Oral Oncology (2005) 41, 340–348 http://intl.elsevierhealth.com/journals/oron/ REVIEW Idiopathic midline destructive disease: fact or fiction Juan Pablo Rodrigo a,b, Carlos Sua´rez a,b, Alessandra Rinaldo c, Kenneth O. Devaney d, Antonino Carbone e, Leon Barnes f, Dennis K. Heffner g, Alfio Ferlito c,* a Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain b Instituto Universitario de Oncologı´a del Principado de Asturias, Oviedo, Spain c Department of Surgical Sciences, ENT Clinic, Policlinico Universitario, University of Udine, Piazzale S. Maria della Misericordia, I-33100 Udine, Italy d Department of Pathology, Foote Hospital, Jackson, MI, USA e Division of Pathology, National Cancer Institute, IRCCS, Aviano, Italy f Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA g Department of Endocrine and Otorhinolaryngic/Head & Neck Pathology, Armed Forces Institute of Pathology, Washington, DC, USA Received 4 October 2004; accepted 15 October 2004 KEYWORDS Summary The differential diagnosis of a progressive destructive lesion of the mid- Idiopathic midline face and upper airway region includes both neoplastic and non-neoplastic entities; destructive disease; of these, the majority of cases prove to be either Wegener’s granulomatosis or lym- Midfacial granuloma phoma. Historically, these sorts of necrotizing midfacial lesions were diagnosed clin- syndrome; ically, and as a consequence a variety of overlapping categories of disease sprang up. Wegener’s As pathologic examination of biopsy material became both more widespread and granulomatosis; (particularly in the last several years) more sophisticated, many lesions previously Malignant lymphoma thought to be of mysterious origins have proven to be examples of lymphoma (in par- ticular, sinonasal natural killer cell or T cell [NK/T] lymphomas). At present, the evaluation of a patient with a progressive destructive process involving the midface region should include imaging studies (to delineate the extent of disease) as well as biopsy (with sampling of lesional tissue for application of sophisticated testing—including immunohistochemical studies, flow cytometry, or molecular studies as necessary—to exclude the possibility of a NK/T cell lymphoma). There * Corresponding author. Tel.: +39 0432 559302; fax +39 0432 559339. E-mail address: [email protected] (A. Ferlito). 1368-8375/$ - see front matter c 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2004.10.007 Idiopathic midline destructive disease: fact or fiction 341 remain occasional patients whose necrotizing midfacial lesions continue to be dif- ficult to classify despite the application of extensive testing; such patients are sometimes described as suffering from the nebulous entity of ‘‘idiopathic midline destructive disease’’. While it remains to be seen whether such patients will ulti- mately be assigned to other diagnostic groups (as, for example, occult toxic inju- ries—as in the case of cocaine abusers who are not forthcoming with regard to their drug usage), it seems likely that ‘‘idiopathic midline destructive disease’’ is a diagnostic term of questionable validity which should be used only with extreme reticence in modern practice. c 2004 Elsevier Ltd. All rights reserved. Introduction History The term ‘‘midline granuloma syndrome’’ or ‘‘mid- At the meeting of the Laryngological Society of facial granuloma syndrome’’ are clinical terms that London on 9 December 1896, McBride4 showed pho- encompass a broad spectrum of diseases character- tographs of a patient with progressive destruction ized by a progressive (and, often fatal) ulceration of the face and nose. Under the heading of ‘‘malig- and destruction of the upper airway, with involve- nant granuloma’’, Woods5 described two patients ment of the nose, the paranasal sinuses, oral cavity in 1921 with a progressive ulcerated lesion of the and the soft tissues of the face. Over the years, oronasal region; lacking, however, was a clear there has been confusion over the various terms description of the pathological appearances. In used to refer to this clinical condition: malignant 1929, Kraus6 reported three patients with granulo- granuloma, granuloma gangraenescens, progres- mas and extensive destruction of the nose, oral sive lethal granulomatous ulceration, lethal mid- cavity and pharynx and suggested the diagnostic line granuloma, non-healing midline granuloma, term ‘‘granuloma gangraenescens’’. In 1933, Stew- polymorphic reticulosis, midline malignant reticu- art7 extensively reviewed the disease, which be- losis, idiopathic midline granuloma, lymphomatoid came known as Stewart’s syndrome. The best reticulosis, and others have all been employed to known term, ‘‘lethal midline granuloma’’ was describe progressive ulceration and destruction of introduced by Williams8 in 1949, to describe the midfacial region.1 inflammatory destructive lesions with no known The histopathologic classification of these etiologic factors. destructive lesions has undergone substantial revi- The histopathologic features of some of these sion in the last years. Now it is known that, after lesions were studied by Friedmann9 who, after exclusion of granulomatous infections and neopla- eliminating infectious and neoplastic diseases, pos- sias, the differential diagnosis of midfacial destruc- tulated the existence of two entities, the Wege- tive processes includes the following entities: ner’s and the Stewart’s type of midline Wegener’s granulomatosis (WG), malignant lym- granuloma. In the first one, a giant cell inflamma- phoma, Churg-Strauss syndrome, microscopic poly- tory granulomatous infiltration was present, angitis and drug abuse. Currently there is doubt whereas in the second the infiltrate was more pleo- about the existence of idiopathic midline destruc- morphic, with or without histiocytic cell predomi- tive disease (IMDD), and some authors think that nance. Later, Eichel et al.10 recognized a possible after exclusion of WG nearly all remaining cases relationship between these latter lesions to pri- presenting as midfacial granuloma syndrome are mary non-Hodgkin’s lymphoma of the nose, and non-Hodgkin’s lymphomas2,3—in particular, the coined the term ‘‘polymorphic reticulosis’’, refer- subtype of angiocentric NK/T-cell lymphoma. Each ring to a mixed infiltrate of lymphoreticular cells. of these diseases has its own treatment and as a In 1977, Michaels and Gregory11 reexamined histo- consequence, older descriptive terms should be re- logic sections from 30 patients who had previously placed by the pathologic diagnosis that accurately been clinically diagnosed as malignant granuloma; describes the disease entity to avoid inappropriate of these, 10 showed features of malignant lym- therapy. phoma. Therefore, at this point, the histopathol- In this review, the clinico-pathological charac- ogy of midline granuloma syndrome included: teristics, diagnosis and therapy of ‘‘midfacial gran- WG; polymorphic reticulosis; and conventional uloma syndrome’’ are revisited. lymphoma of the nose.12,13 In 1982, Tsokos 342 J.P. Rodrigo et al. et al.14 identified an additional group of patients fied as nasal-type extranodal NK/T-cell with midline granuloma syndrome who had distinc- lymphoma.18 tive clinico-pathologic features and which were aggregated under the term ‘‘idiopathic midline destructive disease’’. This was characterized as a locally destructive lesion limited to the upper Clinical features respiratory tract and with no systemic involve- ment. The pathologic hallmark was the presence Cases of midline destructive disease (Figs. 1–5) of non-specific inflammation and necrosis with ab- present over a wide age range, peaking in the sixth sence of granulomas and malignant cells. decade, with males predominating. Non-Hodgkin’s During the 1980s, the advances in immunohisto- lymphoma of the midface region is one of the rar- chemical phenotyping and in molecular genetics fi- est forms of extranodal lymphoma in the Western nally permitted a more detailed characterization world, representing less than 0.5% of cases. The of the cell origin in these cases of midfacial incidence of these tumors is much higher among destructive diseases. It was now possible to demon- Asian and Southern and Central American popula- strate the monoclonal (neoplastic) lymphoid origin tions, where most of the cases are of the T-cell of the atypical cells in polymorphic reticulosis.15 or NK-cell phenotype.17,19 The term ‘‘angiocentric’’ lymphoma was used to The initial symptoms are usually those of a non- describe these nasal lymphomas, with the term specific rhinitis or sinusitis (with nasal obstruction ‘‘angiocentric’’ referring to the invasion by lym- and nasal discharge). Epistaxis and facial swelling phoma cells of blood vessels with destruction of may enter into the clinical spectrum as well. With blood vessel wall, leading to the widespread disease progression, ulcerations spread, destroying necrosis.16 the soft tissues, cartilage and bone. Subsequently, All of these lymphomas were originally believed facial pain and facial deformities develop. Patients to have a T-cell origin; however, more recently, it may also demonstrate signs which stem from infil- has become apparent that many of them originate tration of local structures, such as cranial nerve from natural killer (NK) cells.17 These NK cells palsies or diplopia and proptosis due to intra-orbi- share many phenotypic features with T-cells and tal or skull base extension. Similar destruction