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Scott Troob, MDEmail: scott.troob@nyumc.orgPhone: 212-562-3551

Objective: Describe an especially rare case, primary natural killer (NK) T Cell lymphoma of the supraglottis. Due to its unique presentation and infrequent occurrence, treatment in this case was delayed while awaiting a definitive diagnosis. Presentation of this case and the review of the literature should aid in the differential diagnosis.

Methods: The patient's medical records including his clinical history, laboratory, radiologic, and pathologic data were reviewed. Additionally, a literature search was performed for cases of laryngeal lymphoma, with special attention to NK T-cell type.

Results: A 22-year old male from South America presented with two months of odynophagia, hoarseness, fever, hemoptysis, night sweats and a 70-pound weight loss. Work up for tuberculosis, HIV and serologies for systemic granulomatousconditions were negative. Otolaryngologic evaluation demonstrated normal-appearing nasal mucosa and oral cavity. Laryngoscopy revealed a thickened epiglottis with polypoid mucosa of the vallecula and the supraglottis. Biopsy of the epiglottis demonstrated NK T cell lymphoma, nasal-type with CD3 and CD56 positivity and histologic features of an aggressive EBV-associated form. Imaging and bone marrow biopsy confirmed its confinement to the supraglottis. He is currently undergoing concurrent chemo-radiation therapy.

Conclusion: Lymphoma of the larynx represents 1% of malignant laryngeal tumors. Primary laryngeal NK T cell lymphoma with disease isolated to the larynx is exceptionally rare and has not previously been reported. Medical work up to rule out infectious or inflammatory lesions along with directed biopsies should help in the diagnosis.

Primary Natural Killer T Cell Lymphoma of the SupraglottisScott H Troob, MD1; David R Friedmann, MD1; Cynthia Liu, MD, PhD2; Maria Suurna MD1

1Department of Otolaryngology – Head & Neck Surgery, New York University School of Medicine, New York, NY 2Department of Surgical Pathology, Hematopathology, and Molecular Pathology, New York University School of Medicine, New York, NY

• A 22-year old male tombstone carver from El Salvador, who immigrated to the United States two years earlier, presented to the Bellevue Emergency room complaining of two months of cough, hemoptysis, fever, dysphagia, odynophagia, hoarseness, night sweats and a 70-pound weight loss.

• On initial fiberoptic examination in the ER the patient’s nasal cavity and nasopharynx where clear, however ulcerative polypoid changes of the epiglottis were noted

• Computed tomography of the neck and chest revealed a thickened epiglottis, a normal larynx, extensive air in retropharyngeal space extending to the mediastinum, evidence of prior granulomatousdisease, and a retained bullet in the right lung parenchyma. No cervical lymphadenopathy was appreciated.

• Esophagram failed to reveal evidence of perforation.

• In the coming days, the patient was taken to the operating room for panendoscopy, where ulcerative polypoid lesions isolated to the epiglottis were biopsied. Based on the presentation and endoscopy, the ENT service was highly suspicious of laryngeal tuberculosis.

• Work up for tuberculosis (sputum AFB, serum quantiferon, PPD), HIV, and serologies for systemic granulomatous conditions (serum ACE, C-ANCA, P-ANCA) were all negative.

• NK T-cell lymphoma, formerly known as lethal midline granuloma or angiocentric lymphoma, is an extranodal lymphoma that may present in the head and neck. It most often occurs in the paranasalsinuses and nasal cavity of young to middle age men. As seen in our patient, tissue necrosis is common, and is thought to be secondary to perivascular invasion and vascular occlusion. Unlike the classic presentation, our patient did not have involvement of either the nasal cavity or paranasal sinuses.

• Extranodal involvement occurs in approximately 25% of lymphoma. When such involvement occurs in the larynx, it most often develops in the lymphoid collections in the lamina propria and ventricles of the supraglottic region. A recent review of primary laryngeal lymphoma of the larynx places the mean age of onset in the 7th decade of life (range 4-81 years). Patients often present with complaints of hoarsness, cough, dysphagia, globus senstation, and stridor. Weight loss and fever are also common.

• Radiographically, laryngeal lymphomas demonstrate homogenous contrast enhancement, most often centered in the submucosa of the supraglottis. Extension of these lesions to the oropharynx and nasopharynx has also been described.

• In retrospect, though several clinical and radiographic features of this case were suggestive of the final pathology, it was ultimately the immunohistochemical evaluation that made the diagnosis.

The patient's medical records were reviewed, including the clinical history, laboratory, radiologic, and pathologic data. Additionally, a literature search was performed for cases of laryngeal lymphoma, with special attention to NK T-cell type.

Lymphoma of the larynx represents 1% of malignant laryngeal tumors. Primary laryngeal NK T cell lymphoma with disease isolated to the larynx is exceptionally rare. Medical work up assists in ruling out infectious or inflammatory lesions. Radiographic data, directed biopsies, and immunohistochemical stains can confirm the diagnosis.

Primary hematopoietic neoplasms of the larynx are rare. Squamous cell carcinoma represents greater than 95% of all malignant laryngealneoplasms. Other malignancies of the larynx include verrucouscarcinoma, adenocarcinoma, adenocystic carcinoma, spindle cell carcinoma, the neuroendocrine tumors, mucoepidermoid carcinomas, sarcomas, granular cell tumors, and rare metastatic carcinomas. Infectious laryngeal lesions caused by organisms such as tuberculosis, syphilis, klebsiella rhinoscleromatis, mycobacterium leprae, and several varieties of fungus may assume the appearance of laryngeal malignancy. Systemic diseases such as sarcoidosis, Wegner’s granulomatosis, and amyloidosis should also be considered in the differential diagnosis of laryngeal lesions. Hematopoietic neoplasmsconstitute less than 1% of all laryngeal tumors. Plasmatocytoma is the most common, followed by lymphoma – with fewer than 100 reported cases. Of these, diffuse large B-cell and extranodal marginal zone lymphoma (MALT lymphoma) are the most common. Primary laryngeal lymphomas have been infrequently reported, making their diagnosis challenging.

Introduction

Methods

1. Ansell SM, Habermann TM, Hoyer JD, Strickler JG, Chen MG, McDonald TJ. Primary laryngeal lymphoma. Laryngoscope. 1997 Nov;107(11 Pt 1):1502-6.

2. Pak MW, Woo JK, Van hasselt CA. T-cell non-Hodgkin's lymphoma of the larynx and hypopharynx. Otolaryngol Head Neck Surg. 1999 Sep;121(3):335-6.

3. Nayak JV, Cook JR, Molina JT, Branch MP, Branstetter BF 4th, Ferris RL, Myers EN. Primary lymphoma of the larynx: new diagnostic and therapeutic approaches. ORL J Otorhinolaryngol Relat Spec. 2003 Nov-Dec;65(6):321-6.

4. King AD, Yuen EH, Lei KI, Ahuja AT, Van Hasselt A. Non-Hodgkin lymphoma of the larynx: CT and MR imaging findings. AJNR Am J Neuroradiol. 2004 Jan;25(1):12-5.

5. Word R, Urquhart AC, Ejercito VS. Primary laryngeal lymphoma: case report. Ear Nose Throat J. 2006 Feb;85(2):109-11.6. Tardío JC, Moreno A, Pérez C, Hernández-Rivas JA, López-Carreira M. Primary laryngeal T/NK-cell lymphoma, nasal-type: an

unusual location for an aggressive subtype of extranodal lymphoma. Eur Arch Otorhinolaryngol. 2008 Jun;265(6):705-8.7. Monobe H, Nakashima M, Tominaga K. Primary laryngeal natural killer/T-cell lymphoma--report of a rare case. Head Neck. 2008

Nov;30(11):1527-30.8. Markou K, Goudakos J, Constantinidis J, Kostopoulos I, Vital V, Nikolaou A. Primary laryngeal lymphoma: report of 3 cases and

review of the literature. Head Neck. 2010 Apr;32(4):541-9. Review.

CONCLUSIONS

DISCUSSIONResults - Case Presentation

REFERENCES

Figure 5. Low power photomicrograph of pathologic specimen.

Squamous mucosa with lymphoid aggregate

Figure 8. Positive CD56 staining

Figure 1. Axial CT revealing asymmetric thickening of epiglottis with submucosal

enhancement, air in retropharyngeal space

Figure 2,3,4. Endoscopic view of ulcerative polypoid epiglottis with uninvolved glottis and subglottis

ABSTRACT

CONTACT

• Initial pathologic examination revealed ulcerative benign squamousmucosa and an adjacent dense lymphoid component with cytologicatypia. Hematopathologic evaluation described necrotic tissue, squamous mucosa with a dense atypical large cell lymphoid infiltrate. Immunohistochemical stains revealed the majority of the large cells to be CD3 (T and NK cell marker) and CD56 (NK cell marker) positive. The large cells where also positive for Granzyme-B (expressed by cytotoxic T lymphocytes and NK cells). In situ hybridization for EBV was strongly positive in the tumor cells. Molecular studies utilizing DNA extraction from paraffin embedded samples detected T-cell receptor gene rearrangements. Final pathologic diagnosis was stated as extranodal NK/T-cell lymphoma.

• Bronchoalveolar lavage and bone marrow biopsy were both negative.

• PET/CT revealed increase glucose metabolism in the region of thesupraglottis extending to the oropharynx with a maximum standard uptake value of 11.9.

• The patient received 6 weeks of radiation therapy and 3 cycles of chemotherapy - DeVIC (dexamethasone, VP16, ifosfamide, carboplatin). At 6 months follow up, he is clinically and radiographically without evidence of disease.

Results - Case Presentation

Figure 9. In situ hybridization forEBV strongly positiveObjective

This presentation describes a rare case of primary natural killer (NK) T Cell lymphoma of the supraglottis. Due to its unique presentation, treatment in this case was delayed until a definitive diagnosis was made. Presentation of this case and the review of the literature should aid in the differential diagnosis.

Figure 7. Positive CD 3 staining

Figure 6. Higher power photomicrograph with dense atypical large cell

lymphoid population