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Histoplasmosis presenting with multiple pulmonary nodules. A case mimicking radiological features of pulmonary metastasis

Histoplasmose apresentando múltiplos nódulos pulmonares. Um caso simulando características radiológicas de metástase pulmonar

Abstracts

We present a case of histoplasmosis with multiple pulmonary nodules in a patient with a history of melanoma. This case closely simulated malignancy, including the presence of feeding vessel sign, which occurs in pulmonary metastasis. We emphasize the need to be aware of this infection in areas where histoplasmosis is endemic.

Histoplasmosis; Histoplasma capsulatum ; Pulmonary nodules; Metastatic lesions


Apresentamos caso de histoplasmose com múltiplos nódulos pulmonares em paciente com história de melanoma. Este caso simula malignidade, incluindo o sinal de vaso nutridor que ocorre na metástase pulmonar. Enfatizamos a necessidade de considerar esta infecção em áreas onde a histoplasmose é endêmica.


INTRODUCTION

Classic histoplasmosis, a granulomatous disease caused by the dimorphic fungus Histoplasma capsulatum var. capsulatum (H. capsulatum), is endemic in certain areas of North and Latin America99. Mata-Essayag S, Colella MT, Roselló A, de Capriles CH, Landaeta ME, de Salazar CP, et al. Histoplasmosis: a study of 158 cases in Venezuela, 2000-2005. Medicine (Baltimore). 2008;87:193-202.. Brazil is an area of higher prevalence of cases1313. Severo LC, Oliveira FM, Irion K, Porto NS, Londero AT. Histoplasmosis in Rio Grande do Sul, Brazil: a 21-years experience. Rev Inst Med Trop Sao Paulo. 2001;43:183-7..

The vast majority of infections with H. capsulatum are completely asymptomatic or, at least, subclinical. The disease is resolved spontaneously over a period of 2-4 weeks. The roentgenographic signs are resolved completely in 2-4 months or leave calcifield hilar and/or mediastinal lymph nodes or pulmonary histoplasmomas66. Goodwin RA, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine (Baltimore). 1981;60:231-66.,1414. Severo LC, Lemos ACM, Lacerda HR. Mediastinal histoplasmosis: report of the first two Brazilian cases of mediastinal granuloma. Rev Inst Med Trop Sao Paulo. 2005;47:103-5.

15. Unis G, Pêgas KP, Severo LC. Histoplasmoma pulmonar no Rio Grande do Sul. Rev Soc Bras Med Trop. 2005;38:11-4.
-1616. Wheat LJ, Conces D, Allen SD, Blue-Hnidy D, Loyd J. Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management. Semin Respir Crit Care Med. 2004;25:129-44..

On the other hand, histoplasmosis may mimic metastatic lesions by having similar radiographic findings when presenting the tendency to be peripheral on the lower lobes. The aim of this report is to present one of such case with feeding vessel sign that occurs in pulmonary metastasis1010. Murata K, Takahashi M, Mori M, Kawaguchi N, Furukawa A, Ohnaka Y, et al. Pulmonary metastatic nodules: CT-pathologic correlation. Radiology. 1992;182:331-5. in a patient with a history of previously diagnosed melanoma.

CASE REPORT

We present a 64-year-old asymptomatic woman with a history of a wide local excision of a superficial melanoma (Clark level II 55. Gimotty PA, Botbyl J, Soong SJ, Guerry D. A population-based validation of the American Joint Committee on Cancer Melanoma Staging System. J Clin Oncol. 2005;31:8065-75.) eight years ago. During this time she showed no signs of recurrence upon periodic examinations. Presently, a chest x-ray revealed multiple pulmonary nodules in the right lower lobe. On physical examination, she appeared well. No lymphadenopathy was found. A high-resolution axial computed tomography (CT) scan with maximum intensively projection (MIP) technique that highlighted pulmonary nodules showed numerous small nodules in random distribution. The high-resolution coronal CT scan with MIP technique demonstrated a right lung nodule with feeding vessel sign, which occurs in pulmonary metastasis (Fig. 1 and 2). Histopathological examinations of lung biopsy specimens stained by hematoxylin and eosin (H&E) showed multiple small white nodules (0.5 - 1.0 cm), and tuberculoid granuloma with central caseous necrosis surrounded by fibrous connective tissue presenting giant cells (Fig. 3A and B). Replicate section stained by Gomori-Grocott methenamine silver (GMS) showed multiple small, round to oval yeasts of H. capsulatum. The patient was treated with itraconazole, 200 mg/day for one month, followed by 100 mg daily for six weeks. The antifungal treatment was suspended after six weeks according to the guideline 20071717. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807-25.. In a recent follow-up she appeared to be in good clinical condition.

Fig. 1
High-resolution axial CT scan with MIP technique that highlighted pulmonary nodules shows numerous small nodules in random distribution.

Fig. 2
High-resolution coronal CT scan with MIP technique demonstrated a right lung nodule with feeding vessel sign that occurs in pulmonary metastasis (arrow).

Fig. 3
Tuberculous granuloma. a) An area central of caseous necrosis is surrounded by fibroblastic proliferation, macrophages, and b) multinucleated giant cell (H&E, x40 and x400, respectively). Within the amorphous necrotic debris, c) the ovoid rarely, budding yeast forms of H. capsulatum are distinguishable (GMS, x1000).

Finally, in a retrospective mycological evaluation the serologic (immunodiffusion) test for histoplasmosis was negative, and the epidemiologic history showed that the patient had cleaned out a bat-infested attic three years earlier.

DISCUSSION

Microconidia of H. capsulatum (2 to 5 µm) are small enough to be inhaled into the lungs during environmental disturbances. These primary infectious particles are observed in the mycelial form of the fungus, which finds a natural habitat in soil with high nitrogen content, such as areas contaminated with bat and chicken excrements. Prevention of histoplasmosis infections can often be accomplished by avoiding such areas. If this is not possible, any procedure that minimizes the production of aerosolized dust should be instituted. Especially given that after a heavy exposure, most infections are symptomatic and result in acute pulmonary histoplasmosis22. Deepe GS Jr. Histoplasma capsulatum. In: Mandell GL, Bennett JE, Dolin, editors. R Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 3305-18.,1212. Severo LC, Petrillo VF, Camargo JJ, Geyer GR, Porto NS. Acute pulmonary histoplasmosis and first isolation of Histoplasma capsulatum from soil of Rio Grande do Sul, Brazil. Rev Inst Med Trop Sao Paulo. 1986;28:51-5..

In this case, the patient was exposed to inoculum for a short period of time and developed mild clinical symptoms, and later, chest roentgenograns revealed some peripheral lung nodules, mimicking metastatic lesions. MACKIE et al. report a similar case, in which a patient with known metastatic melanoma who was presenting for restaging was initially considered to have widespread mediastinal and cervical metastasis on the bases of the imaging findings88. Mackie GC, Pohlen JM. Medistinal histoplasmosis: F-18 FDG PET and CT findings simulating malignant disease. Clin Nucl Med. 2005;30:633-5..

The incidence of melanoma has increased during the past several decades, and approximately 70% of new cases of melanoma are thin lesions11. Bonfá R, Bonamigo RR, Bonfá R, Duro KM, Furian RD, Zelmanowicz AM. A precocidade diagnóstica do melanoma cutâneo: uma observação no sul do Brasil. An Bras Dermatol. 2011;86:215-21.,77. Jemal A, Devesa SS, Hartge P, Tucker MA. Recent trends in cutaneous melanoma incidence among whites in the United States. J Natl Cancer Inst. 2001;93:678-83.. Patients with these lesions are generally considered to be at low risk for metastasis44. Faries MB, Wanek LA, Elashoff D, Wright BE, Morton DL. Predictors of occult nodal metastasis in patients with thin melanoma. Arch Surg. 2010;145:137-42.. However, it is well known that a portion of this group will eventually experience disease recurrence44. Faries MB, Wanek LA, Elashoff D, Wright BE, Morton DL. Predictors of occult nodal metastasis in patients with thin melanoma. Arch Surg. 2010;145:137-42., which was suspected to occur in our case with a melanoma Clark level II history.

In conclusion, histoplasmosis as a self-limited disease in most patients continues to complicate the evaluation of pulmonary nodules and often leads to surgical resection. Exploration in patients with presumed pulmonary metastases from melanoma is justified to rule out benign disease1111. Pogrebniak HW, Stovroff M, Roth JA, Pass HI. Resection of pulmonary metastases from malignant melanoma: results of a 16-year experience. Ann Thorac Surg. 1988;46:20-3.. Ideally, samples of the lung lesions should be taken for culture. This procedure is not always possible, as in this case, because the tissue was immersed in formalin. Therefore, the pathologist, rather than microbiologist, must assume the responsibility for the identification of the infection agent by special tissue stain33. El-Zammar OA, Katzenstein A-L. Pathologic diagnosis of granulomatous lung disease: a review. Histopathology. 2007;50:289-310..

REFERENCES

  • 1
    Bonfá R, Bonamigo RR, Bonfá R, Duro KM, Furian RD, Zelmanowicz AM. A precocidade diagnóstica do melanoma cutâneo: uma observação no sul do Brasil. An Bras Dermatol. 2011;86:215-21.
  • 2
    Deepe GS Jr. Histoplasma capsulatum. In: Mandell GL, Bennett JE, Dolin, editors. R Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 3305-18.
  • 3
    El-Zammar OA, Katzenstein A-L. Pathologic diagnosis of granulomatous lung disease: a review. Histopathology. 2007;50:289-310.
  • 4
    Faries MB, Wanek LA, Elashoff D, Wright BE, Morton DL. Predictors of occult nodal metastasis in patients with thin melanoma. Arch Surg. 2010;145:137-42.
  • 5
    Gimotty PA, Botbyl J, Soong SJ, Guerry D. A population-based validation of the American Joint Committee on Cancer Melanoma Staging System. J Clin Oncol. 2005;31:8065-75.
  • 6
    Goodwin RA, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine (Baltimore). 1981;60:231-66.
  • 7
    Jemal A, Devesa SS, Hartge P, Tucker MA. Recent trends in cutaneous melanoma incidence among whites in the United States. J Natl Cancer Inst. 2001;93:678-83.
  • 8
    Mackie GC, Pohlen JM. Medistinal histoplasmosis: F-18 FDG PET and CT findings simulating malignant disease. Clin Nucl Med. 2005;30:633-5.
  • 9
    Mata-Essayag S, Colella MT, Roselló A, de Capriles CH, Landaeta ME, de Salazar CP, et al. Histoplasmosis: a study of 158 cases in Venezuela, 2000-2005. Medicine (Baltimore). 2008;87:193-202.
  • 10
    Murata K, Takahashi M, Mori M, Kawaguchi N, Furukawa A, Ohnaka Y, et al. Pulmonary metastatic nodules: CT-pathologic correlation. Radiology. 1992;182:331-5.
  • 11
    Pogrebniak HW, Stovroff M, Roth JA, Pass HI. Resection of pulmonary metastases from malignant melanoma: results of a 16-year experience. Ann Thorac Surg. 1988;46:20-3.
  • 12
    Severo LC, Petrillo VF, Camargo JJ, Geyer GR, Porto NS. Acute pulmonary histoplasmosis and first isolation of Histoplasma capsulatum from soil of Rio Grande do Sul, Brazil. Rev Inst Med Trop Sao Paulo. 1986;28:51-5.
  • 13
    Severo LC, Oliveira FM, Irion K, Porto NS, Londero AT. Histoplasmosis in Rio Grande do Sul, Brazil: a 21-years experience. Rev Inst Med Trop Sao Paulo. 2001;43:183-7.
  • 14
    Severo LC, Lemos ACM, Lacerda HR. Mediastinal histoplasmosis: report of the first two Brazilian cases of mediastinal granuloma. Rev Inst Med Trop Sao Paulo. 2005;47:103-5.
  • 15
    Unis G, Pêgas KP, Severo LC. Histoplasmoma pulmonar no Rio Grande do Sul. Rev Soc Bras Med Trop. 2005;38:11-4.
  • 16
    Wheat LJ, Conces D, Allen SD, Blue-Hnidy D, Loyd J. Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management. Semin Respir Crit Care Med. 2004;25:129-44.
  • 17
    Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807-25.

Publication Dates

  • Publication in this collection
    May-Jun 2013

History

  • Received
    12 Sept 2012
  • Accepted
    9 Nov 2012
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