Pediatric and Developmental Pathology 17, 478-481, 2014 DOI: 10.2350/14-05-1492-CR. 1 © 2014 Society fo r Pediatric Pathology

Actinomycotic Mastoiditis Complicated by Sigmoid Sinus Thrombosis and Labyrinthine Fistula C ecilia L ezcano, 1 J effrey P. Simons, 2 K athryn L. Colm an , 2 M M iguel R eyes- M ugica 1*

ichael

S. C ohen, 2 Philana L. Lin , 3

and

'Departm ent of Pathology, Children's Hospital o f Pittsburgh o f UPMC and University of Pittsburgh School o f Medicine, Pittsburgh, PA, USA d e p a rtm e n t o f Otolaryngology, Children's Hospital of Pittsburgh o f UPMC and University o f Pittsburgh School of Medicine, Pittsburgh, PA, USA d e p a rtm e n t of Pediatrics, Children's Hospital of Pittsburgh of UPMC and University o f Pittsburgh School o f Medicine, Pittsburgh, PA, USA

Received May 19, 2014; accepted August 14, 2014; published online August 18, 2014.

ABSTRACT

Actinomyces is a rare pathogen that can be the cause of infections in the digestive and urinary tracts, skin, genitalia, and lungs, which generally have an indolent clinical course. However, in some cases these can be locally destructive and become generalized infections. Actinomyces has been previously implicated in infections of the middle ear, nasopharynx, and sinuses, occasionally causing complications such as chronic mastoiditis. Here we describe the case of a 10-year-old-male presenting with nausea, vomiting, and headache who developed intracranial complications of actinomycotic mastoiditis. Key words: actinomycosis, labyrinthine fistula, mastoid­ itis, sigmoid sinus thrombosis

INTRODUCTION

Actinomycosis is a rare infection caused by a bacterium generally considered a human commensal: Actinomyces israelii [1]. However, in rare instances, other species, such as A odontolyticus, A turicensis, A viscosus, A bovis, A naeslundii, A meyeri, A europaeus, and A radingae, may also cause actinomycotic infections involving the digestive and urinary tracts, skin, genitalia, and lungs, as well as ear, nose, and throat [1-4], Although actinomycosis frequently follows an indo­ lent course, cases of locally aggressive as well as generalized disease, and even fatal outcomes, have been reported [5-8], The nonspecific nature of its symptoms, combined with difficulties in growing this bacterium in culture, can make diagnosis challenging. Therefore, it is important to become acquainted with unusual presenta­ *Corresponding author, e-mail: [email protected]

tions of actinomycosis. Here we describe a case of temporal bone actinomycosis presenting as a neck mass and otogenic Lemierre’s syndrome. CASE REPORT

A 10-year-old male with no previous otologic complaints presented with a 2-month history of intermittent nausea and vomiting associated with headache, fatigue, fever, and generalized malaise. He reported a 5-kg weight loss over 2 months. He denied hearing loss, vertigo, tinnitus, and otalgia. During several visits to his pediatrician and the emergency department, he was never found to have acute otitis media. Five days prior to presentation at our hospital, he developed left neck pain and swelling. His fevers became persistent, and he was admitted for further workup. Initial contrast-enhanced head and neck computed tomography (CT) revealed left internal jugular vein thrombosis and a left mastoid effusion. Contrastenhanced magnetic resonance imaging of the neck supported the diagnosis of left internal jugular vein thrombosis and also demonstrated enhancement of the left mastoid and middle ear. Additional imaging, including magnetic resonance venography and temporal bone CT, demonstrated left middle ear and mastoid opacification, erosion of the ossicles and lateral semicircular canal, and extension of the internal jugular vein thrombus to the sigmoid sinus to include a complete left sigmoid sinus thrombosis (Fig. 1). Audiometry demonstrated a left profound sensorineural hearing loss. The patient under­ went left mastoidectomy with decompression of the sigmoid sinus, repair of the lateral semicircular canal fistula, and a left myringotomy with tube placement. Histological analysis revealed small fragments of bone surrounded by fibrinous debris with Actinomyces colonies

F ig u re 1. C o m p u te d to m o g r a p h ic scan o f th e te m p o r a l bones

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showing Splendore-Hoeppli phenomenon. Periodic acidSchiff and the Brown and Brenn modification of the Gram stain enhanced the colonies of filamentous Gram­ positive bacteria clustered in sulfur granules. Morpholog­ ical examination of the microorganisms showed branch­ ing in predominantly acute angles (Fig. 2). Adjacent blood vessels showed no invasion by the microorganisms. Blood and tissue cultures were persistently negative. The infectious disease team recommended 6 weeks of intravenous meropenem followed by oral amoxicillin/ clavulanic acid for a total of 6 months. The patient was also placed on anticoagulation with enoxaparin for 6 months. Postoperatively, the patient improved clinically. He was discharged home with close follow-up. His nausea, fevers, headache, and neck mass have resolved. He has had a persistent left profound sensorineural hearing loss, likely secondary to the labyrinthine fistula. DISCUSSION Our patient had an erosive process of the temporal bone caused by Actinomyces, a rare but significant pathogen that may cause serious complications of chronic mastoid­ itis. Actinomyces (actin, from Greek oektIv- , aiczg = ray [9]) are mainly anaerobic (many are “ aerotolerant anaerobes,” but A israelii, the most frequent species, grows in anaerobic conditions), Gram-positive, acid fast­ negative, filamentous bacteria that branch predominantly in acute angles and show some resemblance to fungi, which explains its original misleading nomenclature [7,10], In tissue, colonies of Actinomyces frequently cluster together to form the typical and virtually pathognomonic sulfur granules and can present the Splendore-Hoppli phenomenon, which is the presence of intensely eosinophilic material, often in a starlike or radiated array, around clusters of microorganisms. The nature of this reaction has not been completely elucidated;

however, previous studies imply the presence of immune complexes, tissue debris, and fibrin, suggesting a local immune response process [11]. Actinomyces are present as normal flora in the oral cavity and pharynx, and their most frequent presentation is an indolent, suppurative process, most commonly in the cervicofacial region [7,12]. Transit through the Eustachian tube into the middle ear has been proposed as a mechanism for otomastoid actinomycosis [13]. Our patient had a complex and unusual presentation. The initial symptoms of nausea, vomiting, headache, malaise, and fever are vague and nonspecific, and generate a broad differential diagnosis. It was not until a tender neck mass developed that targeted studies leading to the diagnosis were performed. At that point it was clear that the patient had chronic otomastoiditis leading to a labyrinthine fistula, sigmoid sinus thrombo­ sis, and internal jugular vein thrombosis (otogenic Lemierre’s syndrome). The tissue biopsy taken at the time of surgery allowed for morphological identification of the underlying pathogen. Although isolation and culture of the causal microorganism from a clinical specimen comprise the gold standard for diagnosis [7], Actinomyces are difficult to culture, and bacterial confirmation is attained in fewer than 50% of cases with a clinicopathological diagnosis of actinomycosis [4], Therefore, recognition of the microorganism’s morpho­ logical features in tissue sections can be crucial for the diagnosis. To this end, the distinction between Actino­ myces and Nocardia, another Gram-positive branching filamentous bacteria that can present clinical manifesta­ tions similar to those seen in actinomycosis, is certainly challenging. However, the partially acid-fast character of Nocardia yields positive staining with the Fite-Faraco stain, while Actinomyces are negative, as they are non­ acid-fast bacteria. Additionally, identification of sulfur granules in tissue strongly favors Actinomyces over Nocardia infection [7]. Sulfur granules are classic findings in Actinomyces, and they range between 0.3 and 3 mm [14], making the latter visible with the naked eye. Although other species, including Nocardia, can form similar granules, according to Chandler and Connor [14], filaments of Actinomyces and related species are not even partially acid fast, which makes morphological identifica­ tion reliable and essentially a gold standard. However, indeterminate cases may require performance of molecular studies such as polymerase chain reaction and 16S rRNA gene sequencing to reach a definitive diagnosis [15], While an argument could be made that this is a case of cervical actinomycosis with jugular vein thrombosis, retrograde progression to the sigmoid sinus, and subse­ quent spread into the temporal bone, the clinical course with early headache, vomiting, and malaise, followed by late onset of a neck mass, strongly suggests the opposite route of progression. Already exceedingly rare [13,16,17], this particular case of temporal bone actinomycosis differs from previously described cases in that the patient did not present with most of the classic symptoms of A ctinomycotic M astoiditis

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Figure 2. A, N ecrotic debris and small bone fra g m e n ts associated w ith e ryth ro cyte extravasation su rro u n d in g some m astoid cells is observed (he m a toxylin-eosin [H&E], X100). B. The m id d le ear/m astoid e p ith e lia l lin in g is seen in th e u pp e r rig h t area associated w ith acute and chronic in fla m m a tio n in th e subjacent connective tissue (H&E, X200). C. A bacterial co lo ny w ith th e characteristic ra d ia tin g ("a c tin ic ") appearance o f s u lfu r granules (H&E, X600). D. In d ivid u a l fila m e n to u s bacteria, va ria b ly positive w ith a tissue m o d ific a tio n o f th e Gram te chn iqu e, are d em on strate d (B row n and Brenn, X1000).

otomastoiditis, including hearing loss, vertigo, otalgia, and otorrhea, although audiometry demonstrated a left profound sensorineural hearing loss. While invasion of the bony labyrinth, fallopian canal, and petrous apex have been previously reported [2,13,17], this pathogen typi­ cally progresses in an indolent and chronic manner [16]. This case presents a particularly destructive clinical course with its extension to the adjacent vasculature, comparable to 2 previously reported fatal cases of actinomycosis: one in which branches of the external carotid were involved from an initial tonsillar infection, and another with a protracted course of middle ear involvement complicated by venous sinus thrombosis, as in our case [6,8], Actinomycosis typically responds to long-term highdose penicillins. Surgical debridement is often necessary for complete resolution, as this anaerobic species can survive for long periods within poorly vascularized tissues, where antibiotics may not reach therapeutic concentrations [2,18]. Unfortunately, some long-tenn

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sequelae such as sensorineural hearing loss, as seen in our case, are not always reversible. This makes early detection, facilitated by a lower threshold for clinical suspicion, as well as prompt and appropriate treatment, crucial elements in complete recovery. REFERENCES 1. Sabbe LJ, Van De Merwe D, Schouls L, Bergmans A, Vaneechoutte M, Vandamme P. Clinical spectrum of infections due to the newly described Actinomyces species A. turicensis, A. radingae, and A. europaeus. J Clin Microbiol 1999;37:8-13. 2. Ono T, Yoshida Y, Izumaru S, Nakashima T. A case of nasopharyngeal actinomycosis leading to otitis media with effusion. Auris Nasus Larynx 2006;33:451-^t54. 3. Mansouri P, Farshi S, Khosravi A, Naraghi ZS. Primary cutaneous actinomycosis caused by Actinomyces bovis in a patient with common variable immunodeficiency. J Dermatol 2011 ;38;911— 915. 4. Mabeza GF, Macfarlane J. Pulmonary actinomycosis. Eur Respir J 2003;21:545-551. 5. Savidge RS, Davies DM. Generalized actinomycosis with possible cardiac involvement. Br Med J 1953;2(4828): 136.

6. Pezier TF, Kastrinidis N, Widmer GM, Huber GF, Probst R. Fatally invasive actinomycosis masquerading as a tonsillar carcinoma. Head Neck 2014;36:E129-E130. 7. Sullivan DC, Chapman SW. Bacteria that masquerade as fungi: actinomycosis/nocardia. Proc Am Thorac Soc 2010;7:216—

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8. Townrow V, Barrie HJ. Fatal Actinomyces infection of the middle ear. J Laryngol Otol 1945;60:329. 9. Old English Dictionary, “ actino-, comb. form” . New York: Oxford University Press. 10. Slack JM, Landffied S, Gerencser MA. Morphological, biochemical, and serological studies on 64 strains of Actinomyces israelii. J Bacteriol 1969;97:873-884. 11. Hussein MR. Mucocutaneous Splendore-Hoeppli phenomenon. J Cutan Pathol 2008;35:979-988. 12. Foster SV, Demmler GJ, Hawkins EP, Tillman JP. Pediatric cervicofacial actinomycosis. South Med J 1993;86:1147-1150.

13. Mehta D, Statham M, Choo D. Actinomycosis of the temporal bone with labyrinthine and facial nerve involvement. Laryngoscope 2007; 117:1999-2001. 14. Chandler FW, Connor DH. Actinomycosis. In: Connor DH, Chandler FW, Schwartz DA, Manz HJ, Lack EE, eds. Pathology of Infectious Diseases. 1, first ed. Stamford, CT: Appleton & Lange, 1997;391—396. 15. Fujita Y, Iikura M, Horio Y, Ohkusu K, Kobayashi N. Pulmonary Actinomyces graevenitzii infection presenting as organizing pneu­ monia diagnosed by PCR analysis. J Med Microbiol 2012;61(pt 8): 1156-1158. 16. Shelton C, Brackmann DE. Actinomycosis otitis media. Arch Otolaryngol Head Neck Surg 1988; 114:88-89. 17. Budenz CL, Tajudeen BA, Roehm PC. Actinomycosis of the temporal bone and brain: case report and review of the literature. Ann Otol Rhinol Laryngol 2010;119:313-318. 18. Sharkawy AA. Cervicofacial actinomycosis and mandibular osteo­ myelitis. Infect Dis Clin North Am 2007;21:543-556, viii.

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Actinomycotic mastoiditis complicated by sigmoid sinus thrombosis and labyrinthine fistula.

Actinomyces is a rare pathogen that can be the cause of infections in the digestive and urinary tracts, skin, genitalia, and lungs, which generally ha...
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