Le Infezioni in Medicina, n. 3, 164-172, 2008 Casi clinici Associated and rhinopharyngeal Case reports adenocarcinoma during HIV infection: diagnostic and therapeutic issues Associazione patologica tra actinomicosi ed adenocarcinoma del rinofaringe in corso di infezione da HIV. Aspetti diagnostici e terapeutici

Sergio Sabbatani1, Ciro Fulgaro1, Gino Latini2, Marcellino Burzi3, Roberto Manfredi1 1Department of Infectious Diseases, “Alma Mater Studiorum” University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; 2Department of Otolaryngology, Maggiore General Hospital, Bologna, Italy; 3Department of Radiology, Maggiore General Hospital, Bologna, Italy

■ INTRODUCTION years, after the availability of cART [1-5]. The d- ifferential diagnosis and therefore the treatment hanks to the introduction of potent regi- of these disorders are usually delayed and ham- mens of combined antiretroviral therapy pered by co-existing disorders, especially chron- T(cART), since mid-1996 the frequency of op- ic-relapsing infectious complications, related or portunistic infections had a dramatic decline a- unrelated to the eventual, underlying HIV-asso- mong HIV-infected patients, and the life ex- ciated immunodeficiency [1-5]. pectancy of this patient population significantly In particular, among neoplastic complications increased. At the same time, due to the increased of the ear, nose, and throat (ENT) districts, mean age of HIV-infected population, and a se- those affecting the nose and the rhinopharynx ries of potential supporting factors (i.e. persist- remain somewhat rare among HIV-infected pa- ing immune system imbalance, exposure to tients, with extranodal lymphomas burdened drugs and carcinogenic substances, continued la- by a series of possible local complications, pre- tency of potentially oncogenic viruses, HIV in- vailing over squamous adenocarcinoma and fection itself), haematological and especially sol- other solid tumours, differently from the dis- id organ malignancies showed a proportional in- ease distribution found in the general popula- crease during time. As a consequence, besides tion [6-8]. the traditionally reknown AIDS-related cancers The diagnosis of tumour-like rhinopharyngeal (i.e. Kaposi’s sarcoma, non-Hodgkin’s lym- lesions remains difficult when an expected lym- phoma, and primary central nervous system lym- phocyte-monocyte hyperplasia involving the phoma, together with cervical cancer added to local lymphoid districts occurs in HIV-infected the list since the year 1993), there is a worldwide subjects, who are prone to show a reactive lym- emergence of broad-spectrum haematological phoid proliferation descending from HIV dis- and especially solid organ neoplasms, which al- ease itself, and eventual concurrent infections, so seem to occur at a younger age, and encom- like that caused by Epstein-Barr virus [6-8]. pass a greater aggressivity and a more frequent Moreover, slowly progressive infections possi- and more rapid mortality compared with the bly caused by a large spectrum of pathogenic general population [1-3]. The possible occurrence microorganisms (especially atypical mycobac- of multiple (concurrent or subsequent) malig- teria, and ), may oc- nancies, has been also reported during recent cur as space-occupying masses of the nose

164 2008 and/or the rhinopharynx [9]. They tend to ■ CASE REPORT mimick other local complications, including neoplastic ones, and remarkably complicate the A 49-year-old male ex-i.v. drug user was diag- differential diagnostic process of these lesions. nosed with HIV infection since 13 years, while Finally, similarly to the occurrence of tobacco a concurrent chronic HCV hepatitis was dis- smoking as a known risk factor of upper closed since 10 years. Due to a very low com- aerodigestive tract malignancies, also a pro- pliance to clinical and laboratory controls, both longed exposure to recreational substances (in- antiretroviral therapy and chemoprophylaxis cluding inhalation of drugs like cocaine and against the most common HIV-associated op- heroin), has been described as a possible sup- portunistic infections were denied by our pa- porting factor of rare, anecdotal cases of het- tient during his first three years of follow-up, erogeneous tumours of the nasal cavity among when active drug addiction was still present. HIV-infected subjects, with or without local su- Ten years ago, our patient was hospitalized ow- perinfections caused by the coexistence of ul- ing to the development of an AIDS-defining ill- cerative mucosal lesions, and a varied resident ness (neurotoxoplasmosis). At that time, he ex- flora colonizing the upper respiratory tract [10- perienced his nadir of absolute CD4+ lympho- 12]. With regard to the lesions of the nasal sep- cyte count (36 cells/µL only). tum and nasal cartilage and sinusal bone tis- After successful cure of this central nervous sue, when excluding congenital lesions, all ac- system opportunistic complication, our patient quired ones usually show aspecific imaging finally accepted a combined antiretroviral ther- findings also at sophisticated study techniques, apy (cART), initially conducted with didano- like X-ray films, computerized tomography sine, stavudine, and indinavir, together with a (CT) scans, magnetic resonance imaging (MRI), secondary prophylaxis for toxoplasmosis, car- and so on. ried out with cotrimoxazole, in order to prevent These lesions may be caused by a very broad a pneumocystosis, too. Despite a limited adher- spectrum of causes, including nasal trauma (in- ence to antiretroviral therapy (not exceeding volving surgical interventions and invasive di- 70-80% of recommended doses, as assessed on agnostic procedures, accidents, but also the ground of spontaneous patient’s declara- rhinotillexomania), exposure to toxic sub- tions, and monthly drug accountability carried stances (including local decongestants and in- out at our dedicated HIV outpatient service), a haled cocaine or other drugs), inflammatory progressive recovery of the CD4+ count at lev- diseases (i.e. sarcoidosis, reparative granulo- els above 200 cells/µL, allowed the discontinu- mas, Wegener’s granulomatosis, and other col- ation of cotrimoxazole prophylaxis eight lagen vascular diseases), multiple infection months after hospital discharge. Even though a (caused by , mycobacteria, fungi, or as- complete suppression of HIV viremia was sociated microorganisms), or malignancies reached after the first six months of cART, it (whose large spectrum of disorders includes was never sustained subsequently, probably carcinomas, sarcoma, Pindborg tumor, angiofi- due to the limited patient’s adherence to differ- broma, hemangioma, neuroendocrine tumor, ent, alternative regimens of cART proposed in schwannoma, and primary or secondary le- order to enhance his adherence. During the sions of lymphoproliferative disorders) [12]. subsequent laboratory follow-up, plasma HIV- Aim of our present report is to describe an ex- RNA levels ranging from 450 and 4,300 tremely rare occurrence of associated rhinopha- copies/mL were disclosed, in absence of fur- ryngeal actinomycosis and squamous adeno- ther occurrences of negative viremia. carcinoma in a HIV-infected patients treated During the further follow-up until recently, our with cART and with some specific and local patient progressively abandoned i.v. drug ad- risk factors (cigarette smoking, long-term in- diction but resorted to a “recreational”, inhala- halatory substance abuse, and a half-profes- tory use of both cocaine and heroin. Moreover, sional mushroom-truffle search and evaluation he continued a personal semi-professional hob- by smell). by regarding frequent mushroom and truffle The histopathological and imaging diagnostic search, and continued tobacco (cigarette) smok- work-up of our patient’s disease, and its thera- ing, which lasted since the age of 16 years. peutic and outcome features, are presented and Despite low adherence levels to four different discussed on the ground of the available litera- lines of cART, the stable and sufficiently satis- ture evidences. factory immune recovery, as established by a

165 2008 CD4+ count always above 400 cells/µL (above systemic broad-spectrum antibiotic treatment, 26-30% of total T-lymphocytes, with a peak val- associated with non-steroideal anti-inflamma- ue of 486 cells/µL in the year 2003), and the tory drugs and mucolytics. After repeated ENT negligible clinical history, allowed our patient specialistic consultations, our patient under- to maintain his low-adherence cART regimen, went a contrast-enhanced CT scan and MRI of until a genotypic resistance testing of 12 the face and brain, which pointed out an ag- months ago performed with rising plasma HIV- gressive form of rhinitis and sinusitis, with a se- RNA levels (5,190 copies/mL). This last viro- vere inflammatory involvement of maxillary logical assay detected multiple nucleo- and ethmoidal sinuses (Figures 1 and 2). side/nucleotide resistance mutations, complete Subsequently, a fiberoptic rhinoscopy (Figure resistance to both available non-nucleoside re- 3) with associated multiple biopsies, culture, verse transcriptase inhibitors, and multiple pro- and histopathological examination, disclosed a tease inhibitors resistance mutations, so that a predominantly necrotic tissue with abundant cART regimen including lamivudine, abacavir, fibrin deposition, and actinomycosis-like “sul- and fosamprenavir-ritonavir was introduced phur” granules surrounded by a relevant three months before the occurrence of the pre- monocyte-macrophage cell infiltrate. Culture sent disease, although patient’s adherence lev- search for aerobe pathogens, fungi, and my- els remained unsatisfactory. cobacteria tested negative. Three months after the introduction of the last Based on this diagnosis of actinomycosis, a spe- therapeutic line, when HIV-associated virologi- cific antimicrobial treatment with oral amoxy- cal and immunological parameters showed a cillin-clavulanate was started, and changed af- CD4+ lymphocyte count of 418 cells/µL, and a ter seven days with i.v. imipenem (at 1 g, twice plasma viremia of 2,620 HIV-RNA copies/mL, daily), for further 25 days, but local manifesta- our patient started to complain of severe suba- tions did not improve, as well as local tender- cute sinusitis-rhinitis-like signs and symptoms, ness and nasal discharge, so that a surgical ap- including mucous-purulent discharge (pre- proach to the lesion was established together dominantly from the left naris), poorly con- with ENT consultants. The ENT surgical inter- trolled by local and inhalatory therapy, and a vention included a left anterior ethmoidecto-

Figures 1 and 2 - Contrast-enhanced CT scan and gadolinium-enhanced magnetic resonance imaging (MRI). A solid mass with dishomogeneous enhancement, which occupies the whole nasal cavity, is demonstrated.

166 2008 Figure 3 - Endoscopic examination, carried our by a fiberoptic instrumentation. The left nasal fossa is com- pletely occupied by a tissue of solid macroscopic appearance. The implant/cleavage basis cannot be defined. my, a left meatotomy, and a thorough revision HIV viremia after 5 weeks (HIV-RNA below 40 of the left nasal fossa, where a solid neoforma- copies/mL), while our patient’s CD4+ count tion was removed. The histopathologic exami- dropped and remained around 200-250 cells/µL. nation of this surgical specimen surprisingly During the intensive ENT follow-up, a further showed the concurrence of a poorly differenti- fiberoptic endoscopy was performed two ated squamocellular carcinoma, with concur- months after the first diagnosis of malignancy, rent basaloid aspects, together with Actino- and multiple ethmoideal biopsy studies myces-like bacterial colonies. Although regional demonstrated the persistance of an intense, adenopathic involvement was excluded, after subacute inflammatory process, without evi- diagnosis a local, large, stage T3 neoplasm, a dence of specific infection, and without evi- combined radiotherapy-chemotherapy regi- dence of residual local cancer lesions, at both mens was started, after Oncology consultation. microbiological and histopathological studies. A local radiotherapy was started and continued One month later, a sudden deterioration of clin- for two months, together with a concurrent ical and neurological conditions were interpret- chemotherapy (i.v. cysplatinum at 100 mg/m2 ed as signs and symptoms of a severe central administered after the days 1, 22, and 43 of ra- nervous system involvement, rapidly worsen- diotherapy cycles). ing into a deep comatous state, and an over- The concomitant cART, although taken again whelming cachexia, which led our patient to with limited compliance, was changed into an death in two weeks. A further contrast-en- association of tenofovir, emtricitabine, and hanced TC scan obtained a two weeks before atazanavir-ritonavir, which led to a negative patient’s death demonstrated a diffuse nodular

167 2008 From a bacteriological point of view, although israelii is the most frequent mi- croorganism responsible of human actinomyco- sis, other species (including Actinomyces naes- lundii, Actinomyces viscosus, Actinomyces odon- tolyticus, and the close species Arachnia propioni- ca), have been anecdotally reported in human disease [13, 14]. Historically mistaken with fun- gi because of their light microscopic aspect, and their difficulty to grow in regular mediums and aerobic conditions, Actinomyces spp bacteria are typically environmental in origin, since they represent saprophytic organisms usually found in the soil and dust, but they are also capable of colonizing the oral cavity, especially when poor oral hygiene and underlying dental and paro- dontal diseases are of concern, as in drug ad- dicts. Sparse cases of cervical-facial actinomy- cosis have been attributed to nasal trauma or surgical manipulation, too [13, 14]. Actinomy- cosis is diagnosed with a positive culture (which actually is very difficult to be obtained in the current clinical practice, due to the fas- Figure 4 - Contrast-enhanced computerized tomo- tidious culture requirements, and the need to graphy (CT) scan of the brain obtained two weeks rely on a very rapid transportation to a special- before patient’s death. Numerous, diffuse nodular ized laboratory, and an immediate incubation lesions of the basal nuclei, markedly enhanced by in microaerophilic or anaerobic environment), contrast, some of them showing an evident sur- rounding oedema, represent the sign of end-stage so that the diagnosis is more often obtained by neoplastic dissemination to the brain. detecting the typical colonies and “sulfur” granules in histopathologic specimens. In its typical involvement of cervical-facial lesions of the basal nuclei, markedly enhanced structures, the clinical appearance of actinomy- by contrast, some of them complicated by an cosis may vary from enlarging, painless, firm evident surrounding oedema, interpreted as or fluctuant swelling, either complicated or not secondary spread of the primary rhino-sinusal by ulcerated lesions [11, 13, 14]. The late evolu- carcinoma (Figure 4). tion towards multiple mucous-cutaneous fis- tulizations draining the typical “sulphur” granules is frequently a diagnostic clue. Radio- ■ DISCUSSION logical examination and other imaging tech- niques (CT and/or MRI) of the paranasal si- Actinomycosis is a rare human disease caused nuses and the nose allow to exclude osteolytic by slow-growing, anaerobic, filamentous, processes (typical of a malignant process), and Gram-positive, catalase-negative organisms, are very useful prior to the unavoidable resort which usually involves the cervical-facial re- to invasive diagnostic techniques, which is es- gion including the oral cavity, paranasal sinus- sentially based on multiple biopsy, and culture es, parotid glands, orbit, neck, and anatomical- together with histopathology, and prior to the ly close regions where the infection spreads frequent surgical excision [12, 15]. In fact, save from contiguous areas. Only a few reported limited episodes, the treatment of choice is episodes of actinomycosis involve the lower based on a surgical exeresis of the entire lesion respiratory tract (the so-called thoracic form), with debridement of necrotic tissues, associat- and the gastrointestinal tract (the so-called ab- ed with a long-term antibiotic treatment, car- dominal form), after a primary focus usually lo- ried out with beta-lactam derivatives, which calized in the upper airways. Hematogenous are effective against bacteria belonging to dissemination and distant foci of infection are Actinomyces spp. extremely rare. When considering actinomycosis and the ENT

168 2008 districts, the slow, indolent progression of these fection, including an isolate case of esophageal atypical bacterial lesions pose unavoidable actinomycosis complicated by multiple, non- problems of differential diagnosis, also reflect- healing organ ulcers, and an episode of pul- ing into a frequently delayed management. For monary actinomycosis secondary to bacteremic example, four episodes of nasal-rhinopharyn- dissemination [26, 27]. In only one case, a nasal geal actinomycosis just imitating nasopharyn- actinomycotic mass was concurrent with sec- geal carcinoma have been successfully cured af- ondary lesions from an underlying malignant ter prolonged antibiotic therapy only (without disease (choriocarcinoma) in a patient with HIV resorting to surgery), as reported in 2000 by infection, while no cases of associated actino- Chaing et al. [16]. Another anecdotal report of mycosis plus a local, underlying squamous cell nasopharyngeal actinomycosis occurred in adenocarcinoma of the same ENT district have 2004 but surgical debridement became neces- occurred until now in both HIV-infected and sary to ensure cure, together with long-term an- HIV-non-infected subjects, to the best of our timicrobial treatment [17]. Moreover, actinomy- knowledge [28]. cosis mimicking a case of carcinoma of the max- From an epidemiological and pathogenetic illary sinus has been also described, as well as point of view, the inhalation of recreational the case of a chronic sinusal actinomycosis substances (cocaine and heroin), and the nasal which may masquerade as headache or other exposure to dust and mould (as in our case), subacute-chronic facial-brain disorders [18, 14]. seems to predispose to the development of seri- More specifically, an actinomycosis of the inter- ous ENT pathologic processes, like septal de- nal nose, of the nasal septum, the nasal wall, fects and ulcerations, superinfections, squa- and the nasal turbinates, remains an extremely mous cell carcinomas but also local tumors oth- rare occurrence, although an apparently novel er than adenocarcinoma, as well as a destruent species, named Actinomyces nasicola, has been midfacial osteomyelitis, which occurred in a recently isolated for the first time from a human chronic cocaine abuser [10, 11]. Intranasal nose, as a saprophytic organism of the local flo- nasal-septal lesions and ulcerations are a conse- ra [11, 13, 14, 19-22]. In the majority of the quence of the well known cocaine’s vasocon- sparsely reported cases, intranasal actinomyco- strictive properties, and the consequent de- sis presented with the appearance of a local crease of oxygen tension of intranasal tissue neoplasm [20]. Finally, an exceptional case of may greatly facilitate the growth of anaerobic primary cutaneous involvement of the external pathogens, including those belonging to the surface of the nose has been recently described rare human pathogens belonging to Actino- [23]. myces spp. [11]. A non-HIV-infected i.v. drug During the history of HIV pandemic, regardless abuser suffered from a rare, severe, and pro- of the availability of potent cART regimens, the longed (six month-long) episode of skin and prevalence of actinomycosis has remained low, soft-tissue caused by a concurrent despite the possible, even severe, impairment Actinomyces odontolyticus and two Prevotella of cellular and humoral immunity that accom- spp. organisms; a possible origin of this original pany HIV disease progression, so that actino- mixed flora from the oral cavity was suspected, mycosis has not been considered among oppor- since the patient referred licking his needle pri- tunistic infections possibly associated with ad- or to subcutaneous cocaine injection [29]. vanced HIV infection and AIDS [20]. Among Coming to the distinctive features of our report- patients with HIV disease and AIDS, very few ed case, in our patient the first diagnosis of cases of actinomycosis have been reported as rhinopharyngeal actinomycosis was oriented al- anecdotal observations or small case series, so by relevant epidemiological and behavioural which had a locally unfavourable outcome es- issues: the chronic cocaine and heroin inhalation pecially in the pre-cART era [20, 24-27]. Com- was recognized as a relevant risk factor for in- bined illnesses including actinomycosis plus tranasal ulcerative lesions which may support other infectious and non-infectious (i.e. fungal) superinfections, and the patient’s preferred hob- diseases have been occasionally reported, and by of searching mushrooms and truffles became the diagnostic and treatment difficulties have of real concern, due to the patient’s referred been repeatedly underlined [24, 25]. After the habit to smell and the repeated, unavoidable lo- introduction of cART, heterogeneous disease cal contact and intranasal aspiration of mould localizations of actinomycosis have been excep- and dust, which represent the known environ- tionally reported during the course of HIV in- mental reservoir of Actinomyces spp bacteria.

169 2008 Like other fastidious, anaerobe organism requir- the subsequent, extensive surgical intervention ing stringent conditions for microbiological cul- and removal of the entire mass, allowed to dis- ture and isolation, the diagnosis was posed on close the concurrent cancer disease. Despite an the characteristic appearance of granulomatous apparently correct administration of an ade- lesions (“sulfur” granules), at targeted intranasal quate antimicrobial chemotherapy, and the biopsy and related histopathology studies. The combined radiotherapy-chemotherapy, multi- underlying cancer lesions of the same region has ple brain secondary localizations led our patient not been initially suspected, since the first to a rapid death. fiberoptic rhinoscopy and biopsy did not allow In conclusion, our representative case report the recognition of malignant cells, while the ini- underlines that all health care professionals tial, combined CT and MRI imaging techniques who are involved in the follow-up of HIV-in- did not show neither osteolytic lesions, nor ab- fected patients should not overlook the possi- normalities of cartilage structures, as expected bility of multiple, overlapping, and not neces- during an invasive neoplastic process. sarily HIV-associated disease complications On the ground of a retrospective assessment of (like the extremely infrequent combination of the entire clinical follow-up and diagnostic- rhinopharyngeal actinomycosis plus squamo- management procedures, a bacterial (actinomy- cellular adenocarcinoma of the same rhinopha- cotic) superinfection of an underlying rhinopha- ryngeal site), in order to allow a rapid recogni- ryngeal carcinoma becomes a reasonable con- tion and a prompt and appropriate surgical and clusion, although to the best of our knowledge medical approach. The resort to extremely no literature evidences are retrievable in the in- stringent techniques for collecting and submit- ternational literature regarding associated ting tissue specimens for anaerobic culture and rhinopharyngeal actinomycosis plus squamous histopathological examinations are mandatory cell adenocarcinoma, among HIV-infected pa- for disclosing actinomycosis, while local inva- tients too, although both disorders share some sive procedures (biopsy and histopathology risk factors (i.e. exposure to toxic-oncogenic and studies), are needed to search an eventual, con- infectious inhalants like tobacco, cocaine, hero- current local malignancy, although an eventual in, and environmental bacteria and fungi). In superinfection may contribute to mimick and our subject, it remains extremely difficult to es- delay the recognition of an underlying cancer tablish whether actinomycosis overcome or not complication, like in our case. the underlying neoplastic manifestation, but while initial endoscopy-targeted biopsies ad- Key words: HIV infection, rhinopharyngeal actin- dressed towards an isolated actinomycosis, only omycosis, rhinopharyngeal adenocarcinoma.

SUMMARY

An extremely infrequent episode of nasopharyn- phy, magnetic resonance imaging, and fiberoptic geal actinomycosis associated with squamous ade- rhinoscopy with biopsy and histopathologic stud- nocarcinoma occurred in an HIV-infected male pa- ies, the final diagnosis of a combined dual infec- tient with a previous diagnosis of AIDS, treated tious-neoplastic pathology occurred only after a with combined antiretroviral therapy taken with demolishing surgical intervention and subsequent insufficient adherence, such that a satisfactory im- pathology studies. Despite proper antimicrobial mune system recovery (as expressed by a CD4+ therapy, and an associated radiotherapy and cyto- lymphocyte count persistently above 400 cells/µL), toxic chemotherapy schedule, rapid dissemination contrasted with a low-level persistence of de- of multiple secondary lesions to the brain rapidly tectable HIV viraemia, and enlarged genotypic re- led to our patient’s death. The imaging and sistance mutations. Interestingly, a number of local histopathological diagnostics of the dual illnesses and specific risk factors for both infectious and neo- of our HIV-infected patient, and its therapeutic and plastic disorders were recognized by healthcare outcome features, are presented and discussed on staff (tobacco smoke, long-term inhalatory sub- the basis of the evidence from the available litera- stance abuse, in particular cocaine, and semi-pro- ture. To the best of our knowledge, this is the first fessional mushroom-truffle hunting, including described case of actinomycosis associated with a evaluation by systematic smelling). Despite appro- local, underlying squamous cell adenocarcinoma of priate and timely diagnostic assessment carried out the same ear, nose, and throat district in either HIV- with repeated, combined computerized tomogra- infected or HIV-non-infected subjects.

170 2008 RIASSUNTO

Un episodio estremamente infrequente di associazione rinoscopia a fibre ottiche con relativi studi bioptici ed patologica tra actinomicosi ed adenocarcinoma squa- istopatologici, la diagnosi definitiva che evidenziava mocellulare del nasofaringe viene riportato in un pa- una duplice patologia di origine infettiva e neoplastica ziente di sesso maschile con pregressa diagnosi di si compiva soltanto dopo l’effettuazione di un interven- AIDS, trattato con terapie antiretrovirali di combina- to chirurgico demolitivo, ed i successivi studi patologi- zione assunte con aderenza insufficiente, cosicché un ci. Nonostante la somministrazione di una corretta te- soddisfacente recupero immunologico (testimoniato da rapia chemioantibiotica, ed un associato trattamento una conta di linfociti CD4+ stabilmente superiore a combinato di terapia radiante e di chemioterapia cito- 400 cellule/µL), contrastava con la persistenza di vire- tossica, una rapida disseminazione di multiple lesioni mia di HIV dimostrabile e con conseguenti, multiple secondarie a livello cerebrale portava rapidamente a mutazioni genotipiche di farmaco-resistenza. Di inte- morte il nostro paziente. La diagnostica per immagini e resse era il puntuale rilievo da parte dell’équipe assi- lo studio istopatologico della duplice patologia del no- stenziale di numerosi e specifici fattori di rischio locali stro paziente con concomitante infezione da HIV, in- per ambedue le patologie, infettiva e neoplastica (fumo sieme alle scelte terapeutiche e all’evoluzione clinica, di tabacco, uso prolungato di sostanze per via inalato- sono alla base della nostra presentazione, e della di- ria, in particolare di cocaina, ed un’attività semi-pro- scussione operata alla luce delle evidenze di letteratura fessionale di ricerca di funghi e tartufi, valutati siste- disponibili. Per quanto ci è fino ad oggi noto, non ri- maticamente anche con l’odorato). Sebbene fosse stata sultano finora descritti casi di associazione tra una ac- organizzata ed eseguita una completa e puntuale se- tinomicosi ed un locale, contemporaneo adenocarcino- quenza di appropriate valutazioni diagnostiche, con ma a cellule squamose dello stesso distretto ororinola- l’ausilio di ripetute, ed associate indagini di tomografia ringologico, sia in pazienti con infezione da HIV, sia in computerizzata, di risonanza magnetica nucleare, e di soggetti senza tale patologia concomitante.

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