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Human Papilloma Virus Associated With Solitary Squamous Papilloma Complicated by Bronchiectasis and Bronchial Stenosis
exube ra nt host response to foreign antige n.f Both of these pati ents eve ntually did well with com bined surg ical and medical ther ap y. Surgery ofte n is avoided in med iastinal fibrosis ca used by histoplasmosis, du e to the obliteration of tissue plan es and the risk to other vital medi astinal struc tures." While th e decision to perform sur gery must be individualized , based on th ese two cases and th e pathologic characte ristics of blastom ycosis, th e surgical risk appear s to be acc eptable. Th e more im porta nt therapeutic implicati on of granulomatous med iastinitis ca used by blastom ycosis is that , unlik e histoplasmosis, it is ame nable to medi cal th er apy. Since blastom ycosis is cha rac te rized by an acu te polymorphonuclea r response and lar ge numbers of orga nisms, antifungal ther ap y can potentially eradica te th e inf ection and pr event further com promise of thor acic neurovascular structures. Th e pati ent with SVC syndrome had a relapse of blastom ycosis despit e prolonged high-dose ket oconazole th er ap y. It is difficult to assess the efficacy of ketoconazole in the case re ported here because th e patient pr em aturely discontinued his thera py on two occasions. In a recent review of blastom ycosis, it was recommended that ket oconazole repl ace amphotericin B as th erap y for com plian t pati ents with blastom ycosis, except in pati ents for whom th e disease is life-threatening.f Becau se of its risk to vital neu rovascular structures , we pr opose that extra pu lmonary thor acic disease also be tr eat ed with am phote ricin B. Itraconazole ther ap y may be an effec tive alte rna tive , given its success in th e tr eatment of pulmonar y and extrapulmonar y blastomycosis in a recent multicenter study." In summar y, we have descr ibed a case of blastom ycosis com prom ising the plexus brachialis. Th e pathologic cha racte ristics include a mi xed polymorphonuclea r and gra nulom at ous inflam ma tion, wit h large numbers of funga l organ isms. Persistent fun gal repli cati on is most likely responsible for this pathologic picture. Prolonged medi cal therapy is essential to pr event progressive intrathoracic disease or system ic relap se. Fi na lly, because of the utility for an tifunga l therapy suggested by its distin cti ve pathologic features, blastom ycosis should be conside red in th e differential diagnosis of extra pulmona ry thora cic disease. ACKNOWLEDGMENTS: The authors would like to thank Dr. Robert Collins for his review of the pathologic findings. R EFERENCES
1 Dines DE, Payne WE, Bernatz PE, Pairolero Pc. Mediastinal granuloma and fibrosing mediastinitis. Chest 1979; 75:320-24 2 Landay M], Rollins NK. Mediastinal histoplasmosisgranuloma: evaluation with CT. Radiology 1989; 172:657-59 3 Loyd ]E, Tillman BF, Atkinson JB, Des Prez RM. Mediastinal fibrosis complicating histoplasmosis. Medicine 1988; 67:295310
4 Mahajan V, Strimlan V, Van Ordstrand HS, Loop FD. Benign superior vena cava syndrome. Chest 1975; 68:32-5 5 Strimlan CV, Dines DE, Payne WS, Mediastinal granuloma. Mayo Clin Proc 1975; 50:702-05 6 Lagerstrom CF, Mitchell HG, Graham BS, Hammon ]H . Chronic fibrosing mediastinitis and superior vena caval obstruction from blastomycosis. AnnThorac Surg 1992;54:764-65 7 Parish ]M, Marschke RF, Dines DE, Lee RE. Etiologic considerationsin superior vena cavasyndrome. MayoClin Proc 1981; 56:407-13
8 Bradsher RW. Blastomycosis. Clin Infect Dis 1992; 14(suppl 1);582-90 9 Dismukes WE, Bradsher RW, Cloud GC, Kauffman CA, Chapman SW, George RB, et al. Itraconazole therapy for blastomycosis and histoplasmosis. Am ] Med 1992; 93:489-97
Human Papilloma Virus Associated With Solitary Squamous Papilloma Complicated by Bronchiectasis and Bronchial Stenosis* Rohit K. Katial, M.D.; Robert Ranlelt , M D .; and Warr en L. W hit lock, M.D., F.G.G.P.
A 28-year-old man presented with recurrent pneumonias for 6 yea rs. Chest radiograph and computed tomography showed localized bronchiectasis of the anterior segment of th e left upper lobe. Bronchoscopy showed bronchial sten osis with out an endobronchial le sion. After 6 weeks of antibiotic treatment, the patient had a recurrent pneumonia and underwent left upper lobectomy that sh owed a solitary squamous papilloma. In situ hybridization stud ies of the papilloma were reactive for human papilloma virus subtyp es 6/ll. (Chest 1994; 106:1887-89)
I HPV=human papillom a virus I Key words: bronchi al ste nosis; bron chi ectasis; human papillom a virus; in situ hybrid ization ; solita ry sq ua mo us papill om a papillomas are usuall y seen th rough T racheobronchial the bronchoscope and diagn osed b y br onchial biopsy
specimen. Th ey ca n have a vari ety of presentati ons, including cough, dy spn ea, hemoptysis, recurrent pn eumonias, and asthma. Th e availability of deoxyribonucleic acid (DNA) in sit u hybridization now allows classification of the viral etiology of th ese papill om as found in the tr acheobr onch ial tr ee. Th e following case illustrat es an unusual pr esentation of recurren t pneumonias, bronchia l stenosis, and bronchiectasis caused by a solita ry sq ua mo us papillom a not seen on chest com pu ted tom ography (CT) or b y bronchoscop y. C ASE R EPORT
A 28-year-old white man presented for evaluation of recurrent left upper lobe pneumonia. Over a 6-year period, he had seven pneumonias requiring antibiotic therapy. He complained of purulent sputum production, dyspnea, and several episodes of hemoptysis. The patient denied any history of decreased appetite, *From the Departments of Medicine (Dr. Katial), Pathology (Dr. Ranlett), and Pulmonary and Critical Care, Department of Medicine (Dr. Whitlock), Dwight David Eisenhower Army Medical Center, Augusta, Ga. Reprin t requests: Dr. W hit lock, D.D. Eisen hower Army Medical Genter, Fort Gordon , GA 30905-5650 CHEST I 106 1 6 I DECEMBER, 1994
1887
F IGL"lIE 1. Chest CT sca n sho wing br on chi ect asis of th e a nte rior seg me nt of the left upper lobe.
FIGUIIE 2. Bron ch oscopi c view of th e left upper lobe showing ste nosis of th e a nte rio r seg me nt wit ho ut ev ide nce of papill om a.
we ight loss, asthma, sin usitis, or tub er cul osis exposure. He also de nied tobacco or illicit drug use. Th e patient had no histor y of fore ign tra vel, a nd he was not taking a ny med icati ons. Pu lmo na ry exa m ination re vealed th at th e lun gs wer e clear to auscu lta tio n, a nd result s of th e rem ai nin g phys ical exam ination we re normal. Result s of labora tor y studies wer e unrem ark abl e. Human immu nodeficiency virus assay was negati ve. Pulmonar y function tests revealed a forced vita l ca pacity (FVC) of 3.89 L (9 1 percent of predicted ), forced expiratory volume in 1 s (FEV I) of 3.37 L (90 percen t of predicted) , a nd a FEV I to F VC rati o of 86 percent. Chest rad iograph re vealed a de nse left up per lobe infiltrate. The patient underwent bronchoscopy with bronc hoa lveolar lavage . Bronchial stenosis was fou nd in the an te rio r segme nt of the left upper lobe with thick mucopur ulen t secretio ns obstruc ting the dis ta l ai rway. Bacte rial cultures grew a n alpha-stre ptococcus species. Special stains for infectio us organisms, incl udi ng tu bercu losis and fungus, we re negat ive. Bron chi al bio psy specime n from the dis ta l a nterior seg me nt sho wed only respir at or y mu cosa with chronic inflam ma tion. The pati ent was pla ced on a 6-wee k regi me n of amoxic illin/clavulana te potassium a nd he had complete resoluti on of his symptoms. A chest CT sca n to evalua te th e dista l a irways showed only bron chi al ste nosis a nd bronchi ectasis (Fig I ). A rep eat ed bronchoscop y showed that th e secre tio ns had clear ed (F ig 2), and th er e was no e vide nce of a ma ss di sta l to th e ste nosis. Th e br onchoscope could not be passed through th e stenotic ope ni ng . Th e pati ent returned in 6 months with a sever e pneumonia requ irin g hospit ali zati on . After antibioti c th erapy, he underwent a resecti on of th e left upper lobe. Pat hologic study sho wed bron chi ect asis a nd a solita ry sq ua mo us papilloma . Dissecti on of the left upper lobe speci me n revealed occlusion of the anterio r segmenta l bronc hus by a fr iable white endobronchial mass measur ing 0.8 cm in d iameter. Bron chi di sta l to the mass were dil at ed an d filled w ith ten acious mucoid secretions. H istopathologic exa mi nation (Fig 3) of th e occlude d bronchus showed an exophytic papillom at ous lesion arising fro m the superificia l bronchia l mucosa composed of bland multila ye red non keratinizing squamous ep it he lium cove ri ng fibroco nnective tissue sta lks. Focally the surface epit helium exhibi ted par aker atosis and extensive infiltration by ac ute inflamma tory ce lls. Superficia l squamous ce lls exhibited pe rinu clear clea ri ng a nd en larged wrin kled nuclei co nsiste nt with koilocyt es. A tissue block was sen t to a laborat ory (Impa th Lab orat or ies, Ne w York ) for DNA ill situ hybridization using a biotiny late d doubl e-stranded DNA probe (D igene) to det ect hum an pa pilloma virus (H PV) DNA . /11 sit u hyridi zati on stud ies for H PV subty pes 6/ ll, 16/1 8, and 3 1/33 /35 re vealed nu clear posi tiv ity for HPV subty pes 6/ 11.
Th e pati ent has had no furth er co m plicatio ns. Becau se of th e potential for recurren ce and the associa tio n of HPV with m alignant a nd pre ma ligna nt lesions, he is under going bronchosco py every 6 months.
1888
OISC CSSIO ;o.:
Bronchi al papillom as have three distin ct clinical presenta tions: multiple papillomas, inflam ma tory polyps, or solita ry papill om as. I Multiple papillom as are th e most com mon an d occ ur in the lar yn x and lower respi rat ory tr act of child re n, althoug h they have been descr ibed in ad ults.f Th ey are associa ted with th e HP V and are th ought to be secon da ry to aspi ra tion of th e virus in utero or during parturition in a moth er inf ect ed with ge nita l warts.3A Inflammat or y papillom as arise in chronica lly inflam ed bronchi al mu cosa . They usuall y occ ur in conjunc tio n with chro nic ir rit ati on as seen with a foreign bod y, have an inflamm at or y cellul ar infiltrat e covered with respirator y ciliat ed epithe lium, and are not associa ted with th e HP V .5.6 Inflam matory polyps are included as part of th e di scussion
FIGVilE 3. Low-power view of th e exophytic endo bronc hia l mass within th e br onchus of th e a nterior seg me nt of the left upper lobe (he ma toxy lin-eos in, origina l magnificatio n X40). HPV Associated With Solitary Squamous Papilloma (Katial, Ranlett. Whitlock)
of bronchial papillomas because of confusion with " true" papillomas in th e ea rly literature.7•s The solita ry papillomas are th e rarest type. They usuall y present as an end ob ro nc hial mass in th e segm ental bronch i and may go undet ected for years.? Their highest prevalen ce is in m en in th eir 50s and 60s. Bar zo and colleagues'" obse rved onl y five cases of solita ry papillom as ove r 21 years and 15 ,000 bronch oscopi es. All th eir patients wer e m en , and th e younge st p ati ent th ey d escribed wa s 49 years old . Bron chi ectasis, fr eq uently m entioned as a compli cation of bronchial papillomas, was not observed in one series of seven cases of multiple papillomas wit h good radi ographic correlation.J! Our case d ocuments not onl y bron chiectasis b ut bron chial ste no sis th at may have be en secondary to th e recurrent pneumonias. Althou gh the multiple form has been associated with HPV sub ty pe s 6/11 , the exact pathophysiology for solitary sq uamous papilloma has not been deterrnined.P Our patient's DNA in situ hybridization stud ies of the resected papilloma demonstrated HPV sub ty pes 6/11, indicating HPV inf ection as th e cause of solita ry sq ua m ous papilloma of th e lung . This may represent delayed infection from birth, or more likely, it m ay be an acquired infection as an adult. Asp iration of th e virus as an adult would likel y ha ve a di fferent clinical presentation th an th at seen in the juvenil e form b ecau se of a m or e m ature immune system . W e specula te th at the virus is ac q ui re d through asp iration of in fec te d sec re ti ons in sexua lly ac tive young men. This ac counts for th e lat e clinical presen tation of solita ry squamous papillom a in older m en. In situ h ybridization is a technique that allo ws identificati on of p artic ular nucleic acid seq ue nces in tissues or cell s associ at ed with th e D N A " foo t-p ri nt" of a particular in fect ion. Nucle ic acid is visua lized by hybridization of labeled probes to target DN A in human tissue. The probes ca n b e d ouble-stranded DN A, single-strand ed D N A, or sing le-str anded ribonucleic acid (RN A) that can be lab eled with radioisot op e , biotin, fluor ochromes, enzy mes, or an tibodi es. The hybridization te chnique is accomplished b y e nzyme d igestion of tissue and denaturing cellular doublestra nded DNA. The homologous DNA or RNA probe then anneals with target D NA (HPV DNA in this case ) during th e hybridization process and is d et ected by the labeling technique . This process has cau sed revolutionary changes in th e conce p ts, classification , and pathogen esis of infectiou s di seases, genetic d isorders, and neopl asia b y ad d ing a new di agnostic technology.P Our case is unusual because of th e rar e occ urre n ce of th e solita ry form in a yo ung man and th e associa tion with HPV b y D N A in situ h ybridizati on stud ies. In our review of th e lit er ature, this is th e first case of solita ry bronchial papillom a not suspected after bron ch oscop y or chest CT, compli cat ed by b ro nc h ial ste nos is an d bronchiect asis, with evid en ce of HPV in fe ction diagnosed b y in situ D N A h ybridization . R EFERENCES
Drennan JM, Douglas AC. Solitary papilloma of a bronchus. J Clin Patho11965; 18:401-02 2 Glazer G, Webb WR. Laryngeal papillomatosis with pulmonary spread in a 69-year-old man. AJR 1979; 132:820-23
3 Borkowski W, Martin D, Lawrence HS. Juvenile laryngeal papillomatosis with pulmonary spread: regression following transfer factor therapy. Am J Dis Child 1984; 138:667-69 4 Cohen SR, Geller KA, Seltzer S. Papilloma of the larynx and tracheobronchial tree in children: a retrospective study. Ann Otol 1989; 80:497-503 5 Maxwell RJ, Gibbons JR. O'Hara MD. Solitary squamous papilloma of the bronchus. Thorax 1985; 40:68-71 6 Jackson DA, Hatch HB. Solitary benign squamous papilloma of the bronchus: report of two cases. Am Rev Respir Dis 1968; 97:699-704 7 Spencer H, Dail DH, Arneaud J. Non-invasive bronchial epithelial papillary tumors. Cancer 1980; 45:1486-97 8 Freant W. Sawyers JL. Benign bronchial polyps and papillomas. Ann Thorac Surg 1971; 11:460-67 9 Fraser RG. Pare JA, Pare PD, Fraser RS, Genereux GP. Neoplastic disease of the lung. In: Bralow L . ed. Diagnosis of diseasesof the chest. 3rd ed. Philadelphia: WB Saunders Co. 1989; 1502-05 10 Barzo P, Molnar L, Minik K. Bronchial papillomas of various origins. Chest 1987; 92:132-36 11 Kramer SS, Wehunt WD. Stocker JT, Kashima H. Pulmonar y manifestations of juvenile laryngotracheal papillomatosis. AJR 1985; 144:687-93 12 Mounts P, Kashima H. Association of human papilloma virus subtype and clinical course in respiratory papillomatosis. Laryngoscope 1984; 94:28-32 13 Wolfe HJ. DNA probes in diagnostic pathology. Am J Clin Pathol 1988; 90:340-44
Pulmonary Mucormycosis Presenting as an Endobronchial Lesion* Ahmad W. Husari, M .D.; W illiam A. j ensen , M .D.; Carl M. Kirsch, M .D.; An thon y C. Cam pagna, M.D. ; Frank T . Kagawa, M .D.; Kamal A. Ham ed , M.D .; Raymond L. Azzi, M.D .; and David A . Steven s, M .D.
A 56-year-old diabetic man presented with left upper lobe collapse and postobstructive pneumonitis. Fiberoptic bronchoscopy revealed an endobronchial mass obstructing the left mainstem bronchus. The lesion resembled a bronchial adenoma; however, cytologic and histologic examination revealed invasive mucormycosis, The patient was treated with intravenous amphotericin B followed by endoscopic laser su rgery that relieved the obstruction. (Chest 1994; 106:1889-91) Ke y words: bronchial adeno ma; endob ro nchial lesion ; mucorm ycosis; oppo rtu nistic in fection
M
ucorm ycosis is a n important op po rtun istic in fection ca use d b y fun gi th at belon g to the cla ss Zyg om ycet es. The disease wa s first reported by Paltaufl in 1885 *From the Divisions of Pulmonary and Critical Care Medicine and the Divisions of Infectious Disease, Stanford University School of Medicine and the Santa Clara Valley Medical Center, San Jose, Calif. Reprint requests: Dr. j ensen , Department of Medicine, Santa Clara Valley M edical Cent er, 751 South Bascom Avenue , San j ose, CA 95128 CHEST 1 106/ 61 DECEMBER . 1994
1889
1 Dines DE, Payne WE, Bernatz PE, Pairolero Pc. Mediastinal granuloma and fibrosing mediastinitis. Chest 1979; 75:320-24 2 Landay M], Rollins NK. Mediastinal histoplasmosisgranuloma: evaluation with CT. Radiology 1989; 172:657-59 3 Loyd ]E, Tillman BF, Atkinson JB, Des Prez RM. Mediastinal fibrosis complicating histoplasmosis. Medicine 1988; 67:295310
4 Mahajan V, Strimlan V, Van Ordstrand HS, Loop FD. Benign superior vena cava syndrome. Chest 1975; 68:32-5 5 Strimlan CV, Dines DE, Payne WS, Mediastinal granuloma. Mayo Clin Proc 1975; 50:702-05 6 Lagerstrom CF, Mitchell HG, Graham BS, Hammon ]H . Chronic fibrosing mediastinitis and superior vena caval obstruction from blastomycosis. AnnThorac Surg 1992;54:764-65 7 Parish ]M, Marschke RF, Dines DE, Lee RE. Etiologic considerationsin superior vena cavasyndrome. MayoClin Proc 1981; 56:407-13
8 Bradsher RW. Blastomycosis. Clin Infect Dis 1992; 14(suppl 1);582-90 9 Dismukes WE, Bradsher RW, Cloud GC, Kauffman CA, Chapman SW, George RB, et al. Itraconazole therapy for blastomycosis and histoplasmosis. Am ] Med 1992; 93:489-97
Human Papilloma Virus Associated With Solitary Squamous Papilloma Complicated by Bronchiectasis and Bronchial Stenosis* Rohit K. Katial, M.D.; Robert Ranlelt , M D .; and Warr en L. W hit lock, M.D., F.G.G.P.
A 28-year-old man presented with recurrent pneumonias for 6 yea rs. Chest radiograph and computed tomography showed localized bronchiectasis of the anterior segment of th e left upper lobe. Bronchoscopy showed bronchial sten osis with out an endobronchial le sion. After 6 weeks of antibiotic treatment, the patient had a recurrent pneumonia and underwent left upper lobectomy that sh owed a solitary squamous papilloma. In situ hybridization stud ies of the papilloma were reactive for human papilloma virus subtyp es 6/ll. (Chest 1994; 106:1887-89)
I HPV=human papillom a virus I Key words: bronchi al ste nosis; bron chi ectasis; human papillom a virus; in situ hybrid ization ; solita ry sq ua mo us papill om a papillomas are usuall y seen th rough T racheobronchial the bronchoscope and diagn osed b y br onchial biopsy
specimen. Th ey ca n have a vari ety of presentati ons, including cough, dy spn ea, hemoptysis, recurrent pn eumonias, and asthma. Th e availability of deoxyribonucleic acid (DNA) in sit u hybridization now allows classification of the viral etiology of th ese papill om as found in the tr acheobr onch ial tr ee. Th e following case illustrat es an unusual pr esentation of recurren t pneumonias, bronchia l stenosis, and bronchiectasis caused by a solita ry sq ua mo us papillom a not seen on chest com pu ted tom ography (CT) or b y bronchoscop y. C ASE R EPORT
A 28-year-old white man presented for evaluation of recurrent left upper lobe pneumonia. Over a 6-year period, he had seven pneumonias requiring antibiotic therapy. He complained of purulent sputum production, dyspnea, and several episodes of hemoptysis. The patient denied any history of decreased appetite, *From the Departments of Medicine (Dr. Katial), Pathology (Dr. Ranlett), and Pulmonary and Critical Care, Department of Medicine (Dr. Whitlock), Dwight David Eisenhower Army Medical Center, Augusta, Ga. Reprin t requests: Dr. W hit lock, D.D. Eisen hower Army Medical Genter, Fort Gordon , GA 30905-5650 CHEST I 106 1 6 I DECEMBER, 1994
1887
F IGL"lIE 1. Chest CT sca n sho wing br on chi ect asis of th e a nte rior seg me nt of the left upper lobe.
FIGUIIE 2. Bron ch oscopi c view of th e left upper lobe showing ste nosis of th e a nte rio r seg me nt wit ho ut ev ide nce of papill om a.
we ight loss, asthma, sin usitis, or tub er cul osis exposure. He also de nied tobacco or illicit drug use. Th e patient had no histor y of fore ign tra vel, a nd he was not taking a ny med icati ons. Pu lmo na ry exa m ination re vealed th at th e lun gs wer e clear to auscu lta tio n, a nd result s of th e rem ai nin g phys ical exam ination we re normal. Result s of labora tor y studies wer e unrem ark abl e. Human immu nodeficiency virus assay was negati ve. Pulmonar y function tests revealed a forced vita l ca pacity (FVC) of 3.89 L (9 1 percent of predicted ), forced expiratory volume in 1 s (FEV I) of 3.37 L (90 percen t of predicted) , a nd a FEV I to F VC rati o of 86 percent. Chest rad iograph re vealed a de nse left up per lobe infiltrate. The patient underwent bronchoscopy with bronc hoa lveolar lavage . Bronchial stenosis was fou nd in the an te rio r segme nt of the left upper lobe with thick mucopur ulen t secretio ns obstruc ting the dis ta l ai rway. Bacte rial cultures grew a n alpha-stre ptococcus species. Special stains for infectio us organisms, incl udi ng tu bercu losis and fungus, we re negat ive. Bron chi al bio psy specime n from the dis ta l a nterior seg me nt sho wed only respir at or y mu cosa with chronic inflam ma tion. The pati ent was pla ced on a 6-wee k regi me n of amoxic illin/clavulana te potassium a nd he had complete resoluti on of his symptoms. A chest CT sca n to evalua te th e dista l a irways showed only bron chi al ste nosis a nd bronchi ectasis (Fig I ). A rep eat ed bronchoscop y showed that th e secre tio ns had clear ed (F ig 2), and th er e was no e vide nce of a ma ss di sta l to th e ste nosis. Th e br onchoscope could not be passed through th e stenotic ope ni ng . Th e pati ent returned in 6 months with a sever e pneumonia requ irin g hospit ali zati on . After antibioti c th erapy, he underwent a resecti on of th e left upper lobe. Pat hologic study sho wed bron chi ect asis a nd a solita ry sq ua mo us papilloma . Dissecti on of the left upper lobe speci me n revealed occlusion of the anterio r segmenta l bronc hus by a fr iable white endobronchial mass measur ing 0.8 cm in d iameter. Bron chi di sta l to the mass were dil at ed an d filled w ith ten acious mucoid secretions. H istopathologic exa mi nation (Fig 3) of th e occlude d bronchus showed an exophytic papillom at ous lesion arising fro m the superificia l bronchia l mucosa composed of bland multila ye red non keratinizing squamous ep it he lium cove ri ng fibroco nnective tissue sta lks. Focally the surface epit helium exhibi ted par aker atosis and extensive infiltration by ac ute inflamma tory ce lls. Superficia l squamous ce lls exhibited pe rinu clear clea ri ng a nd en larged wrin kled nuclei co nsiste nt with koilocyt es. A tissue block was sen t to a laborat ory (Impa th Lab orat or ies, Ne w York ) for DNA ill situ hybridization using a biotiny late d doubl e-stranded DNA probe (D igene) to det ect hum an pa pilloma virus (H PV) DNA . /11 sit u hyridi zati on stud ies for H PV subty pes 6/ ll, 16/1 8, and 3 1/33 /35 re vealed nu clear posi tiv ity for HPV subty pes 6/ 11.
Th e pati ent has had no furth er co m plicatio ns. Becau se of th e potential for recurren ce and the associa tio n of HPV with m alignant a nd pre ma ligna nt lesions, he is under going bronchosco py every 6 months.
1888
OISC CSSIO ;o.:
Bronchi al papillom as have three distin ct clinical presenta tions: multiple papillomas, inflam ma tory polyps, or solita ry papill om as. I Multiple papillom as are th e most com mon an d occ ur in the lar yn x and lower respi rat ory tr act of child re n, althoug h they have been descr ibed in ad ults.f Th ey are associa ted with th e HP V and are th ought to be secon da ry to aspi ra tion of th e virus in utero or during parturition in a moth er inf ect ed with ge nita l warts.3A Inflammat or y papillom as arise in chronica lly inflam ed bronchi al mu cosa . They usuall y occ ur in conjunc tio n with chro nic ir rit ati on as seen with a foreign bod y, have an inflamm at or y cellul ar infiltrat e covered with respirator y ciliat ed epithe lium, and are not associa ted with th e HP V .5.6 Inflam matory polyps are included as part of th e di scussion
FIGVilE 3. Low-power view of th e exophytic endo bronc hia l mass within th e br onchus of th e a nterior seg me nt of the left upper lobe (he ma toxy lin-eos in, origina l magnificatio n X40). HPV Associated With Solitary Squamous Papilloma (Katial, Ranlett. Whitlock)
of bronchial papillomas because of confusion with " true" papillomas in th e ea rly literature.7•s The solita ry papillomas are th e rarest type. They usuall y present as an end ob ro nc hial mass in th e segm ental bronch i and may go undet ected for years.? Their highest prevalen ce is in m en in th eir 50s and 60s. Bar zo and colleagues'" obse rved onl y five cases of solita ry papillom as ove r 21 years and 15 ,000 bronch oscopi es. All th eir patients wer e m en , and th e younge st p ati ent th ey d escribed wa s 49 years old . Bron chi ectasis, fr eq uently m entioned as a compli cation of bronchial papillomas, was not observed in one series of seven cases of multiple papillomas wit h good radi ographic correlation.J! Our case d ocuments not onl y bron chiectasis b ut bron chial ste no sis th at may have be en secondary to th e recurrent pneumonias. Althou gh the multiple form has been associated with HPV sub ty pe s 6/11 , the exact pathophysiology for solitary sq uamous papilloma has not been deterrnined.P Our patient's DNA in situ hybridization stud ies of the resected papilloma demonstrated HPV sub ty pes 6/11, indicating HPV inf ection as th e cause of solita ry sq ua m ous papilloma of th e lung . This may represent delayed infection from birth, or more likely, it m ay be an acquired infection as an adult. Asp iration of th e virus as an adult would likel y ha ve a di fferent clinical presentation th an th at seen in the juvenil e form b ecau se of a m or e m ature immune system . W e specula te th at the virus is ac q ui re d through asp iration of in fec te d sec re ti ons in sexua lly ac tive young men. This ac counts for th e lat e clinical presen tation of solita ry squamous papillom a in older m en. In situ h ybridization is a technique that allo ws identificati on of p artic ular nucleic acid seq ue nces in tissues or cell s associ at ed with th e D N A " foo t-p ri nt" of a particular in fect ion. Nucle ic acid is visua lized by hybridization of labeled probes to target DN A in human tissue. The probes ca n b e d ouble-stranded DN A, single-strand ed D N A, or sing le-str anded ribonucleic acid (RN A) that can be lab eled with radioisot op e , biotin, fluor ochromes, enzy mes, or an tibodi es. The hybridization te chnique is accomplished b y e nzyme d igestion of tissue and denaturing cellular doublestra nded DNA. The homologous DNA or RNA probe then anneals with target D NA (HPV DNA in this case ) during th e hybridization process and is d et ected by the labeling technique . This process has cau sed revolutionary changes in th e conce p ts, classification , and pathogen esis of infectiou s di seases, genetic d isorders, and neopl asia b y ad d ing a new di agnostic technology.P Our case is unusual because of th e rar e occ urre n ce of th e solita ry form in a yo ung man and th e associa tion with HPV b y D N A in situ h ybridizati on stud ies. In our review of th e lit er ature, this is th e first case of solita ry bronchial papillom a not suspected after bron ch oscop y or chest CT, compli cat ed by b ro nc h ial ste nos is an d bronchiect asis, with evid en ce of HPV in fe ction diagnosed b y in situ D N A h ybridization . R EFERENCES
Drennan JM, Douglas AC. Solitary papilloma of a bronchus. J Clin Patho11965; 18:401-02 2 Glazer G, Webb WR. Laryngeal papillomatosis with pulmonary spread in a 69-year-old man. AJR 1979; 132:820-23
3 Borkowski W, Martin D, Lawrence HS. Juvenile laryngeal papillomatosis with pulmonary spread: regression following transfer factor therapy. Am J Dis Child 1984; 138:667-69 4 Cohen SR, Geller KA, Seltzer S. Papilloma of the larynx and tracheobronchial tree in children: a retrospective study. Ann Otol 1989; 80:497-503 5 Maxwell RJ, Gibbons JR. O'Hara MD. Solitary squamous papilloma of the bronchus. Thorax 1985; 40:68-71 6 Jackson DA, Hatch HB. Solitary benign squamous papilloma of the bronchus: report of two cases. Am Rev Respir Dis 1968; 97:699-704 7 Spencer H, Dail DH, Arneaud J. Non-invasive bronchial epithelial papillary tumors. Cancer 1980; 45:1486-97 8 Freant W. Sawyers JL. Benign bronchial polyps and papillomas. Ann Thorac Surg 1971; 11:460-67 9 Fraser RG. Pare JA, Pare PD, Fraser RS, Genereux GP. Neoplastic disease of the lung. In: Bralow L . ed. Diagnosis of diseasesof the chest. 3rd ed. Philadelphia: WB Saunders Co. 1989; 1502-05 10 Barzo P, Molnar L, Minik K. Bronchial papillomas of various origins. Chest 1987; 92:132-36 11 Kramer SS, Wehunt WD. Stocker JT, Kashima H. Pulmonar y manifestations of juvenile laryngotracheal papillomatosis. AJR 1985; 144:687-93 12 Mounts P, Kashima H. Association of human papilloma virus subtype and clinical course in respiratory papillomatosis. Laryngoscope 1984; 94:28-32 13 Wolfe HJ. DNA probes in diagnostic pathology. Am J Clin Pathol 1988; 90:340-44
Pulmonary Mucormycosis Presenting as an Endobronchial Lesion* Ahmad W. Husari, M .D.; W illiam A. j ensen , M .D.; Carl M. Kirsch, M .D.; An thon y C. Cam pagna, M.D. ; Frank T . Kagawa, M .D.; Kamal A. Ham ed , M.D .; Raymond L. Azzi, M.D .; and David A . Steven s, M .D.
A 56-year-old diabetic man presented with left upper lobe collapse and postobstructive pneumonitis. Fiberoptic bronchoscopy revealed an endobronchial mass obstructing the left mainstem bronchus. The lesion resembled a bronchial adenoma; however, cytologic and histologic examination revealed invasive mucormycosis, The patient was treated with intravenous amphotericin B followed by endoscopic laser su rgery that relieved the obstruction. (Chest 1994; 106:1889-91) Ke y words: bronchial adeno ma; endob ro nchial lesion ; mucorm ycosis; oppo rtu nistic in fection
M
ucorm ycosis is a n important op po rtun istic in fection ca use d b y fun gi th at belon g to the cla ss Zyg om ycet es. The disease wa s first reported by Paltaufl in 1885 *From the Divisions of Pulmonary and Critical Care Medicine and the Divisions of Infectious Disease, Stanford University School of Medicine and the Santa Clara Valley Medical Center, San Jose, Calif. Reprint requests: Dr. j ensen , Department of Medicine, Santa Clara Valley M edical Cent er, 751 South Bascom Avenue , San j ose, CA 95128 CHEST 1 106/ 61 DECEMBER . 1994
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