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The new england journal of medicine

Case Records of the Massachusetts General Hospital

Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor Nancy Lee Harris, M.D., Editor Jo-Anne O. Shepard, M.D., Associate Editor Alice M. Cort, M.D., Associate Editor Sally H. Ebeling, Assistant Editor Emily K. McDonald, Assistant Editor

Case 25-2015: An 8-Year-Old Girl with a Chest-Wall Mass and a

Samuel M. Moskowitz, M.D., Randheer Shailam, M.D., and Eugene J. Mark, M.D.

Presentation of Case

Dr. Jessica M. Rosenthal (Pediatrics): An 8-year-old girl who had required long-term From the Departments of Pediatrics tracheostomy because of airway stenosis caused by an injury in infancy was admitted (S.M.M.), Radiology (R.S.), and Patholo- gy (E.J.M.), Massachusetts General Hos- to this hospital because of a chest-wall mass and a large pleural effusion. pital; and the Departments of Pediatrics The patient was born in China. At 7 months of age, she underwent emergency (S.M.M.), Radiology (R.S.), and Pathology tracheostomy after a caustic injury from either ingestion or inhalation. At 2.5 years (E.J.M.), Harvard Medical School — both in Boston. of age, she was adopted by an American family and moved to the United States. Her adoptive parents noted that she had stridor and snoring, and her pediatrician N Engl J Med 2015;373:657-67. DOI: 10.1056/NEJMcpc1400836 referred her to an otolaryngologist at the Massachusetts Eye and Ear Infirmary (MEEI) Copyright © 2015 Massachusetts Medical Society. at 2 years 10 months of age. On examination, the nasopharynx was completely ob- structed; there was fusion of the posterior tongue and hard palate and of the hard palate and , with a narrow opening in the oropharynx. The supraglottic pas- sage was normal beyond the stenosis; the subglottic airway was not evaluated. A tracheostomy was performed, and the left nasal choanal obstruction was opened with a laser. Repeat bronchoscopy revealed that the and subglottic were normal. On two occasions, esophagogastroduodenoscopy revealed no evidence of gastroesophageal reflux. The tracheostomy tube was removed when the patient was 5.5 years of age; there was a residual tracheal–cutaneous . When she was 7.5 years of age (7 months before this admission), another trache- ostomy was performed because of worsening oropharyngeal stenosis that pre- cluded intubation and because of concern about possible obstruction. The patient had been in her usual state of health until approximately 6.5 weeks before this admission; during a 10-day period, her mother noted recurrent blood- tinged sputum in the tracheostomy tube, and an episode of bleeding at the trache- ostomy site occurred at school. The patient was seen in the emergency department of the MEEI, where a flexible tracheoscopy, which was performed at the bedside after removal of the tracheostomy tube, revealed no exposed blood vessels or granulation tissue in the trachea or stoma. A showed consolida- tion in the right lower lobe, which was thought to be due to aspiration, pneumo- nia, or . Gram’s staining of the sputum showed abundant neutrophils, abundant gram-positive cocci in pairs and a few chains, abundant gram-negative diplococci, a few gram-positive rods, and a few thin gram-negative rods. Culture

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of the sputum from the tracheostomy tube grew and siblings; she was physically active, did well in methicillin-susceptible , Morax- school, and was able to breathe, speak, and eat ella catarrhalis, Haemophilus influenzae, and Strepto- normally, with the tracheostomy tube capped while coccus pneumoniae. The patient remained afebrile, she was awake. She lived with two dogs and a cat, and no agents were administered. She and the mother smoked outside the home; she was admitted overnight for observation and dis- had not recently traveled or had contact with ill charged home the next day (5 weeks before this persons. admission). She had one more episode of blood- On examination, the temperature was 37.0°C, tinged sputum thereafter. the blood pressure 102/68 mm Hg, the pulse During the 2 weeks before this admission, the 135 beats per minute, the respiratory rate 16 to oxygen saturation, which was obtained during 30 breaths per minute, and the oxygen saturation continuous overnight monitoring for sleep apnea, 95% while the patient was breathing ambient air. fell to approximately 85% (from the usual level The oropharynx was clear, without erythema or of approximately 95%) for prolonged periods. focal lesions. The was supple, and the tra- Examination at school revealed decreased breath cheostomy site was clean and dry, with an under- sounds at the base of the right . One day be- lying small cavity. Lymphadenopathy (with nodes fore this admission, while the patient was being measuring up to 1 cm in diameter) in the right bathed, her mother noticed that her chest was anterior cervical chain and a mildly tender right asymmetric, with the right nipple appearing lower axillary lymph node (approximately 1 cm in di- than the left, and that blood vessels were prom- ameter) were present. There were decreased inent on the right side of the chest. breath sounds at the base of the right lung. At the pediatrician’s office the next day, the There was a bulging area (4 cm by 7 cm) on the patient described a recent episode of discomfort right lateral chest wall, which was tender on in her chest that occurred while she was being palpation and had no fluctuance or overlying skin hugged. There was no history of respiratory dis- changes. The hematocrit, red-cell indexes, and tress, fevers, or . On examination, she was anion gap were normal, as were blood levels of tearful and hesitant. The temperature was 36.1°C, calcium, magnesium, glucose, albumin, amylase, and a tracheostomy tube was in place. The right lipase, uric acid, and lactic dehydrogenase and lateral chest wall was more prominent than the results of renal- and liver-function tests; other left, had no crepitus, and was tender to touch. test results are shown in Table 1. Breath sounds were normal on the left side and Dr. Randheer Shailam: A frontal chest radiograph diminished on the right. The right upper quad- that had been obtained 7 months before this rant of the abdomen was diffusely tender, and the admission showed a tracheostomy tube, clear remainder of the examination was normal. The , and no pleural effusion. Frontal, lateral, patient was referred to another hospital for chest and bilateral decubitus chest radiographs that radiography, which revealed a large pleural effu- were obtained on the day of admission (Fig. 1) sion on the right side, with underlying pneumo- showed dense air-space opacification in the right nia. The patient was referred to the emergency lower lung zone, obscuring the right hemidia- department of this hospital. phragm and right cardiac border, as well as a large The patient had sleep apnea and a history of pleural effusion on the right side that tracked dental caries that necessitated the extraction of along the lateral chest wall, with evidence of locu- several deciduous teeth between 5 and 7 years lation. The left lung and pleural space were clear. of age. Immunizations, including the 7-valent Computed tomography (CT) of the chest, per- pneumococcal conjugate vaccine (PCV7), were formed on the same day after the administration current; she had reportedly received the bacille of contrast material (Fig. 2), revealed asymmetry Calmette–Guérin (BCG) vaccine at 1 month of of the chest wall that was due to multiple hetero- age. A purified protein derivative (PPD) skin test geneous soft-tissue masses and thickening of the was negative on her arrival in the United States. of the right chest wall. Consolidation She took no medications and had no known aller- was present in the right lower lobe and portions gies. She lived at home with her adoptive parents of the right middle lobe. Areas of low attenua-

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tion in the right lower lobe were suggestive of de- Table 1. Laboratory Data.* creased perfusion and possible necrosis. A large loculated pleural effusion, irregularly shaped pa- Reference Range, On Admission, renchymal nodules in the right upper lobe, promi- Variable Age-Adjusted† This Hospital nent enhancing ipsilateral axillary lymph nodes, Hemoglobin (g/dl) 11.5–15.5 11.2 and subtle periosteal elevation of the medial as- White-cell count (per mm3) 4500–13,500 11,500 pect of the right eighth rib were also present. Dr. Rosenthal: The patient was admitted to the Differential count (%) pediatric intensive care unit. The temperature rose Neutrophils 33–59 73 to 38.7°C, and acetaminophen was administered, Lymphocytes 33–50 20 with improvement. On the second hospital day, a diagnostic pro- Monocytes 4–11 5 cedure was performed. Eosinophils 0–8 2 Platelet count (per mm3) 150,000–450,000 891,000 Sodium (mmol/liter) 135–145 134 Dr. Samuel M. Moskowitz: This 8-year-old girl had Potassium (mmol/liter) 3.4–4.8 3.8 had a caustic exposure during infancy that resulted Chloride (mmol/liter) 100–108 96 in upper- and tracheostomy Carbon dioxide (mmol/liter) 23.0–31.9 25.1 dependence. I suspect that her airway injury may have caused mild dysphagia, with an increased risk Protein (g/dl) of tracheal aspiration. She had a history of poor Total 6.0–8.3 8.5 oral hygiene. Her immunizations included PCV7 Globulin 2.3–4.1 5.0 and BCG, and a PPD skin test was negative after she immigrated to the United States. Six weeks Phosphorus (mg/dl) 4.5–5.5 4.0 before this admission, bacterial with S. C-reactive protein (mg/liter) <8.0 for inflammation 217.2 aureus, S. pneumoniae, and H. inf luenzae developed, and focal opacification of the right lower lobe * To convert the values for phosphorus to millimoles per liter, multiply by 0.3229. was noted. Bacterial tracheobronchitis and pneu- † Reference values are affected by many variables, including the patient popula- monia are common in children who have under- tion and the laboratory methods used. The ranges used at Massachusetts gone tracheostomy, with an annual incidence of General Hospital are age-adjusted for patients who are not pregnant and do 1 not have medical conditions that could affect the results. They may therefore up to 88%. The tracheitis abated spontaneously, not be appropriate for all patients. without antibiotic treatment, whereas the lobar process progressed and was accompanied by hy- poxemia, chest tenderness, decreased breath nosis includes trauma, , inflammatory sounds, and pleural effusion but no fever. and infectious processes, or a combination of On presentation, the patient had tachypnea, these causes (Table 2). Before the results of im- prominence and tenderness of the right lateral aging studies are available to rule in or rule out chest wall, and a tender right axillary lymph node. specific causes, the mass could represent a her- Laboratory test results showed elevated levels of niated right lung, a benign or malignant tumor, acute-phase reactants, such as thrombocytosis a sterile collection of inflammatory cells, or an and hyperglobulinemia. Imaging studies of the abscess. chest revealed opacification in the right lower lung zone, a loculated effusion, and an irregular Chest-Wall Trauma chest-wall mass, with regional lymph-node en- Traumatic disruption of the skeletal compo- hancement and minimal bony changes. nents of the chest wall can result in flail chest, The chest-wall mass is the most worrisome with paradoxical chest-wall motion and com- clinical feature of this child’s presentation. An promised gas exchange; these findings were acquired chest-wall deformity or mass can origi- not present in this child. Lung herniation is an nate in bone or soft tissue; the differential diag- uncommon chest-wall deformity that causes

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A B

*

*

C D

Figure 1. Chest Radiographs. Radiographs of the chest were obtained on admission. Frontal and lateral chest radiographs (Panels A and B, re- spectively) show air-space opacification in the right lower lung zone (asterisks) and a large right pleural effusion (arrows). Decubitus chest radiographs (Panel C [right side down] and Panel D [left side down]) show that pleural fluid on the right side is not freely layering (arrows).

dyspnea, pain, and a bulge that varies with the out a history of recent trauma, the diagnoses of respiratory cycle. It usually results from trauma hematoma and ruptured hemidiaphragm are also but can also be congenital, arise spontaneously unlikely. after a coughing paroxysm, or occur in patients with neoplastic, inflammatory, or infectious dis- Benign and Malignant Tumors orders of the chest wall.2 In this child, exami- of the Chest Wall nation and imaging studies did not reveal the Various benign and malignant tumors can arise characteristic bulge of a herniated lung. With- from the bones of the chest wall (Table 2). How-

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A B

C D *

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E F *

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Figure 2. CT Scans of the Chest. CT scans of the chest were obtained on admission, after the intravenous administration of contrast material. Panel A shows asymmetry of the chest wall, thickening of the soft tissue of the right chest wall (arrowheads), and multiple heterogeneous soft-tissue masses (arrows). Panels B and C show irregularly shaped parenchymal nodules in the right upper lobe (arrows). Panel D shows consolidation in the right lower lobe (arrow) and portions of the right middle lobe, areas of low attenuation in the right lower lobe that suggest decreased perfusion and possible necrosis (arrowheads), and a large loculated pleural effusion (asterisks). Panel E also shows the large loculated pleural effu- sion (asterisks), as well as a prominent enhancing axillary lymph node (arrow). Panel F shows subtle periosteal ele- vation of the medial aspect of the right eighth rib (arrow).

ever, in this case, chest CT revealed only a mini- this case. Other benign tumors originating in soft mal rib lesion, and thus a bony tumor is unlikely. tissue, such as , are more common in Some benign tumors that occur in children, such adults than in children. Peripheral-nerve tumors as lymphangioma (cystic hygroma) or hemangio- can be associated with effusion and pleural nod- ma, arise in the soft tissue of the chest wall and ules but would be more likely to occur in a patient are generally confined to it, without the pleural with known neurofibromatosis. Desmoid tumor, and pulmonary components that were seen in a histologically benign that can be

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Table 2. Differential Diagnosis of Acquired Chest-Wall Deformity or Mass in a Child.

Diagnosis Originates in or Affects Bone Originates in or Affects Soft Tissue

Trauma Flail chest Lung herniation, hematoma, ruptured hemidiaphragm Benign tumor Eosinophilic granuloma (Langerhans’-cell histiocyto- Lymphangioma (cystic hygroma), hemangioma, periph- sis), osteochondroma (exostosis), chondroma, eral-nerve tumor (neurofibroma, plexiform neurofi- chondroblastoma, fibrous dysplasia, osteoid broma, schwannoma), , fibromatosis (des- osteoma, osteoblastoma, mesenchymal ham- moid tumor), lipoma, benign cystic , artoma inflammatory myofibroblastic tumor Malignant neoplasm Osteosarcoma of the rib, chondrosarcoma of the rib, , other (neurofibrosarco- primitive neuroectodermal tumor (Ewing’s sar- ma, , , angiosarcoma, coma, Askin’s tumor), multiple myeloma, metas- ), pleuropulmonary , lympho- tasis ma, malignant fibrous , Inflammatory process Hyperostosis, SAPHO syndrome (synovitis, acne, Sebaceous pustulosis, hyperostosis, osteitis), chronic recur- rent multifocal osteomyelitis (nonpurulent in- flammation of bone), Friedrich’s disease (aseptic necrosis of the sternoclavicular joint) Infectious process Osteomyelitis (tuberculosis, actinomycosis), septic Abscess, phlegmon, cellulitis, necessitatis arthritis

locally invasive, is more likely to occur in the ever, because of the consequences of missing a shoulder region than in the anterolateral chest.3 malignant neoplasm, these lesions deserve con- Benign mesothelioma is rare in children and sideration. In children, rhabdomyosarcoma is the usually confined to the pleural space. most common malignant tumor arising in the Patients with an inflammatory myofibroblas- soft tissue of the chest wall, but the associated tic tumor can present with a soft-tissue mass of chest CT would typically reveal a discrete mass,4 the chest wall. It arises from lung parenchyma and which is unlike the finding in this child. Other can extend into the chest wall, with localized mass soft-tissue sarcomas are relatively rare in children. effect.4 These lesions, which are the most com- Pleuropulmonary blastoma arises from the pleu- mon lung tumors in children, are typically benign ra or lung and can invade the chest wall, but it but can occasionally undergo malignant trans- usually occurs in children 5 years of age or young- formation. They are typically associated with dys- er. Malignant fibrous histiocytoma is usually pnea, cough, hemoptysis, and fever. Laboratory confined to the chest wall and is more common evaluation may reveal iron-deficiency anemia, in elderly persons than in children. thrombocytosis, and hypergammaglobulinemia. in the thorax typically arise in However, chest-wall invasion is inconsistent and the and can extend into the anterior generally occurs no sooner than 12 to 18 months chest wall, and thus a locally invasive after the onset of symptoms, pleural effusions are needs to be considered in this case. Patients with uncommon, and lymphadenopathy is rare. Asso- thoracic lymphoma typically present with chest ciated chest CT reveals a varying nonspecific pat- pain, dyspnea, and lymphadenopathy, sometimes tern, with heterogeneous enhancement and at- without fever. Early-stage Hodgkin’s or non-Hodg- tenuation.5 The laboratory test results and imaging kin’s lymphoma that arises in the mediastinum findings in this patient were suggestive of an in- can invade the lung parenchyma and chest wall, flammatory myofibroblastic tumor, but her course but this invasion usually is contiguous with a was unusually rapid for this lesion and she did not tumor in the anterior mediastinum and does not have several of the usual . involve the lower lateral chest (the location of This child did not have persistent systemic the chest-wall lesion seen in this child).6,7 In ad- symptoms suggestive of a malignant tumor; how- dition, lymphomatous chest-wall invasion usu-

662 n engl j med 373;7 nejm.org August 13, 2015 The New England Journal of Medicine Downloaded from nejm.org at The University Of Illinois on March 10, 2017. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital ally develops more slowly than did the process art, have been observed from time to time by the in this child. surgeons, and their opening constitutes what is In summary, a neoplastic process cannot be commonly called the empyema of necessity. This ruled out in this case, but an inflammatory or case is also very rare; my friend Mr. Recamier infectious process is more likely. told me that he has observed twice; I have en- countered it but once.”8 Inflammatory and Infectious Processes The patient in Laennec’s case is said to have of the Chest Wall been a 12-year-old boy. In 1869, William Moore Primary inflammation of bone, such as that seen described empyema necessitatis in a 10-year-old with hyperostosis or chronic recurrent multifocal girl.9 The publication of only a few relevant case osteomyelitis, can cause a chest-wall mass. Vari- reports since the 19th century indicates that this ous pathogens can cause osteomyelitis or septic condition remains extremely rare in children; arthritis with localized chest-wall swelling and nonetheless, I believe that this child had empy- induration. However, the localization and imag- ema necessitatis. ing findings in this child were not consistent Empyema necessitatis was more common in with an osseous lesion. the era before . At that time, it was as- Patients with a sebaceous cyst can present sociated with an overall mortality of approximately with a soft-tissue mass, but it would remain 66%; the most common pathogens were Myco- confined to the chest wall and would not invade bacterium tuberculosis (mortality, 87%) and S. pneu- the pleura or lung. Soft-tissue infections of the moniae (mortality, 28%). Since antibiotics have been chest wall can be manifested by a solitary ab- in use, cases of empyema necessitatis are rarely scess or cellulitis, with associated inflammation fatal, and actinomyces species are a more common of adjacent tissues. However, several findings in cause than is S. pneumoniae. Less common patho- this child were consistent with an infection origi- gens include S. aureus, S. milleri, Fusobacterium nuclea- nating in the chest cavity and extending into the tum, M. avium, M. intracellulare, Burkholderia cepacia, chest wall. blastomyces species, and Nocardia asteroides.10 Given this child’s history of BCG immuniza- Empyema Necessitatis tion and the negative PPD skin test, tuberculosis The clinical and radiographic features seen in is unlikely. Because a culture of tracheal secretions this case are most consistent with empyema ne- was positive for S. pneumoniae, it would seem to be cessitatis, a process characterized by extension of a prime suspect; it is found in pleural fluid in pleural empyema into the chest wall. This condi- approximately 50% of children with uncompli- tion was first described by Gullan de Baillon in cated empyema, and other pathogens are much 1640. Empyema necessitatis typically develops less common in these patients.11 However, the over a period of 4 to 8 weeks and is associated patient’s history of pneumococcal vaccination with pain, swelling, and lymphadenopathy of the makes this pathogen unlikely. Other aerobic anterolateral chest, often without fever; these in her tracheal secretions could cause features were seen in this case. It can also result pneumonia1; of these, only S. aureus has been in a pleurocutaneous or bronchopleurocutaneous reported in patients with empyema necessitatis. fistula, which was not seen in this case. René Both S. pneumoniae and S. aureus would be expected Laennec succinctly described its pathogenesis in to cause fever, which was not seen in this case. 1819 as follows: “When, as the result of chronic Poor oral hygiene promotes growth of bacteria , a gangrenous eschar forms on the pleura, that can cause ,12 including aerobes it sometimes happens that the effusion infiltrates such as S. pneumoniae but also anaerobes that can- through the intercostal muscles at this point, and not be detected on a routine culture of tracheal comes to form under the skin an abscess whose secretions. Chief among anaerobes that could natural or artificial opening provides, in a few cause empyema necessitatis is A. israelii. Additional rare cases, a healing of the empyema. These spe- factors that increase the likelihood of pulmonary cies of abscess, known since the origin of the actinomycosis in this case include the risk of aspi-

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ration, subacute course, and absence of fever. Dr. Samuel M. Moskowitz’s Pulmonary actinomycosis is often polymicrobi- Diagnosis al, with gram-positive bacteria or anaerobes as common coisolates,13 and its parenchymal com- Empyema necessitatis, with pneumonia of the ponent may cavitate. Small-to-medium-sized pleu- right lower lobe and empyema of the right pleural ral effusions may occur, and chest-wall invasion cavity caused by actinomyces species. may result in early rib erosion, which was seen in this child. I suspect that an actinomyces spe- Pathological Discussion cies was her primary pathogen. If a neoplasm were likely in this case, I might Dr. Eugene J. Mark: The diagnostic procedure was suggest the use of positron-emission tomogra- a of the soft-tissue mass of the chest wall. phy (PET) or magnetic resonance imaging (MRI) Histopathological examination revealed an ab- to delineate the tumor burden or ultrasound- scess with purulent inflammation (Fig. 3A), sur- guided or CT-guided percutaneous aspiration to rounded by granulomatous inflammation and obtain a tissue sample. In cases of infection or fibrosis (Fig. 3B). Staining with hematoxylin and inflammation that is confined to the pleural and eosin revealed a sulfur granule in the abscess parenchymal compartments, my preferred ap- (Fig. 3A). Filamentous structures were visible at proach would be video-assisted thoracoscopic the periphery of the sulfur granule; on silver surgery to facilitate pleural drainage and decor- staining, the filamentous structures could be tication and to obtain a lung-biopsy specimen, seen both creating the sulfur granule (Fig. 3C) as indicated. For this chest-wall lesion, I would and extending as bacillary organisms from the favor exploratory thoracotomy to obtain a biopsy periphery of the sulfur granule (Fig. 3D). These specimen and to permit open débridement or morphologic findings are typical of actinomyces resection. species. Dr. Nancy Lee Harris (Pathology): Dr. Ryan, Both actinomyces species and nocardia spe- would you tell us the thinking of the clinical cies are filamentous bacteria, with branching team and describe the diagnostic procedure? segments that often vary as positive or negative Dr. Daniel P. Ryan (Pediatric Surgery): We were on Gram’s staining. Actinomyces are found in very concerned that the multifocal nodular pleu- the sulfur granules and not in the surrounding ral lesions and the large lump on her chest wall inflammation. — which was not fluctuant or warm and did not Cultures of the tissue and abscess specimens have typical signs of infection — represented a grew A. israelii and Aggregatibacter (formerly Acti- neoplastic process. We brought her to the oper- nobacillus) actinomycetemcomitans (Fig. 3E and 3F). ating room to perform a biopsy of the mass and Aggregatibacter is a gram-negative facultative to place a thoracostomy tube to drain the pleural nonmotile rod that is frequently isolated together fluid. We made a small incision over the chest- with actinomyces. It is an oral commensal organ- wall mass. There was no subcutaneous edema, ism often found in association with localized and the mass itself was somewhat gray in ap- aggressive periodontitis.14-16 pearance. We performed an incisional biopsy, It is not clear to me in this case whether the which released yellow that contained small, pleuropulmonary infection is due to aspiration white, solid granules (≤1 mm in size). Then, we from the oral cavity or whether the trachea or inserted a drain in the mass. We located the the soft tissue around the trachea is infected pleural effusion and placed a , which with actinomyces. The closest analogy that I drained clear fluid. At that point, we decided not have found is involvement of tissue around the to perform thoracoscopy. innominate artery that results in a pseudoaneu- rysm.17 Clinical Diagnosis Dr. Harris: Dr. Pasternack, would you tell us how you treated the patient and how she is doing? Possible malignant tumor of the chest wall or Dr. Mark Pasternack (Pediatric Infectious Dis- pleura. eases): This patient had a classic presentation of

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A B

C D

E F

Figure 3. Chest-Wall–Biopsy Specimen. Hematoxylin and eosin staining shows purulent and histiocytic inflammation in adipose tissue and a sulfur granule (dark blue) amid the inflammation (Panel A); there is fibrosis in the adipose tissue that resulted from the histiocytic inflammation (Panel B). Methenamine silver staining of the tissue sample shows the filamentous forms of the or- ganism creating a relatively solid nodule (the sulfur granule) (Panel C); the filamentous forms also can be seen ex- tending from the periphery of the nodule (Panel D). Gram’s staining of smears of the cultures shows gram-positive rods, which were identified as Actinomyces israelii (Panel E), and gram-negative rods identified as Aggregatibacter actinomycetemcomitans (Panel F). (Panels E and F are courtesy of Dr. JiYeon Kim [Pathology].) thoracic actinomycosis. The findings in the soft of acute infection, and radiologic evidence of an tissue of the chest wall, indolent clinical pro- apparent thoracic mass led to the initial consid- gression, absence of fever, signs and symptoms eration of a malignant process. The diagnosis of

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infection was established only at the time of I thought the discussion had gone far enough surgical exploration. with actinomyces and elected not to delve into Dr. Rosenthal and I were consulted postop- six-syllable coinfectants. eratively, after the Gram’s stain of the chest-wall A Physician: Because of the upper-airway ab- abscess revealed pleomorphic gram-positive rods. normalities, is this patient at risk for a recur- In many cases of actinomycosis, cultures remain rence of this disease? negative, perhaps because of previous adminis- Dr. Pasternack: This is clearly a very rare com- tration of antibiotics or exposure of the speci- plication of tracheostomy, and one would have to men to air. However, in this case, the culture think, as Dr. Moskowitz has suggested, that as- grew not only A. israelii but also the fastidious oral piration led to this complication. The patient cer- gram-negative pathogen A. actinomycetemcomitans. tainly might be at risk for reaspiration. Since the child was known to have virulent Dr. Harris: In retrospect, do you think that the pathogens in preoperative respiratory secretions, episodes of bleeding that occurred 6 weeks be- including methicillin-susceptible S. aureus and fore admission, with the finding of consolidation Pseudomonas aeruginosa (in a culture that was ob- in the right lower lobe on imaging studies, rep- tained on the day of admission), we initiated resented the beginning of this process? single-agent parenteral antibiotic therapy with Dr. Pasternack: I suspect that this was the case. imipenem. A peripherally inserted central cath- I reviewed the films from the admission at MEEI, eter was placed for the administration of intra- and the possibility that this was atelectasis of the venous antibiotic therapy at home. After nearly right lower lobe was reasonable. The upper-air- 5 weeks of therapy, acute fevers developed, with way symptoms improved, so the imaging finding temperatures exceeding 40°C. The patient was in the lung was thought to not be related and readmitted to this hospital. Blood cultures were was not evaluated at follow-up. negative, and follow-up CT showed resolution of the chest-wall lesions, with residual pleural thick- Anatomical Diagnosis ening and improving consolidation in the right lower lobe. Her fever persisted despite discontinu- Infection of the chest wall (empyema necessitatis) ation of imipenem and initiation of with Actinomyces israelii and Aggregatibacter actino- therapy. She defervesced after her therapy was mycetemcomitans. transitioned to oral doxycycline and she under- This case was discussed at Pediatric Grand Rounds. went removal of the catheter. Dr. Moskowitz reports receiving fees for serving on advisory boards from Vertex Pharmaceuticals; consulting fees from The patient had a favorable response to the EnBiotix, MCIC Vermont, Kala Pharmaceuticals, Pfizer, and doxycycline therapy and received a 1-year course Cowen Group; and grant support from Gilead Sciences, Novar- of therapy. Three years later, she is currently well, tis, Rempex Pharmaceuticals, Kala Pharmaceuticals, Vertex Pharmaceuticals, and Savara Pharmaceuticals; as well as hold- and she and her family are considering recon- ing a pending patent for intermediate-metabolism products structive surgery that might permit removal of the that potentiate antibiotics in bacterial infec- tracheostomy tube. tions (U.S. application number, 61,871,554). Dr. Mark reports providing expert testimony in litigation regarding asbestos Dr. Harris: Are there questions or comments exposure. No other potential conflict of interest relevant to for any of our discussants? Dr. Moskowitz, do you this article was reported. have any comments? Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Dr. Moskowitz: I was concerned that there was We thank Drs. Bernard Kinane, Mark Pasternack, and Jessica a polymicrobial component to this infection, but Rosenthal for assistance with preparing the case history.

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