Isolated Adrenal Cryptococcosis, Diagnosed by Fine-Needle Aspiration Biopsy: A Case Report Rubina Cocker, M.D.,1* Sean A. McNair, M.P.H, C.T., (A.S.C.P.),2 Leonard Kahn, M.D.,3 Sean Kwon, M.D.,4 Xin Ding, S.C.T. (A.S.C.P.),5 Vadim Zeltsman, M.D.,6 and Chris Sung, M.D.7
This report documents a case of isolated adrenal gland cryptococcosis without the often reported component of concomitant meningitis or Addison’s disease in an immune competent patient. Furthermore, both the patient’s lung cancer and adrenal infection with cryptococcus were incidentally discovered during work-up for syncope in the setting of hyponatremia. This case also underscores the diagnostic value of fine-needle aspiration biopsy in this unusual presentation. Diagn. Cytopathol. 2014;42:899–901. VC 2014 Wiley Periodicals, Inc. Key Words:
cryptococcus; adrenal; FNA biopsy
Cryptococcal infection usually presents as disseminated disease, often with involvement of the adrenal glands.1 To the best of our knowledge, only three cases of isolated involvement of the adrenal glands diagnosed using fineneedle aspiration (FNA) biopsy have been reported. The yeast forms of these species are covered by a thin layer of glycoprotein capsular material with a 1 Division of Cytopathology, North Shore Long Island Jewish Health System Laboratories, Lake Success, New York 2 North Shore-Long Island Jewish Health System Laboratories, Division of Cytopathology, Lake Success, New York 3 North Shore-Long Island Jewish Health System Laboratories, Division of Anatomic Pathology, Lake Success, New York 4 North Shore-Long Island Jewish Health System, Division of Thoracic Surgery, Great Neck, New York 5 North Shore Long Island Jewish health System Laboratories, Division of Cytopathology, Lake Success, New York 6 North Shore- Long Island Jewish Health System, Division of Thoracic Surgery, Lake Success, New York 7 Long Island Jewish Medical Center, Department of Radiology, New Hyde Park, New York *Correspondence to: Rubina Cocker, M.D., Attending Cytopathologist, North Shore Long Island Jewish Health System Laboratories, 6 Ohio Drive Suite 202, Lake Success, New York 11042, USA. E-mail: [email protected] Received 18 February 2013; Accepted 3 December 2013 DOI: 10.1002/dc.23079 Published online 8 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
C 2014 WILEY PERIODICALS, INC. V
gelatin-like consistency, which amongst other functions, serves to help extract nutrients from soil.2,3 Cell block sections from positive FNA cases when stained with mucicarmine show a characteristic pink staining of the capsule. Radiologic imaging and FNA of the adrenal gland is often helpful in the diagnosis of adrenal gland mass lesions.4 Bilateral adrenal enlargement can be caused by metastatic disease, hyperplasia, or infection and a definitive diagnosis can be readily provided using FNA.4–7
Case Presentation A 52-year-old male presented in September 2011 with complaints of weight loss and malaise for 3 weeks. Routine laboratory blood analysis revealed a low sodium level of 120 mg. Two days later, the patient developed syncope and was admitted to an outside hospital where he was diagnosed with 2/2 adrenal insufficiency but no systemic disease was found. After the patient was clinically stabilized, he was discharged to follow-up with imaging studies. In October 2011, a CT scan showed a single nodule in the right lower lobe of lung and incidental bilateral adrenal nodules. An FNA of the right lung mass was diagnostic for an adenocarcinoma while that of the left adrenal gland was interpreted as non-diagnostic. In December 2011, a positron emission tomography (PET) scan revealed mild hypermetabolic activity in the right lung and bilateral adrenal glands. Additional MRI obtained to exclude metastatic disease and paraneoplastic syndrome confirmed the presence of bilateral adrenal nodules measuring 2.7 cm and 1.7 cm. These nodules showed the absence of signal suppression on the “out of phase” images, a finding which is inconsistent with benign adenomata. No further evidence of adrenal insufficiency was found. Peripheral blood analysis showed a WBC count of 6.2 K/uL, RBC count of 4.54 M/uL, a hemoglobin level Diagnostic Cytopathology, Vol. 42, No 10
899
Diagnostic Cytopathology DOI 10.1002/dc
COCKER ET AL.
Fig. 1. CT guided FNA biopsy shows needle placement in the right adrenal nodule using a transhepatic approach. Fig. 3. Papanicolau stain displays numerous yeasts engulfed by a macrophage. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Fig. 2. Diff-Quik stain shows yeasts in a background of crystals and necrotic debris. Giemsa stains the body and the serum around the edge of the non-staining capsule. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
of 13.4 g/Dl, and a hematocrit of 40%. A metabolic panel displayed a sodium serum level of 139 mmol/L, a potassium serum level of 3.7 mmol/L, a chloride serum level of 94 mmol/L, and a glucose level of 81 mg/dL. FNA of the right adrenal nodule (Fig. 1) was performed using CT guidance with the Phillips PercuNav image fusion and navigation system, with a 22 gauge coaxial needle via a transhepatic approach. Four passes were done and the specimen was sent for both microbiological analysis and cytological interpretation. An on-site cytologic adequacy evaluation was performed and a preliminary diagnosis of cryptococcosis was rendered on air-dried Diff-Quik stained slides (Fig. 2). Several smears were made and fixed in 70% ETOH for further confirmation by special stains. Material was also sent for microbiological analysis. The diagnosis of cryptococcosis was confirmed by identification of cryptococcal yeasts on both the Grocott-methenamine silver stain (GMS) and a mucicarmine stain. All microbiologic cultures were negative after 4 weeks incubation, highlighting the 900
Diagnostic Cytopathology, Vol. 42, No 10
utility of FNA biopsy. However, the patient was found to have a serum cryptococcal titer of 1:16 indicative of active cryptococcosis. Treatment with fluconazole at 800 mg/day was initiated for 2 weeks prior to his right lower lobectomy with mediastinal lymph node resection in February 2012. His final surgical pathology report showed a mucinous adenocarcinoma, pT1b pN0 pMx, stage IA. No evidence of cryptococcal involvement of the lung was found. Patient was discharged to continue treatment with oral fluconazole for his adrenal cryptococcosis. At six month follow-up, in August 2012, he was found to be asymptomatic with a negative cryptococcal titer. His adrenal nodules remained unchanged. The patient declined adrenalectomy and as of January 2013 was asymptomatic and returned to work.
Cytologic Findings A total of 13 slides were prepared for cytologic evaluation, including 5 air-dried Diff Quik smears, 3 fixed smears for Papanicolau staining, 3 fixed slides submitted for GMS staining, and 2 histologic sections of formalin fixed, paraffin embedded cell block material. Initial evaluation of Diff-Quik stained slides revealed faintly staining spherical organisms in a background of abundant necrotic debris. Papanicolau staining revealed abundant small ovoid yeasts with occasional tear-drop budding (Fig. 3). GMS stain was positive for yeast forms with narrowbased budding (Fig. 4). Mucicarmine stain was positive and showed strongly positive capsular material (Fig. 5).
Discussion Primary infection by cryptococcus species usually occurs in the lung. Isolated involvement by this fungus of the adrenal glands especially in an immune competent person is rare. Adrenal gland involvement also more commonly occurs with meningoencephalitis, which was not identified
Diagnostic Cytopathology DOI 10.1002/dc
ISOLATED ADRENAL CRYPTOCOCCOSIS BY FNAB
Fig. 4. Grocott’s Methenamine Silver stain (GMS) displays yeasts with occasional narrow-based budding. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
in our patient.6,7 Only four reports of isolated adrenal cryptococcosis without meningoencephalitis have been published.6–8 Powers et al. documented a case of adrenal cryptococcosis in a patient who presented with primary adrenal insufficiency, and in which an FNA established the diagnosis whereas blood and bone marrow cultures, serology, and bone marrow examination were negative.2 Liu et al. described a case of primary adrenal cryptococcosis diagnosed post-adrenalectomy. The patient presented with diabetes mellitus and roentgenographic findings were suggestive of a malignant tumor.3 Matsuda et al. described a case of adrenal cryptococcosis in a patient who also presented with adrenal insufficiency.4 FNA cytology established the diagnosis of cryptococcus. Takeshita et al. described a case which is similar to ours in that a generally healthy immune competent man presented with bilateral adrenal masses. A diagnosis of primary adrenal cryptococcosis was established by a transhepatic FNAB.9 Disseminated cryptococcosis usually occurs in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS), or with hematopoietic malignancies and can involve many organ-systems, including the skin, eyes, lymph nodes, bone, and adrenals. Studies have shown that adrenal cryptococcosis especially with adrenal insufficiency may not respond well to antifungal treatment and often requires surgical intervention including adrenalectomy.8 Our case report is unusual in that the patient has clinically improved on conservative antifungal chemotherapy for his isolated adrenal cryptococcosis at one year postdiagnosis. The association with a pulmonary adenocarcinoma is also unusual but most likely represents a fortuitous occurrence. The radiologic features in all these cases
Fig. 5. Mucicarmine stain displaying spherical organisms with a mucopolysaccharide capsular rim. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
are those of a mass lesion, often favoring adrenal malignancy. The current case illustrates the great utility of cytology in establishing a diagnosis in adrenal mass lesions. FNA is also the most cost-effective diagnostic modality in the management of adrenal gland mass lesions.
References 1. Elhence P, Bansal R. Cryptococcosis presenting as anterior neck swelling in an immunocompetent man: A case report. Acta Cytol 2010;54:1130–1132. 2. Powers CN, Rupp GM, Maygarden SJ, Frable WJ. Fine-needle aspiration cytology of adrenal cryptococcosis: A case report. Diagn Cytopathol 1991;7:88–91. 3. Liu YC, Cheng DL, Liu CY, Yen MY, Wang RS. Isolated cryptococcosis of the adrenal gland. J Intern Med 1991;230:285–287. 4. Matsuda Y, Kawate H, Okishige Y, et al. Successful management of cryptococcosis of the bilateral adrenal glands and liver by unilateral adrenalectomy with antifungal agents: A case report. BMC Infect Dis 2011;11:340. 5. Gustafson KS, Feldman L. Cryptococcal lymphadenitis diagnosed by fine-needle aspiration biopsy. Diagn Cytopathol 2007;35: 103–104. 6. Lumachi F, Basso SM, Borsato S, et al. Role and cost-effectiveness of adrenal imaging and image-guided FNA cytology in the management of incidentally discovered adrenal tumours. Anticancer Res 2005;25:4559–4562. 7. Tirabassi G, Kola B, Ferretti M, et al. Fine-needle aspiration cytology of adrenal masses: A re-assessment with histological confirmation. J Endocrinol Invest 2012;35:590–594. 8. Kawamura M, Miyazaki S, Mashiko S, et al. Disseminated cryptococcosis associated with adrenal masses and insufficiency. Am J Med Sci 1998;316:60–64. 9. Takeshita A, Nakazawa H, Akiyama H, et al. Disseminated cryptococcosis presenting with adrenal insufficiency and meningitis: Resistant to prolonged antifungal therapy but responding to bilateral adrenalectomy. Intern Med 1992;31:1401.
Diagnostic Cytopathology, Vol. 42, No 10
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This report documents a case of isolated adrenal gland cryptococcosis without the often reported component of concomitant meningitis or Addison’s disease in an immune competent patient. Furthermore, both the patient’s lung cancer and adrenal infection with cryptococcus were incidentally discovered during work-up for syncope in the setting of hyponatremia. This case also underscores the diagnostic value of fine-needle aspiration biopsy in this unusual presentation. Diagn. Cytopathol. 2014;42:899–901. VC 2014 Wiley Periodicals, Inc. Key Words:
cryptococcus; adrenal; FNA biopsy
Cryptococcal infection usually presents as disseminated disease, often with involvement of the adrenal glands.1 To the best of our knowledge, only three cases of isolated involvement of the adrenal glands diagnosed using fineneedle aspiration (FNA) biopsy have been reported. The yeast forms of these species are covered by a thin layer of glycoprotein capsular material with a 1 Division of Cytopathology, North Shore Long Island Jewish Health System Laboratories, Lake Success, New York 2 North Shore-Long Island Jewish Health System Laboratories, Division of Cytopathology, Lake Success, New York 3 North Shore-Long Island Jewish Health System Laboratories, Division of Anatomic Pathology, Lake Success, New York 4 North Shore-Long Island Jewish Health System, Division of Thoracic Surgery, Great Neck, New York 5 North Shore Long Island Jewish health System Laboratories, Division of Cytopathology, Lake Success, New York 6 North Shore- Long Island Jewish Health System, Division of Thoracic Surgery, Lake Success, New York 7 Long Island Jewish Medical Center, Department of Radiology, New Hyde Park, New York *Correspondence to: Rubina Cocker, M.D., Attending Cytopathologist, North Shore Long Island Jewish Health System Laboratories, 6 Ohio Drive Suite 202, Lake Success, New York 11042, USA. E-mail: [email protected] Received 18 February 2013; Accepted 3 December 2013 DOI: 10.1002/dc.23079 Published online 8 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
C 2014 WILEY PERIODICALS, INC. V
gelatin-like consistency, which amongst other functions, serves to help extract nutrients from soil.2,3 Cell block sections from positive FNA cases when stained with mucicarmine show a characteristic pink staining of the capsule. Radiologic imaging and FNA of the adrenal gland is often helpful in the diagnosis of adrenal gland mass lesions.4 Bilateral adrenal enlargement can be caused by metastatic disease, hyperplasia, or infection and a definitive diagnosis can be readily provided using FNA.4–7
Case Presentation A 52-year-old male presented in September 2011 with complaints of weight loss and malaise for 3 weeks. Routine laboratory blood analysis revealed a low sodium level of 120 mg. Two days later, the patient developed syncope and was admitted to an outside hospital where he was diagnosed with 2/2 adrenal insufficiency but no systemic disease was found. After the patient was clinically stabilized, he was discharged to follow-up with imaging studies. In October 2011, a CT scan showed a single nodule in the right lower lobe of lung and incidental bilateral adrenal nodules. An FNA of the right lung mass was diagnostic for an adenocarcinoma while that of the left adrenal gland was interpreted as non-diagnostic. In December 2011, a positron emission tomography (PET) scan revealed mild hypermetabolic activity in the right lung and bilateral adrenal glands. Additional MRI obtained to exclude metastatic disease and paraneoplastic syndrome confirmed the presence of bilateral adrenal nodules measuring 2.7 cm and 1.7 cm. These nodules showed the absence of signal suppression on the “out of phase” images, a finding which is inconsistent with benign adenomata. No further evidence of adrenal insufficiency was found. Peripheral blood analysis showed a WBC count of 6.2 K/uL, RBC count of 4.54 M/uL, a hemoglobin level Diagnostic Cytopathology, Vol. 42, No 10
899
Diagnostic Cytopathology DOI 10.1002/dc
COCKER ET AL.
Fig. 1. CT guided FNA biopsy shows needle placement in the right adrenal nodule using a transhepatic approach. Fig. 3. Papanicolau stain displays numerous yeasts engulfed by a macrophage. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Fig. 2. Diff-Quik stain shows yeasts in a background of crystals and necrotic debris. Giemsa stains the body and the serum around the edge of the non-staining capsule. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
of 13.4 g/Dl, and a hematocrit of 40%. A metabolic panel displayed a sodium serum level of 139 mmol/L, a potassium serum level of 3.7 mmol/L, a chloride serum level of 94 mmol/L, and a glucose level of 81 mg/dL. FNA of the right adrenal nodule (Fig. 1) was performed using CT guidance with the Phillips PercuNav image fusion and navigation system, with a 22 gauge coaxial needle via a transhepatic approach. Four passes were done and the specimen was sent for both microbiological analysis and cytological interpretation. An on-site cytologic adequacy evaluation was performed and a preliminary diagnosis of cryptococcosis was rendered on air-dried Diff-Quik stained slides (Fig. 2). Several smears were made and fixed in 70% ETOH for further confirmation by special stains. Material was also sent for microbiological analysis. The diagnosis of cryptococcosis was confirmed by identification of cryptococcal yeasts on both the Grocott-methenamine silver stain (GMS) and a mucicarmine stain. All microbiologic cultures were negative after 4 weeks incubation, highlighting the 900
Diagnostic Cytopathology, Vol. 42, No 10
utility of FNA biopsy. However, the patient was found to have a serum cryptococcal titer of 1:16 indicative of active cryptococcosis. Treatment with fluconazole at 800 mg/day was initiated for 2 weeks prior to his right lower lobectomy with mediastinal lymph node resection in February 2012. His final surgical pathology report showed a mucinous adenocarcinoma, pT1b pN0 pMx, stage IA. No evidence of cryptococcal involvement of the lung was found. Patient was discharged to continue treatment with oral fluconazole for his adrenal cryptococcosis. At six month follow-up, in August 2012, he was found to be asymptomatic with a negative cryptococcal titer. His adrenal nodules remained unchanged. The patient declined adrenalectomy and as of January 2013 was asymptomatic and returned to work.
Cytologic Findings A total of 13 slides were prepared for cytologic evaluation, including 5 air-dried Diff Quik smears, 3 fixed smears for Papanicolau staining, 3 fixed slides submitted for GMS staining, and 2 histologic sections of formalin fixed, paraffin embedded cell block material. Initial evaluation of Diff-Quik stained slides revealed faintly staining spherical organisms in a background of abundant necrotic debris. Papanicolau staining revealed abundant small ovoid yeasts with occasional tear-drop budding (Fig. 3). GMS stain was positive for yeast forms with narrowbased budding (Fig. 4). Mucicarmine stain was positive and showed strongly positive capsular material (Fig. 5).
Discussion Primary infection by cryptococcus species usually occurs in the lung. Isolated involvement by this fungus of the adrenal glands especially in an immune competent person is rare. Adrenal gland involvement also more commonly occurs with meningoencephalitis, which was not identified
Diagnostic Cytopathology DOI 10.1002/dc
ISOLATED ADRENAL CRYPTOCOCCOSIS BY FNAB
Fig. 4. Grocott’s Methenamine Silver stain (GMS) displays yeasts with occasional narrow-based budding. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
in our patient.6,7 Only four reports of isolated adrenal cryptococcosis without meningoencephalitis have been published.6–8 Powers et al. documented a case of adrenal cryptococcosis in a patient who presented with primary adrenal insufficiency, and in which an FNA established the diagnosis whereas blood and bone marrow cultures, serology, and bone marrow examination were negative.2 Liu et al. described a case of primary adrenal cryptococcosis diagnosed post-adrenalectomy. The patient presented with diabetes mellitus and roentgenographic findings were suggestive of a malignant tumor.3 Matsuda et al. described a case of adrenal cryptococcosis in a patient who also presented with adrenal insufficiency.4 FNA cytology established the diagnosis of cryptococcus. Takeshita et al. described a case which is similar to ours in that a generally healthy immune competent man presented with bilateral adrenal masses. A diagnosis of primary adrenal cryptococcosis was established by a transhepatic FNAB.9 Disseminated cryptococcosis usually occurs in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS), or with hematopoietic malignancies and can involve many organ-systems, including the skin, eyes, lymph nodes, bone, and adrenals. Studies have shown that adrenal cryptococcosis especially with adrenal insufficiency may not respond well to antifungal treatment and often requires surgical intervention including adrenalectomy.8 Our case report is unusual in that the patient has clinically improved on conservative antifungal chemotherapy for his isolated adrenal cryptococcosis at one year postdiagnosis. The association with a pulmonary adenocarcinoma is also unusual but most likely represents a fortuitous occurrence. The radiologic features in all these cases
Fig. 5. Mucicarmine stain displaying spherical organisms with a mucopolysaccharide capsular rim. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
are those of a mass lesion, often favoring adrenal malignancy. The current case illustrates the great utility of cytology in establishing a diagnosis in adrenal mass lesions. FNA is also the most cost-effective diagnostic modality in the management of adrenal gland mass lesions.
References 1. Elhence P, Bansal R. Cryptococcosis presenting as anterior neck swelling in an immunocompetent man: A case report. Acta Cytol 2010;54:1130–1132. 2. Powers CN, Rupp GM, Maygarden SJ, Frable WJ. Fine-needle aspiration cytology of adrenal cryptococcosis: A case report. Diagn Cytopathol 1991;7:88–91. 3. Liu YC, Cheng DL, Liu CY, Yen MY, Wang RS. Isolated cryptococcosis of the adrenal gland. J Intern Med 1991;230:285–287. 4. Matsuda Y, Kawate H, Okishige Y, et al. Successful management of cryptococcosis of the bilateral adrenal glands and liver by unilateral adrenalectomy with antifungal agents: A case report. BMC Infect Dis 2011;11:340. 5. Gustafson KS, Feldman L. Cryptococcal lymphadenitis diagnosed by fine-needle aspiration biopsy. Diagn Cytopathol 2007;35: 103–104. 6. Lumachi F, Basso SM, Borsato S, et al. Role and cost-effectiveness of adrenal imaging and image-guided FNA cytology in the management of incidentally discovered adrenal tumours. Anticancer Res 2005;25:4559–4562. 7. Tirabassi G, Kola B, Ferretti M, et al. Fine-needle aspiration cytology of adrenal masses: A re-assessment with histological confirmation. J Endocrinol Invest 2012;35:590–594. 8. Kawamura M, Miyazaki S, Mashiko S, et al. Disseminated cryptococcosis associated with adrenal masses and insufficiency. Am J Med Sci 1998;316:60–64. 9. Takeshita A, Nakazawa H, Akiyama H, et al. Disseminated cryptococcosis presenting with adrenal insufficiency and meningitis: Resistant to prolonged antifungal therapy but responding to bilateral adrenalectomy. Intern Med 1992;31:1401.
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