Suppurative Inflammation With Microabscess and Pseudocyst ...dermpathmd.com/skin_tags/Suppurative Inflammation... · microabscess formation. When present, the granulomatous inflammation

Anatomic Pathology / RAPID-GROWING MYCOBACTERIUM SPECIES

Suppurative Inflammation With Microabscess andPseudocyst Formation Is a Characteristic HistologicManifestation of Cutaneous Infections With Rapid-Growing Mvcobacterium Species

Ashley D_ Gable, MD, Derek K. Marsee, MD, PhD, Dan A. Milner, MD, and Scott R. Granter, MD

DOl: 10.1309/DPCLAwWONTB74JNB

Key Words: Rapid-growing Mycobacterium; Mycobacterium abscess us; Mycobacterium chelonae; Suppuration; Abscess

Upon completion of this activity you will be able to:• describe the classical findings of cutaneous involvement by classical

Mycobacterium tuberculosis.• list histologic features in skin biopsies that should raise suspicion of

rapidly growing atypical mycobacterial infections.• list the special stains that are indicated in the workup of inflammatory

conditions of the skin to assist in defining possible mycobacterialinfections.

AbstractMycobacterial irifections of the skin classically

cause a granulomatous tissue reaction. We haveobserved a suppurative pattern of inflammationassociated with infections by rapid-growingMycobacterium species in immunocompromisedpatients. We report 6 cases in skin and soft tissue withan unusual but consistent lack of a predominance ofgranulomatous inflammation. Of the 6 cases, 4 hadpredominantly (~75%)suppurative inflammation, 1case predominantly demonstrated (~75%)a mix ofacute and chronic inflammation, and 1 case showedan approximately equal contribution of suppurativeand granulomatous inflammation. All 6 cases showedabscess formation and numerous acid-fast bacilli(AFB) on AFB stain and were confirmed by tissueculture. Of these 6 cases, 2 had microabscesses withcentral pseudocysts harboring microorganisms.Five patients were taking oral prednisone, and 1had an uncharacterized immunodeficiency Thesecases highlight the need for awareness of thisunusual manifestation of infection with rapid-growing Mycobacterium species, particularly inimmunocompromised patients.

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The ASCP is accredited by the Accreditation Council for ContinuingMedical Education to provide continuing medical education for physicians.The ASCPdesignates this educational activity for a maximum of 1 AMA PRACategory 1 Credit 1M per article.

The authors of this article and the planning committee members and staffhave no relevant financial relationships with commercial interests to disclose .

Questions appear on p 642. Exam is located at www.ascp.org/ajcpcme.

Mycobacterial infections in the skin, as in other partsof the body, classically cause a granulomatous tissue reac-tion. Pathologists readily order acid-fast bacilli (AFB) stains,such as Kinyoun or Fite stain, along with fungal stains in thecontext of granulomatous inflammation. However, infectionwith AFB is often not considered in the differential diagnosisof prominent acute inflammation and abscess formation inskin and soft tissue. As a consequence, only Gram and fungalstains are often ordered in these cases. Herein, we describesuppurative response to infection with rapid-growing speciesof mycobacteria in immunocompromised patients.

Materials and Methods

We studied 6 cases of infection with rapid-growingMycobacterium species in skin and soft tissue, 5 withMycobacterium abscessus and 1 with Mycobacterium che-lonae. Of the 6 patients, 5 were taking oral prednisonefor various chronic illnesses and 1 had an uncharacterizedimmunodeficiency with a CD4 cell count of 25/IlL in theface of multiple negative HIV serologic test results. Thispatient also had chronic hepatitis B and hepatitis C virusinfections lTable 11. Of the 6 patients, 4 had multiple nod-ules on the bilateral lower extremities only, 1 had multiplepapules and nodules on all 4 extremities and 1 abscess onthe lower extremity, and 1 had a single abscess and sinustract on the chest wall. Clinical suspicion for cutaneousmycobacterial infection was present in only 2 of the 6 cases.Additional details about the clinical manifestations for eachpatient are given in lTable 21.

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Anatomic Pathology / ORIGINAL ARTICLE

ITable 11Demographic and Clinical Data for Patients With Infection by Rapid-Growing Mycobacterium Species

Case No.!Sex/Age (y) Immunosuppression Underlying Disease

l/FnO2/M/453/M/514/M/775/M/546/M/45

Oral prednisoneOral prednisoneOral prednisoneOral prednisoneOral prednisoneImmunodeficiency of unknown

etiology (HIV-; CD4 count, 25/IJU

IPFPANBilateral lung transplantation for CFcu.Sarcoidosis of liverHBV and HCV infection; uncharacterized immunodeficiency

CF, cystic fibrosis; CLL, chronic lymphocytic leukemia; HBV, hepatitis B virus; HCV, hepatitis C virus; IPF, idiopathic pulmonary fibrosis; PAN, polyarteritis nodosa.

lTable 21Data on Manifestations of Infection With Rapid-Growing Mycobacterium Species

Initial Clinical ManifestationCase No. of Cutaneous Lesions Systemic Involvement

Duration of Cutaneous Size of CutaneousLesions (mo) Lesions (em)

1234

Multiple nodules, bilateral lE onlyMultiple nodules, bilateral lE onlyAbscess and sinus tract, chest wallMultiple nodules, bilateral lE only

NoneNoneNone"Suspicious" lung opacities; patient died before

lung biopsy performed; no autopsy doneNoneNone

1-2 Not known1 1-24 Not known1 Not known

6+ Not known4 2-4parts

reac-rains,in the

56

Multiple nodules, bilateral lE onlyMultiple nodules, all 4 extremities

and single abscess on 1 lE

LE, lower extremity or extremities.

The mycobacteria were cultured using liquid and solidmedia for growth. The specimens were inoculated into a bacT/alert bottle (biolvlerieux, Durham, NC), which has a liquidmedium containing Middlebrook 7H 9 broth, oleic acid, anda mixture of antibiotic and antifungal agents (polymyxin B,amphotericin B, nalidixic acid, trimethoprim, and azlocillin).Once growth was detected by an automated system, a smearwith Kinyoun stain was made to confirm that the culturegrew AFB. Once confirmation of AFB was made, speciesidentification was attempted with genetic probes (Gen-Probetechnology [Gen-Probe, San Diego, CA] with probes forMycobacterium tuberculosis complex, Mycobacterium avium,Mycobacterium intracellulare, Mycobacterium gordonae, andMycobacterium kansasii). In our cases, the AFB were notidentified with any of our probes, so the samples were submit-ted to the Massachusetts State Laboratory. At that facility, themycobacteria species were identified by using growth charac-teristics and standard biochemical techniques.

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Results

Ofthe 6 cases, 4 (67%) histologically showed greater than75% suppurative inflammation and less than 25% granuloma-tous inflammation; 1 case (17%) showed a greater than 75%mixture of acute and chronic inflammation with less than 25%

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granulomatous inflammation; and 1 case (17%) showed 50%suppurative inflammation and 50% granulomatous inflam-mation. All 6 cases (100%) showed frank dermal abscess ormicroabscess formation. When present, the granulomatousinflammation was nonnecrotizing and was intimately admixedwith the suppurative inflammation. In 3 cases (50%), theinflammatory response was centered in the panniculus, and in2 cases (33%), the response was centered in mid and deep lev-els ofthe dermis with less prominent involvement of the super-ficial subcutis. In 1 case (17%), the inflammatory response waspresent only in the superficial and mid dermis. Ofthe 6 cases, 2(33%) cases, both with greater than 75% suppuration, showedformation of small pseudocysts within the abscesses. Thesepseudocysts were clear or filled with amorphous "fluffy" blue-gray material that on AFB staining represented AFB IImage 11and IImage 21. In all 6 cases, AFB staining revealed numerousmicroorganisms, sometimes in areas of the biopsy with mini-mal to no inflammation IImage 31 and IImage 41. Of note, 1 ofthe 6 cases was initially misdiagnosed by a surgical pathologistas necrotizing fasciitis.

DiscussionMycobacterial infections classically cause a granuloma-

tous tissue reaction in most body sites, including the skin.Therefore, AFB stains are routinely performed along with

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Gable et al R.;piDGRO\J;'L'1G MYCOBACTERIUM SPECIES

'Image 11 Pseudocyst within a dermal abscess (H&E, x400).

'Image 3' Corresponding area for Image 4 of area withminimal inflammation away from the dermal abscess (H&E,x200).

fungal stains in the context of granulomatous inflamma-tion. However, other histologic patterns have been reportedin association with cutaneous mycobacterial infections,including classical "tuberculoid" caseating granulomas, 1,2

well-formed noncaseating ("sarcoidal") granulomas.l-? sup-purative granulomas.l' dermal abscess formation.!" diffusehistiocytic infiltration,' panniculitis, 1 lichenoid dermatitismixed with granulomata.l and nonspecific chronic inflam-mati on. 1 Despite these reports, infection with AFB is oftennot considered in the differential diagnosis in skin and softtissue biopsy specimens with prominent acute inflammationand abscess formation.

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IImage 2' The pseudocyst is filled with acid-fast organisms(acid-fast bacilli stain, x400).

'Image 4' Acid-fast bacilli (AFB) are readily seen away fromthe inflammation (AFB stain, x400).

The rapid-growing Mycobacterium species, includingM abscessus, M chelonae, and Mycobacterium fortuitum, areseparated from other nontuberculous mycobacteria becauseof their tendency to grow out in culture in 3 to 5 days ratherthan the more typical 2 to 4 weeks of other Mycobacteriumspecies. These organisms are ubiquitous and rarely causesignificant clinical infection in immunocompetent hosts.However, in the past 2 decades with the emergence of AIDSand the increased use of immunosuppression in transplantrecipients and other chronically ill patients, the recogni-tion of infections caused by rapid-growing mycobacteriahas increased.f These infections often are disseminated in

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nnocompromised hosts but can also be localized to theand soft tissue. Immunocompromised patients in whomberculous mycobacterial infections develop have beened to have an increased number of cutaneous lesionsared with immunocompetent patients with similar infec-.1 The immunocompromised patients tend to have more. ent ulceration of and abscess formation within theeous lesionsJ,8 Histologically, irnmunocompromisedshow more involvement of the subcutaneous tissue with

re prominent microabscess formation."?We report a characteristic histologic reaction pattern ineous rapid-growing Mycobacterium infections in a series

i: immunocompromised patients. A high index of suspicionAFB should be present when faced with a skin or soft

::5sue sample with predominantly suppurative inflammation,especially in immunocompromised patients. In some cases,

all pseudocysts within the abscesses were found to be filledith acid-fast bacteria. We recommend routine use of an AFB

stain, in addition to Gram and fungal stains, for the histologicaluation of suppurative inflammations of skin and soft tis-

sue infections.

From the Department of Pathology, Brigham and Women'sHospital, Harvard Medical School, Boston, MA.

Address reprint requests to Dr Granter: Dept of Pathology,Brigham and Women's Hospital, 75 Francis St, Boston, MA02115.

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Anatomic Pathology / ORIGINAL ARTICLE

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3. Escalonilla P, Esteban J, Soriano ML, et aL Cutaneousmanifestations of infection by nontuberculous mycobacteria.Clin Exp Dennato!' 1998;23:214-221.

4. High WA, Evans CC, Hoang MP. Cutaneous miliarytuberculosis in two patients with HIY infection. ] Am AcadDermatol. 2004;50(5 suppl):SllO-S113.

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6. Wolinsky E. Mycobacterial diseases other than tuberculosis.Clin Infect Dis. 1992;15:1-10.

7. Bartralot R, Garcia-Patos Y, Rodriguez-Cano L, et al. Clinicalpatrerns of cutaneous nontuberculous mycobacterial infections.Br] Dennatol. 2005;152:727-734.

8. Bartralot R, Pujol RM, Garcia-Pates Y, et aL Cutaneousinfections due to nontuberculous mycobacteria: histopathologicalreview of 28 cases: comparative study between lesions observedin immunosuppressed patients and normal hosts. ] CutanPathol. 2000;27:124-129.

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