year-old man referred to the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, from Niamey, Niger Republic, on March 28, 2017, with a 5-month history of rhinorrhea and a 2-month history of progressive blockage of the left nasal cavity. Rhinorrhea was initially of clear fluid with no associated bleeding from the nasal cavity. Nasal blockage was associated with pain and swelling on the left side of the nose. There was no associated numbness on any part of the face and no loosening of any tooth. There was no history of fever or weight loss. No history of any systemic disorder, smoking, drug abuse, or alcohol was found. He worked as a welder.
On physical examination, he was found to be having facial asymmetry with swollen left ala nasi and left-sided deviation of the nasal septum. The left nasal cavity was filled with a fleshy mass extending and attached to the nasal septum. The mass bled on contact. The right nasal cavity along with the right and left ears were essentially normal. Throat examination revealed grade II tonsils with no features of ongoing inflammation. No significant lymphadenopathy was noted in the neck or other regions.
An initial assessment of a left nasal mass to rule out papilloma was made and a biopsy of the mass was submitted for histology. Results of urea/electrolytes/creatinine and full blood count and differentials were essentially normal. Computed tomographic (CT) scan of the head and neck could not be done on account of patient’s financial constraints. He was placed on antibiotics and steam inhalation.
On the first follow-up visit, the histology report of the left nasal mass biopsy showed chronic nonspecific inflammation. The patient was booked for nasal clearance along with left intranasal antrostomy. The procedure was carried out 2 weeks later with intraoperative findings of multiple masses in the left nasal cavity with bleeding on contact. He was discharged on the sixth day postoperation after antral lavage.
Three months after discharge, the patient represented with a rapidly progressive nasal mass with ulcerative changes. CT scan done at this stage revealed destruction of the nasal septum, and the middle and inferior nasal turbinates extending to the vestibule. There was an associated foul smelling discharge and contact bleeding [Figure 1] and [Figure 2]). A repeat biopsy was taken and the patient underwent nasal toileting and dressing. The histology report revealed a NHL but the immunohistochemical studies necessary for further characterization were temporarily unavailable. The patient was referred to the Haematology Clinic where he was placed on chemotherapy using a combination of cyclophosphamide, hydroxyurea, oncovin, and prednisolone (CHOP regimen). There was no significant improvement after three cycles and another tissue was sent for histopathological assessment after a repeat nasal toileting was done. The pathological examination showed an ulcerative and necrotic tumor composed of sheets of atypical small and large lymphocytes having predominantly vesicular nuclei with inconspicuous nucleoli and abundant pale cytoplasm. The lesion exhibited prominent angiocentric and angioinvasive patterns [Figure 3],[Figure 4],[Figure 5]. | Figure 1 Photograph showing ulcerative nasal lesion before commencement of chemotherapy.
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| Figure 2 Photograph showing ulcerative nasal lesion after 3 courses of chemotherapy.
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| Figure 3 Micrograph showing sheets of malignant lymphoid cells. H&E x630.
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| Figure 4 Micrograph showing foci of angiocentricity and angioinvasion by tumor cells.
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Immunohistochemistry showed positivity of tumor cells for CD56 [Figure 6], CD45 [Figure 7], and CD5 [Figure 8]. CD20 and AE1/AE3 stains were negative.
A final diagnosis of extranodal NKTCL was made and the result was communicated to the hematologist who recommended additional chemotherapy and radiotherapy. The patient, however, defaulted from follow-up on account of financial constraints. He was said to have gone back to his native country (Niger Republic) to continue with traditional medications. He died 4 months thereafter. No postmortem examination was conducted.
Discussion | | |
Extranodal NKTCL-nasal type is an aggressive form of NHL that characteristically involves the nasal cavity and, to a lesser extent, other parts of upper aerodigestive tract. The disease is more common in Asia, and South and Central America with very few cases reported in sub-Saharan Africa.[5] This has been attributed to underdiagnosis given the well-documented diagnostic limitations in the region.[6] The theory of underreportage may be supported by the fact that some studies from the region have described NHL of the nasal cavity and nasopharynx but, however, were constrained by the nonavailability of the requisite immunohistochemical and molecular techniques that will enable precise characterization of the lesion as NKTCL.[14],[15]
Our case highlighted the myriad of challenges preventing prompt diagnosis of this tumor as well as those contributing to the overall poor prognosis among our patients, particularly after suboptimal treatment, as obtained in our setting.
Our patient was 30 years of age at the time of presentation. Gregory et al. [16] reported the mean age of presentation as 45 years, with age range of 19 to 80 years. A presentation age of 30 years was reported from a previous report from our environment.[4]
The initial presenting complaints in our patient were rhinorrhea and nasal blockage with the characteristic destruction of the midfacial structures developing over a period of 11 months. Similar nonspecific initial presenting symptoms were previously reported.[4],[12] This, coupled with low index of clinical suspicion, may be contributory to the delayed diagnosis and poor prognosis as suggested by other studies.[13],[18]
Imaging studies such as nasal endoscopy and CT scan play a crucial role in the management of patients with NKTCL.[4] Although there is no agreement as to specific radiological features of the disease, findings of destruction of the nasal septum, nasal turbinate, and extension into paranasal sinuses are commonly reported by various authors.[12],[18] These features help to localize the lesion, monitor the level of progression over a given period of time, and estimate the effectiveness of treatment.[4] Our patient had a CT scan only at a later stage of the disease due to financial constraints at presentation. That may be contributory to the late diagnosis and the poor outcome.
The characteristic morphological features of angiocentric and angiodestructive growth pattern seen in NKTCL may be missing in the early stages of the disease with the predominant features being those of polymorphous cellular infiltrates composed of plasma cells, lymphocytes, macrophages, and eosinophils similar to what is seen in a chronic inflammatory process.[12] In our patient, the initial biopsy was reported by the histopathologist as chronic nonspecific inflammation. The excision biopsy, however, was reported as NHL, but further characterization was not possible because of temporary nonavailability of immunohistochemical studies. Later immunohistochemical studies revealed positivity of the tumor cells to CD56, CD45, and CD5, and negative staining patterns for epithelial cell markers (AE1, AE3) and B cell marker (CD20). CD56 is a marker of NK cell lineage, which is the precursor cells in NKTCL that further strengthened our diagnosis. CD45 and CD5 positivity have also been reported in cases of NKTCL.[12],[18]. Diffuse large B-cell lymphoma is a form of B-cell lymphoma that commonly involves the nasal cavity and the nasopharynx, but the CD20 negativity of the tumor cells in our case served to rule it out.The diagnosis was, however, only made late in the course of the disease, and absence of optimal chemoradiation therapy further contributed to the rapid clinical deterioration and ultimately the death of our patient. Similar reports of overall poor prognosis in patients with NKTCL, especially in the settings of late diagnosis and suboptimal therapy, have been corroborated by several other studies.[6],[12],[17]
Conclusion | | |
NKTCL can present with nonspecific clinical features in the early phase and may mimic many other diseases of the nasal cavity. The histological features may also resemble chronic inflammatory conditions on account of the polymorphous nature of the comprising tumor cells as evidenced by its former name (polymorphous reticulosis). Hence, in resource-constrained settings such as ours, prompt diagnosis, which is the backbone of effective treatment, constitutes a difficult challenge. Multicenter collaborations will help to determine the prevalence of this condition so as to raise the index of suspicion among our clinicians.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References | | |
1. | Li S, Feng X, Li T, Zhang S, Zuo Z, Lin P et al. Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center. Am J Surg Pathol 2013;37:14-23. |
2. | Aozasa K, Zaki MA. Epidemiology and pathogenesis of nasal NK/T-cell lymphoma: a mini-review. Scientific World J 2011;11:422-8. |
3. | William BM, Armitage JO. International analysis of the frequency and outcomes of NK/T-cell lymphomas. Best Pract Res Clin Haematol 2013;26:23-32. |
4. | Bakari A, Iliyasu Y, Kirfi AM. Extranodal NK/T-cell lymphoma in an African. Highland Med Res J 2017;17:62-5. |
5. | Schuler A, Smith E, Lowe L, Helfrich Y, Michigan AA. Extranodal natural killer/T-cell lymphoma, nasal type: a rare but critical diagnosis. J Am Acad Dermatol Case Rep 2017;3:225-7. |
6. | Tomoka T, Powers E, van der Gronde T, Amuquandoh A, Dhungel BM, Kampani C et al. Extranodal natural killer/T cell lymphoma in Malawi: a report of 3 cases. BMC Cancer 2017;17:633. |
7. | Jaffe ES, Harris NL, Stein H, Campo E, Pileri SA, Swerdlow SH. Introduction and overview of the classification of the lymphoid neoplasms. In: Swerdlow SH, Campo E, Harris NL et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. pp. 157-66. |
8. | Liang R. Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal type. Br J Haematol 2009;147:13-21. |
9. | Davorin D, Ana DH, Ivana M. Primary extranodal natural killer/T-cell lymphoma of the ethmoid sinus masquerading as orbital cellulitis. Medicinski Glasnik 2014;6:934-938. |
10. | Termote K, Dierickx D, Verhoef G, Jorissen M, Tousseyn T, Mombaerts I. Series of extranodal natural killer/T-cell lymphoma, nasal type, with periorbital involvement. Orbit 2014;33:245-51. |
11. | Joshi S, Jagade MV, Saurabh A, Dnyaneshwar A, Sunita B. Extranodal natural-killer/T-cell lymphoma, nasal type − presenting as non-healing palatal ulcer. Otolaryngology 2012;2:123. |
12. | Tlholoe MM, Kotu M, Khammissa RAG, Bida M, Lemmer J, Feller L. Extranodal natural killer/T-cell lymphoma, nasal type: ‘midline lethal granuloma.’ A case report. Head Face Med 2013;9:4. |
13. | Lee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol 2006;24:612-8. |
14. | Sabageh D, Solaja TO, Olasode BJ. Malignant tumors of the upper aerodigestive tract as seen in a Nigerian tertiary health institution. Niger J Clin Pract 2015;18:231-5. [ PUBMED] [Full text] |
15. | Onakoya PA, Adeyi OA, Nwaorgu OG, Ojemakinde KO, Thomas JO. Primary extranodal non-Hodgkin’s lymphoma of the upper aerodigestive tract − a descriptive analysis of the pattern seen in the University College Hospital, Ibadan. Afr J Med Med Sci 2003;32:59-63. |
16. | Gregory H, Kathleen M, Maruisz W, Ara C, Richard H. Nasal T-cell lymphoma and the lethal midline granuloma syndrome. Otolaryngol Head Neck Surg 1996;114:653-6. |
17. | Mehta V, Balachandran C, Bhat S, Geetha V, Fernandes D. Nasal NK/T cell lymphoma presenting as a lethal midline granuloma. Indian J Dermatol Venereol Leprol 2008;74:145-7. [ PUBMED] [Full text] |
18. | Ashraf MT, Baba KM, Meenu G, Syed A, Katoch SS, Imran N. Lethal midline granuloma presenting as facial cellulitis. JK Sci 2009;11:39-41. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
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