arge cell lymphoma | The extranodal nasal type NK/T cell lymphoma: tumor primitive, rare and aggressive of the soft palate

The extranodal nasal type NK/T cell lymphoma: tumor primitive, rare and aggressive of the soft palate


Summary
Introduction: The lymphoma T/NK extranodal nasal type, seat at the level of the nasal cavity in 75% of cases. Extranasale primitive location at the level of the soft palate has been exceptionally reported in the literature. Comment: It's an adult 24 years which featured isolated ulceration of the soft palate. This lesion has quickly evolved into a month in a context of significant alteration of the general State towards an inflammatory infiltration extensive and necrotic of the soft palate. Three deep biopsies enabled the extranodal NK/T Lymphoma diagnosis of nasal type. This Lymphoma then invaded the Palatine tonsils, the cavum and parapharynges spaces. Terminal evolution was marked by the occurrence of a pancytopenia with infringement hepatosplenique as part of a syndrome of macrophagique activation that has complicated this pathology polyposis. The patient died by a hepatic encephalopathy just after the first chemotherapy treatment. Conclusion: Extranodal NK/T type primitive to the soft palate, nasal lymphoma is exceptional. This extranasale form is distinguished by its clinical polymorphism, his aggression and his prognosis is dark. This prognosis is further aggravated by the syndrome of macrophagique activation. Its management is multidisciplinary, must be fast and its treatment benefits new chemotherapy Protocol.

English Abstract
Introduction: Extranodal NK/T nasal cell type lymphoma is located in the nasal cavity in 75% of cases. The primary extra-nasal localization in the soft palate was exceptionally reported in the literature. Box: A 24-year-old male patient presented year isolated ulceration of the soft palate which developed rapidly in a month with inflammatory infiltration and extensive necrosis. Three deep biopsies confirmed the diagnosis of extranodal NK/T nasal cell type lymphoma. The palatal tonsils and parapharyngeal spaces were invaded. The patient died just after the first course of chemotherapy. Conclusion: Extranodal NK/T nasal cell type lymphoma is characterized by clinical polymorphism and poor prognosis. The management of this disease may benefit from the development of new chemotherapy drugs.

Introduction
The extranodal nasal type NK/T cell lymphoma, is a rare disease that affects mainly the nasal cavity and paranasal sinuses. It most frequently affects adults males of middle age, with a high prevalence in East Asia, where it is 3-10% of all malignant tumors. This lymphoma is the most common in the offspring of Indian women of Central and South America. The virus Epstein - Barr (EBV), plays an important role in the pathogenesis of this disease.

The extranodal nasal type NK/T cell lymphoma: tumor primitive, rare and aggressive soft palate Figure 1
Figure 1. Inflammatory thickening and infiltrating of the soft palate, with tissue necrosis.
The nasal extra achievement at the level of the upper aerodigestives tract may interest the ring of Waldeyer (38%), oral cavity (14%), larynx, hypopharynx (10%) and even the mandible or cheeks [1]. At the oral level, the nasal type NK/T Lymphoma exceptionally initially touches the soft palate (three cases have been described in the literature).

We report a new observation of T/NK very aggressive lymphoma having occurred in a young adult and who originally touched the soft palate.

Observation

A young adult of 24 years, consulted for a small superficial ulceration at bottom red, inflammatory, irregular contours interesting oral face of the soft palate which dates back to about 15 days prior to admission. This ulceration was evolving in a context of fever (at 38 ° C) and weight loss (loss of 15 Kg in two months) important. The patient showed no nasal symptomatology associated including no rhinorrhea, nasal obstruction or epistaxis. Examination of the upper aerodigestives tract, ulceration was hard, painful, rare in contact, on a soft palate undercover. The Palatine tonsils were normal appearance with cavum free. The rest of the clinical and endoscopic of the upper aerodigestives tract examination was within normal limits. There is no cervical, axillary or inguinal Lymphadenopathy. Somatic examination had revealed no other sign of appeal. Several diagnoses were suspected at the beginning of the disease, such as a viral infection (HIV) or bacterial (tuberculosis and syphilis). The negativity of the biological balance that has been achieved in this sense (TPHA, VDRL, HIV serology and search for BK were all negative) allowed to exclude the possibility of an infection of the soft palate. Local evolution was quickly marked by the appearance of an inflammatory thickening, infiltrating and crumbly all soft, bleeding Palace at the slightest touch with a necrosis which started at the free edge of the soft palate to destroy gradually his half less than a month and then extend to the Palatine tonsils, the cavum and parapharynges areas (figure 1). These endobuccales lesions were evolving in a context of significant alteration of the State overall, with anorexia, nasal obstruction with snoring, hypernasal and foul breath. This last symptomatology has been linked to the bacterial and mycotic necrotic tissue superinfection (negative bacilli and filament mycorrhizal). The patient was put on antibiotic and antifungal treatment for a period of 10 days without improvement. CT and MRI of the facial massif showed a significant thickening of the veil of the Palace and parapharynges areas (figure 2).

The extranodal nasal type NK/T cell lymphoma: tumor primitive, rare and aggressive soft palate Figure 3

Figure 3. The histologic appearance showing: (a) a proliferation of tumour cells of variable size, nuclei hyperchromatic enough monomorphic with mitotic figures. (b) a tumor proliferation who infiltrates an accessory salivary parenchyma (HE x 200).

Two deep biopsies of the soft palate with histopathological study were made on seven days ' interval, were inconclusive. A third biopsy preceded by excision of tissue necrosis including histopathological study referred to the diagnosis of a process lymphomateux (figure 3).

The extranodal nasal type NK/T cell lymphoma: tumor primitive, rare and aggressive soft palate Figure 4

Figure 4. The Immunohistochemistry shows a positive marking to antibodies: anti - CD3, anti - CD56, anti-Ki67, anti-CD4, anti-CD5, anti-CD8. Figure (4A): CD3x10, Figure (4b): CD4x40, Figure (4 c): CD5x40, Figure (4 d): CD8x4, (4) Figure: CD56x40, Figure (4f): Ki67x40.

A complementary immuno-operational study has concluded for the diagnosis of a lymphoma cells T - nasal type NK (figure 4)

(Positivity broadcasts antibodies anti-CD3, anti-CD56, positivity to the anti-CD5 on of few small T cells, to the anti-CD4 on many tumor cells, to the anti-CD8 on of few small lymphocytes, to the anti-Ki67 on 60% of tumor cells).

The bone marrow biopsy came back normal. The normal biological assessment at admission has worsened during the course of the disease: in pretherapeutique, he showed the blood, anaemia in 7, 5 g/dl of hemoglobin, white blood cells to 1000 item/dl and thrombocytopenia manifest 10 dl elements, the sedimentation rate was accelerated and the CRP has been very high, the LDH were high (734 IU/L), the liver balance sheet showed a remarkable cytolysis (ALT to 257 IU/L, AST to 213 IU/L). The search for the EBV in tumor cells by Immunohistochemistry was positive. The normal extension record in the first month after admission revealed the second month to the head and neck-best-abdominal-pelvic CT (HSM) hepatosplenomegaly of unknown nature in the absence of liver biopsy, but advocates a syndrome Activation macrophagique (SAM) to the association of the clinico-biological criteria (fever, hepatosplenomegaly pancytopenia, cytolysis). The patient was sent in Clinical Hematology where he received his first treatment of multidrug at base of SMILE (Dexamethasone: 40 mg/m2 on the 2nd and 4th day, Methotrexate: 2 mg/m2 on day 1, Ifosfamide: 1, 5 g/m2 on the 2nd and 4th day, L-asparaginase: 6000 U/m2 the 8th) (, 10th, 12th, 14th, 16th, 18th, Etoposide: 100 mg/m2 on the 2nd and 4th day). In the immediate course of this cure the patient was transferred into the service of resuscitation for hepatic encephalopathy where he died after a stay of 48 hours.

Discussion

Up to 75% of the cases of nasal type extraganglionnaires T/NK lymphomas occur at the level of the upper aerodigestives routes, mainly in the nasal cavity [2]. In 25% of cases the lymphoma T/NK seems extranasale original with oral localization in 2% of cases [3]. This pathology can affect patients at any age, but it is most common between 40 and 50 years old, so that our patient was only 24 years unlike other similar observations described in the literature or the age is a little more advanced (between 40 and) (60). It is to report a male predominance (sex ratio that varies between 2 and 4.5) [2].

Clinical polymorphism of the lesions and the rarity of this location (three cases reported in the literature: see table 1) are at the origin of the difficulties and delay diagnosis [4-6]. The bulk of the clinical symptomatology of a localization bucco-cavo-nasal pain, nasal obstruction, foul smell, rhinorrhea and bleeding. As in our case a thickening of the soft palate or posterior part of the hard palate may precede the formation of a deep necrotic ulceration, usually occupying a middle position extending to the nasopharynx to the oral cavity, and in the cavities naso-sinusiennes of the face. This ulceration grows, destroyed the Palatinate tissue and usually creates an oro-nasal fistula [2]. Some cases may be accompanied by a fever or other systemic symptoms, probably related with the local superinfection.

The rarity of this disease also poses the problem of differential diagnosis with deep fungal infections, the Wegener's Granulomatosis, tertiary syphilis, tuberculosis, other non-hodgkiniens lymphoma and epithelial tumors median malignant.

The pathogenesis of T/NK extranodal lymphoma of nasal type, remains unknown. However, it is strongly linked to EBV. The EBV is associated with a poor prognosis with a high rate of local recurrence, the possible extra-ganglionnaire extension and the development of the syndrome of activation macrophagique (SAM). The SAM is related to the activation of macrophages and T cells in particular, which leads to the consumption of the elements represented blood and hepatic and splenic infiltration (SAM protests have been reported in this observation form of a pancytopenia with HSM) [4]. Most of the dreaded complications (8 to 12% of the cases) are related to the secretion of cytokines by tumor cells, which often induces systemic symptoms such as fever and weight loss [4]. This symptomatology was part of the original procession in our case.

This aggressive lymphoma remains located in the primary site in many cases, with a weak regional ganglionic extension (15%-30%). The systemic spread from the primary site is rare (< 20%) [7]. the invasion of bone marrow is exceptional (3%).

The diagnosis of extranodal NK/T Lymphoma of nasal type must be mentioned in any patient from Asia or Latin America in the presence of necrotic lesions and extensive medians. Deep and repeated biopsy and biochemical tests help the diagnosis.

Histological aspects of extranodal NK/T Lymphoma of nasal type are similar regardless of the site of the injury. Histology is characterized by a dense and polymorphic, infiltration of inflammatory cells and tumour cells. Sometimes the tumor cells through the vascular wall penetration and their proliferation endoluminale, cause a vascular thrombosis with necrosis and tissue fibrosis.

The size and morphology of malignant cells can be variable and polymorphic.

Extranodal NK/T Lymphoma of nasal type cells express CD2 and CD3 intracytoplasmic (CD3e) Antigen. They always express the RNA of the EBV and cytotoxic molecules (TIA-1, perforine, granzyme B) [2]. There is often the CD56 antigen [2].

The absence of CD3s surface antigen or other markers of cells (CD4, CD5, CD8) T suggest that the lymphoma is authentic and native of NK cells.

With respect to chromosomal anomalies, the deletion of the long arm of chromosome 6 has been reported as the most common cytogenetic aberration (no genetic studies were made in our patient). In this region, two genes-PRDM1 and FOXO3-have been identified to be transferred and the lymphomagenese officials. The aberration of the FOXO3 gene is specific for extranodal NK/T Lymphoma of nasal type, but mutations in the gene PRDM1 are also found in other types of lymphomas [8].

CT is the test of choice to explore extranodal NK/T Lymphoma of nasal type. It allows the staging of the tumor by specifying its headquarters, the presence of an osteolysis and possible extension to adjacent structures. It is also interesting for falls assessment, the assessment of the response to treatment and monitoring.

The MRI shows more reliable in the study of the invasion of soft tissues, because it allows to differentiate the inflammation and swelling of the soft tissues of the tumoral invasion. MRI lesion is homogeneous with a low intensity to intermediate signal, which is iso-signal compared to muscles on the T1 weighted sequences and moderately hyper-signal compared to muscles on the T2 weighted sequences and hypo-signal by report to the mucosa. To gadolinium enhancement is also moderate and heterogeneous and is useful in assessing anatomical relationships of the tumor with intracranial structures.

When the extranodal NK/T Lymphoma diagnosis of nasal type is confirmed, a staging must be done before any treatment, including the physical exam looking for superficial Lymphadenopathy, hepatomegaly, or splenomegaly, chest x-ray, abdominal ultrasound, the best abdominal CT scan, biopsy of the bone marrow, gastrointestinal endoscopy, and the lumbar puncture, possibly in the presence of a lesion of the basis of the skull.

NK cells express the glycoprotein P MDR drugs so that the protocols containing anthracyclines are ineffective [9]. The treatment of no nasal lymphomas by the CHOP Protocol, radiotherapy, or their combination gives poor results [10]. Recently, a basic protocol of: dexamethasone, methotrexate, L-asparaginase, ifosfamide, and etoposide (SMILE) was designed specifically for these rare and aggressive locations [9].

Patients with no nasal Lymphoma treated with SMILE had a better rate of overall response with other chemotherapy protocols [10].

Current data indicate that no nasal lymphomas of all stages must be treated through systematic chemotherapy with radiotherapy to the site overrun if it is applicable [10].

The SMILE schema includes three drugs no P-glycoprotein dependent: dexamethasone, methotrexate and ifosfamide. L - asparaginase is incorporated into the treatment protocol for its activity in case of relapse or recurrence of the lymphoma [9]. Etoposide is included, because of its effectiveness in hemophagocytosis syndrome associated with NK cells or cells malignant T [9].

After radiation therapy at a dose of at least 50 Gy and 3 to 4 cycles of SMILE, the overall response rate can reach 90%, and the rate of complete response (CR) is around 70% [10].

The response to the Protocol SMILE is quick and is observed even after two priests. In addition, the remission is sustainable, with 90% of patients who are still in complete remission at follow-up [10].

Conclusion

This extranasale form of the nasal type NK/T lymphoma is distinguished by its clinical polymorphism, his aggression and his dark prognosis, which is further aggravated by the syndrome of macrophagique activation. Before such events, evoke the diagnosis and search for it would allow early diagnosis and management. This support is multidisciplinary and requires quick and real collaboration between doctors, ENT, hematologiste, pathologist and oncologist to effectively support as soon as these patients whose general condition continues to deteriorate