ARTÍCULOORIGINAL ORIGINAL ARTICLE

Characterization of lethal MANUSCRITOinjuries of the ACEPTADO facial middle line in patients of Hospital Escuela Universitario, Honduras between 2011-2014

Héctor Santiago Antúnez1,2, Vilma Díaz-Bonilla2,3, Roger Josué Ortega-Galo4, Nohely María Aguilar-Espinoza5, Cinthia Lizeth Martínez-Núñez4, Oscar José Varela-Carranza5

1. Specialist in Pathology, Universidad Escuela Universitario, Tegucigalpa. 2. Professor of Bachelor’s Degree at the Universidad Nacional Autónoma Honduras (UNAH). 3. Specialist in Otolaryngology, Hospital Escuela Universitario, Tegucigalpa. 4. Doctor of Medicine, Universidad Nacional Autónoma Honduras. Tegucigalpa. 5. Fifth Year of Pregraduate. Faculty of Medicine. Universidad Nacional Autónoma Honduras. Tegucigalpa.

CIMEL 2017; 22(1) 6-10

ABSTRACT Objective: To characterize lethal facial midline lesions, frequent signs and symptoms, gender and origin of the patients, histopathology and immunohistochemistry based on HEU institutional medical records between 2011 and 2014. Lethal midline injury is a syndrome that initially encompasses a variety of entities: non-Hogd- kin lymphomas of NK and T cells, non-Hogdkin B-cell lymphomas, autoimmune diseases such as granulomatosis with polyangiitis, many infectious and idiopathic causes with accelerated and catastrophic destruction of the nasopharyngeal region, and . Syndromes which are difficult to diagnose with very different therapeutic approaches.Methodology. A descriptive, cross- sectional study was carried out with a review of all biopsy registries performed in the Department of Pathological Anatomy of HEU from 2011 to 2014. 34 cases meet the inclusion criteria. Results: There was a higher prevalence in men 59%, within the age range of 19 to 59 years, with predominance of the central region of Honduras. Most frequent sign: obstructive mass. Most diagnosed was Non-Hodgkin’s lymphoma without specification. Conclusion: Frequency of lethal midline lesions is greater in males, mostly from the central region. The most frequent symptoms and signs are obstructive mass with ulceration and purulent ; the use of immunohistochemical markers is deficient to define nonspecific cases of Nasal Non-Hodgkin’s Lymphoma. Keywords: Lethal Granuloma of the Midline; Non- Hodgkin’s Lymphoma; Polyangiitis Granulomatosis (Source: MeSHNLM).

Please cite this article as: Santiago H et al. Characterization of lethal injuries of the facial middle line in patients of hospital Escuela Universitario, Honduras between 2011-2014. CIMEL 2017; 22(1): 6-10. DOI: https://doi.org/10.23961/cimel.v22i1.736

INTRODUCTION (2), a term introduced by the European classification of Lym- phomas in 2001 and accepted by the World Organization of is a clinicopathologic syndrome, Health in 2008 (6). Due to a nonspecific initial presentation, first described by Mc Bride in 1897, characterized by necro- lack of adequate suspicion, and lack of resources for im- tic ulceration, inflammation, and granulation of the central munohistochemistry, the differential diagnosis with entities facial region; (1,2) involving the upper airway, palate, and such as Wegener’s Granulomatosis, Carcinomas, Sarcomas, paranasal sinuses (3,4); formerly called midline pathological Mucocutaneous Leishmaniaisis, mycoses, among others; it granulomas (5). becomes a real dilemma since the apparent injuries of these other entities are similar under an untrained eye and have These lymphomas usually presents with signs and symptoms very different treatments (4, 9, 13). Depending on the correct of the nasal area spectrum: pain, epistaxis, , initial review carried out by the otolaryngologist, a doctor chronic rhinorrhea and sensation of respiratory obstruction, who often faces this syndrome, the ideal diagnostic and the- rapidly degenerating into septum perforation and bone ero- rapeutic course will be defined (6). sion (7-9). It is frequently described in immunocompetent men of Asian descent in Central and South America (10). Because of the increase in cases with suspicious granuloma- The Epstein Barr virus is strongly related to its pathogenesis tous lesions at the Hospital Escuela Universitario, the main (11,12). reference hospital in Honduras, a bibliographic search was carried out within the local and regional scientific literature, With the advances in immunohistochemistry, it was possible where the scarcity of case studies with frequency and patho- to categorize the majority of previously designated cases such logy studies in patient series in the last five years was reveal, as this syndrome towards extranodal T-cell lymphoma / NK

CIMEL 2017, Volumen 22, Number 1 ORIGINAL ARTICLE that’s why we considered it necessary to carry out the study months (Table 3). to update the findings and the particular characteristics of our patients affected by this syndrome in order to improve Table 1. Distribution of People with Lethal Injuries of the Facial diagnosis and follow-up. Midline according to Sociodemographic Characteristics, Hondu- ras, between 2011 and 2014, n=34. METHODOLOGY Characteristics N (%) Age (years) A descriptive, cross-sectional study was carried out where a 0-5 1 (2,9) total of 39,000 clinical records were reviewed with their co- 6-11 1 (2,9) rresponding biopsy results from the Hospital Escuela Uni- 12-17 0 (0,0) versitario between 2011 and 2014, according to the clinical 18-59 25 (73,6) criteria of midline fatal mortality, we chose the sample of 34 >60 7 (20,6) cases that met the diagnostic inclusion criteria histopatho- Average 40,5 logical Lymphoma of the nasopharyngeal region, with or Range 1-88 without immunohistochemistry; Granulomatosis with Po- lyangiitis and other neoplasms of the nasal region with non- Sex epidermoid origin. Cases of infectious etiology by fungi, Male 20 (58,8) protozoa and bacteria were excluded, and files with incom- Female 14 (41,2) plete clinical data were also eliminated. Location North Zone 5 (14,7) The data was collected in tables using Microsoft Excel with Central Zone 21 (61,8) gender, age, origin of the patient, symptoms, described signs, South Zone 8 (23,5) the evolution in months of the clinical picture and diagnostic methods. Subsequently, they were tabulated and synthesized Table 2. Distribution of People with Lethal Mid-Facial Line Inju- in frequency tables with a percentage using Epi Info 7. Ac- ries according to Most Frequent Signs and Symptoms, Honduras, cess to patient information was authorized by the heads of between 2011 and 2014, n=34. the , Pathology Department, Patient Characteristics N (%) Management Unit and Ethics of UNAH Faculty of Medical Symptoms Sciences. Pain 8 (23,5) Nasal Obstruction 11 (32,4) RESULTS Signs Among the selected cases we found a greater number of pa- Peri-orbital Edema 4 (11,8) tients within the age range of an economically active adult Epistaxis 16 (47,1) (73.6%), more prevalent diagnoses in males (58.8%), more Masa Exofítica Obstructiva 21 (61,8) than half of the reviewed from the central departments of Nasal Septum Perforation 15 (44,1) Honduras, although five of these patients reported coming Chronic Purulent Rhinorrhea 14 (41,2) from the same southern town: Nacaome, Choluteca. Other Ulceration 11 (32,4) sociodemographic results are reported in Table 1. Table 3. Distribution of People with Lethal Mid-Facial Line In- The most frequent reported symptom was the sensation of juries according to Onset of Symptoms at Diagnosis, Honduras nasal obstruction in a third of the sample, followed by pain; 2011 to 2014 n=34. the most observed and described sign in the records was the Disease Evolution (Months) N (%) appearance of an obstructive mass in the upper airway in 2/3 0-5 13 (38,2) of the selected patients. Other classic signs and symptoms of 6-11 6 (17,6) lethal midline granuloma syndrome are described in Table 12-23 9 (26,5) 2. >24 4 (11,8) Undetermined 2 (5,9) Regarding the time of evolution of symptoms and signs, tho- Average 9,4 se of short duration, less than 5 months, showed a prevalen- Range 0,5-48 ce above those longer than two years, with an average of 9

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The lack of immunohistochemical studies in 64.7%MANUSCRITO of the cases affection ACEPTADO than T-NK Non-Hodgkin Lymphomas. Three cases of whose histopathological diagnosis was positive for the syndrome undifferentiated sarcomas and two cases of Granulomatosis with is also described. The rest show variability of markers correspon- Polyangiitis are counted within the study findings due to the si- ding to the differential diagnoses (Table 4). milarity of their initial signs and symptoms with lymphomas. We highlight the absence of diagnostic specificity in the histological Table 4. Distribution of People with Lethal Mid-Facial Line Inju- subtype of lymphoma in twelve cases (35.3%). ries according to Immunopathological Diagnosis, 2011 to 2014, n=34. DISCUSSION Immunopathological Data N (%) With Immunohistochemistry 12 (35,3) Lethal midline injuries were described as endemically fre- CD 20 7 (58,3) quent in Asia and Central and South America. The preva- CD 45 5 (41,7) lence of Non-Hodgkin T-cell lymphomas / NK in the United States in the 2015 Kidwai study was 1.5% of all non-Hodgkin CD 3 5 (41,7) lymphomas (2, 10). In this study we found three cases, repre- CK 18 3 (25,0) senting 12% of all non-Hodgkin lymphomas and 8.8% of all CD 30 2 (16,7) those described (Table 5). EMA 2 (16,7) CMA 1 (8,3) Regarding the demographic variables (Table 1), a higher in- CDIS 1 (8,3) cidence of male sex was found in 59% of cases; data that re- No Immunohistochemistry 22 (64,7) sembles other investigations such as those of Tababi (16) and Niu (22). The age range with the most diagnosed individuals Histopathological diagnoses were individualized in Table 5. was the middle-aged adult population with 73.5% consistent with multiple studies from different geographic regions (1, 4, Table 5. Distribution of People with Lethal Mid-Facial Line Inju- ries according to Pathological Classification, 2011 to 2014, n=34. 8, 9, 15, 21). In the Central region of Honduras, it registered the highest number of cases by origin with 61.8%. Pathological Classification N (%) Neoplastics 34 (100) The symptoms most described in various studies cited as Lymphomas pain and nasal obstruction and signs such as edema, sep- Non-Hodgkin's Lymphoma tal perforation, epistaxis and rhinorrhea are nonspecific for B Cells each pathological entity that make up the syndrome (2, 3, 5, Smal cells 2 (5.9) 7, 9, 12, 14 , 21). Nasal obstruction marks as the most refe- Mixed cells 2 (5.9) rred symptom with 32.4%, compared similar to the studies Diffuse cells 5 (14.7) in China, India and Croatia (2, 7, 14). Lymphoplasmic 1 (3.0) Regarding the time of onset of symptoms at diagnosis of the T and NK cells 3 (8.8) cases studied, it was found that the greatest range of evolution Non-Specific 12 (35.3) of symptoms was between 0 and 5 months (38.2%), with a Hodgkin's Lymphoma 1 (2.9) general average of 9.4 months; value close to the means the Associated Immunodeficiency 1 (2.9) studies of Tababi et al and Miyake et al with 6 and 5 months Cutaneous pseudolymphoma 1 (2.9) respectively (6, 11). Sarcoma 3 (8.8) Wegener's Vasculitis 2 (5.9) Due to the institutional deficit of the Hospital Center where Regaud 1 (3.0) the data for this study were obtained, the diagnostic criterion No Neoplastics 0 (0.0) of immunohistochemistry was not completed in 64.7% and no markers for Epstein Barr virus were performed in any On average, 2 biopsies were performed per patient for the final sample due to the age of the patient tissue. Despite the abo- histopathological diagnosis, since the first ones described patterns ve, of the remaining confirmed 35.3%, CD20 positivity was of necrosis with an angiocentric pleomorphic infiltrate with or found in 7 cases and CD3 positivity in 5. Evidence of a pre- without inflammation, a non specific statement. dominance of non-Hodgkin lymphomas of B cells. Park et al The group of B-cell Non-Hodgkin Lymphomas with their clas- (16) concluded that lymphomas B cells in the nasopharyn- sifications presented three times more cases of nasopharyngeal geal cavity are more frequent than T / NK cells, thus remai-

CIMEL 2017, Volumen 22, Number 1 ORIGINAL ARTICLE ning rare. It differs from the study by Metgut et al (7). Table histochemistry and serology; The symptoms and findings of No. 5 is based on the 2008 REAL - WHO classification (6, physical examination and the histopathological descriptions 11, 22). of lethal midline granuloma are present in all cases.

Granulomatosis with polyangiitis was listed as a non-neo- It is worth noting the exclusion of different cases of infectious plastic cause of lethal midline injury (17, 21), it is frequent in and / or inflammatory etiology. Clinical suspicion is essen- middle-aged men, it presents with the same signs and symp- tial to address this syndrome, followed by timely biopsy and toms but the difference lies in the positivity of C- ANCA strict immunohistochemistry for this sample. Future studies (11) and thrombosis with vasculitis in biopsies (19); In this are required for the individual characterization of each type characterization, two cases of female patients confirmed by of nasopharyngeal neoplasm in our endemic population to serology and biopsy who underwent septal perforation were demonstrate unique traits in the Central American region. described. Sokołowska et al proposed granulomatosis with polyangiitis as a predisposing agent for the development of Financial support: Self-financed. lymphoma (15), so it was considered to include these cases Conflicts of interest: All authors have no conflicts of interest in the review for future research. Due to their similar clinical to declare. appearance, carcinomas and sarcomas of the nasal region were listed with their respective positive CK 18 and EMA Events presented: This research was presented in the form of immunohistochemical markers (9, 18, 21). a research protocol at the XV Congress of Scientific Research Students ASOCEM - UNAH, held in August 2016, winning The diagnostic difficulty is evidenced not only by the overlap the third prize in the category of research protocol. of symptoms and signs in more than five differential diagno- ses, but also in the number of biopsies required (6). 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Corresponding author:

Roger Josué Ortega-Galo E-mail: [email protected] Phone: 504 98866045

Received 08 October 2016 Accepted 13 October 2016

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