- Email: [email protected]
Adrenocortical adenoma with unusual myxoid histological pattern: a case report
188
Pathology (2009), 41(2), February
CORRESPONDENCE
whereas the patients with symptomatic infection represent only ‘the tip of the iceberg’.12 Obviously, there is a need to culture for C. difficile in order to increase sensitivity of laboratory diagnosis of CDAD and obtain isolates for further studies. However, as culture and identification take longer than 48 h, results may not be useful for making management decision, especially in case of rapidly progressive C. difficile infections. Also, culturing every faecal specimen will add significantly to the laboratory workload. One possible solution is to employ a two-step testing algorithm:13 all stool specimens are first screened using an immunoassay for glutamate dehydrogenase (GDH), an enzyme produced by all (toxigenic and non-toxigenic) strains of C. difficile. This assay has been shown to be very sensitive and a good screening test.13,14 Specimens negative for GDH are immediately reported as negative, and GDH-positive specimens are tested for the presence of toxin A and B and cultured for C. difficile. Isolates from GDH positive specimens that initially tested toxin-negative are tested again for toxin A and B, to confirm the presence of toxigenic strains. Fenner et al.14 used this algorithm and showed that a negative GDH screen allowed reliable exclusion of C. difficile, and only a small percentage of specimens (those GDH-positive and toxin-negative) needed to be cultured and isolates tested for toxin production. This approach provides the desired increase in sensitivity and specificity of laboratory diagnosis of CDAD and is cost-effective, as GDH test is less expensive than toxin tests and avoids routine culture for C. difficile great majority of stool specimens. Isolation and identification of C. difficile was once a routine procedure in clinical microbiology laboratories, but has been mostly replaced by rapid toxin tests. Consequently, clinical decisions and infection control measures are based on the results of tests less sensitive and specific than culture.1 Furthermore, without isolates which can be typed and analysed, correlation of epidemiological and clinical findings with the particular strains is impossible. It is now up to microbiologists to be innovative and implement diagnostic strategies for CDAD that will be rapid, reliable, and cost-effective and will also ensure isolates of C. difficile are available for early identification and analysis of hypervirulent strains. Every novice in the microbiology laboratory soon learns that ‘Microbiologists do it with culture . . .’. In the case of CDAD, so we should. A. Sasha Jaksic* Graeme R. Nimmo* Brian W. Dwyer{ *Division of Microbiology, Pathology Queensland—Central Laboratory, Queensland, {Infection Management Service, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia Contact Dr A. S. Jaksic. E-mail: [email protected]
1. Elliott B, Chang BJ, Golledge CL, Riley TV. Clostridium difficileassociated diarrhoea. Intern Med J 2007; 37: 561–8. 2. Kuijper EJ, Coignard B, Tull P, ESCMID Study Group for Clostridium difficile; EU Member States; European Centre for Diseases Prevention and Control. Emergence of Clostridium difficileassociated disease in North America and Europe. Clin Microbiol Infect 2006; (Suppl 6): 2–18.
3. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353: 2433–41. 4. Loo VG, Poirier L, Miller MA, et al. Predominantly clonal multiinstitutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353: 2442–9. 5. Gerding DN. New definitions will help, but cultures are critical for resolving unanswered questions about Clostridium difficile. Infect Control Hosp Epidemiol 2007; 28: 113–15, 2007. 6. Delmee M, Van Broeck J, Simon A, Janssens M, Avesani V. Laboratory diagnosis of Clostridium difficile-associated diarrhoea; a plea for culture. J Med Microbiol 2005; 54: 187–91. 7. Peterson LR, Manson RU, Paule SM, et al. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis 2007; 45: 1152–60. 8. Bartlett JG, Gerding DN. Clinical recognition and diagnosis of Clostridium difficile infection. Clin Infect Dis 2008; 46: S12–18. 9. Johal SS, Hammond J, Solomin K, James PD, Mahida YR. Clostrodium difficile associated diarrhoea in hospitalised patients: onset in the community and role of flexible sigmoidoscopy. Gut 2004; 53: 673–7. 10. Kim KH, Fekety R, Batts DH, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibioticassociated colitis. J Infect Dis 1981; 143: 42–50. 11. Riggs MM, Sethi AJ, Zabarsky TF, Eckstein EC, Jump RLP, Donskey CJ. Asymptomatic carriers are a potential source of transmission of epidemic and nonepidemic Clostridium difficile strains among LongTerm Care Facility residents. Clin Infect Dis 2007; 45: 992–8. 12. Muto CA. Asymptomatic Clostridium difficile colonisation: Is this the tip of another iceberg? Clin Infect Dis 2007; 45: 999–1000. 13. Ticehurst JR, Aird DZ, Dam LM, Borek AP, Hargrove JT, Carroll KC. Effective detection of toxigenic Clostridium difficile by a two-step algorithm including tests for antigen and cytotoxin. J Clin Microbiol 2006; 44: 1145–9. 14. Fenner L, Widmer AF, Goy G, Rudin S, Frei R. Rapid and reliable diagnostic algorithm for detection of Clostridium difficile. J Clin Microbiol 2008; 46: 328–30.
DOI: 10.1080/00313020802579235
Adrenocortical adenoma with unusual myxoid histological pattern: a case report Sir, Myxoid changes in adrenocortical neoplasms are extremely rare. They were originally described in carcinomas,1,2 and account for just 4.7% of 300 adrenocortical neoplasms in the only published series.3 Only nine adenomas with myxoid change have been reported.3–6 In this study, we describe an additional case of myxoid adrenocortical adenoma and include a review of the literature. A 44-year-old man was admitted to our hospital for the evaluation of an asymptomatic right adrenal mass detected incidentally 3 months previously. A physical examination of the abdomen was unremarkable, and laboratory findings were entirely normal except for microscopic haematuria. The patient underwent an endocrine evaluation, which included measurements of vanillylmandelic acid, homovanillic acid, epinephrine, norepinephrine, metanephrine, cortisol, 17ketosteroid, and 17-hydroxycorticoid levels, which showed no functional abnormalities. Tumour markers (carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, prostate-specific antigen) were within normal ranges. Turbo spin echo-T1 inversion recovery MRI demonstrated an oval-shaped, strongly hyperintense lesion in the right adrenal gland (Fig. 1). Laparoscopic adrenalectomy was performed, and on gross examination, the adrenal gland with attached fibroadipose tissue weighed
CORRESPONDENCE
12 g. On sectioning, the tumour was found to be 2.7 6 2.7 cm in size and was a well-circumscribed, yellowgreyish mass, with gelatinous areas admixed with whitish fibrous areas (Fig. 2). A rim of compressed adrenal tissue was also present in the mass periphery. Microscopically, the tumour was demarcated by an incomplete fibrous capsule at its periphery, in which partially atrophic adrenal gland parenchyma was found. More than 90% of the tumour mass was characterised by a myxoid background containing anastomosing cords, small nests, and pseudoglands of tumour cells that were floating loosely in an acellular myxoid background (Fig. 3A). Most of the tumour cells had regular nuclei with fine chromatin and sometimes visible nucleoli, and moderate amounts of eosinophilic cytoplasm. In limited areas, cell clusters with an amphophilic or clear vesicular cytoplasm resembling classical adrenocortical adenoma were observed. There were neither mitotic figures nor necrosis, and no evidence of vascular or capsular invasion. Diffuse histochemical staining for Alcian blue (pH
FIG. 1 Turbo spin echo-T1 inversion recovery MRI showing an ovalshaped, strong hyperintense lesion, measuring 2.5 cm in diameter, in the right adrenal gland (arrow).
FIG. 2 Cut surface of the resected adrenal mass showing a wellcircumscribed, glistening, yellowish mass. A centrally situated, whitish, scar-like area is also noted.
189
2.5) highlighted the abundance of myxoid material (Fig. 3B), which was negative for periodic acid-Schiff (PAS) and mucicarmine. Tumour cells showed immunohistochemical reactivity to vimentin and cytokeratin CAM5.2. Synaptophysin was focal, weakly positive. Cytokeratin AE1/AE3, chromogranin A, and epithelial membrane antigen (EMA) were negative. Two months after the operation, the patient remained in good condition with no signs or symptoms of tumour recurrence. Neoplasms arising from a mesodermal origin, such as liposarcoma, malignant fibrous histiocytoma, and malignant mesothelioma, can produce acidic mucopolysaccharides and show myxoid change. Although adrenal cortical tumours may be able to produce acidic mucopolysaccharides due to their mesodermal origin, myxoid tumours of the adrenal cortex are extremely rare. To the best of our knowledge, only nine cases of myxoid adrenocortical adenoma have been reported in the literature to date (Table 1).3–6 The pathogenesis of this tumour is not known. From the rare reported cases, Carney complex may be a possible underlying hereditary disease, since it is known to affect the adrenal gland and, above all, to be associated with myxoid tumours elsewhere in the body.7 A characteristic feature of these tumours is ample extracellular myxoid material, and the extent of these areas in reported cases ranges from 10% to more than 90%. The origin of myxoid material in these tumours is unknown, though it has been suggested that it might represent a degenerative process or be a product of tumour cells.8 However, this material has never been found in the cytoplasm of tumour cells, and thus, it is presumed to reflect a degenerative process rather than being a product of these cells. The architectural pattern of these tumours is variable, and includes irregular clusters, nests, anastomosing cords, and pseudoglands. The tumour cells themselves have moderate amounts of eosinophilic or slightly basophilic cytoplasm with only occasional clear cells. Occasionally it can be difficult to distinguish adrenal cortical adenoma and carcinoma, and furthermore, myxoid changes may be observed in both benign and malignant adrenocortical neoplasms. As myxoid adrenal cortical tumours are extremely rare, the usual histopathological features used to discriminate between conventional adenoma and carcinoma can be used to predict the biological behaviour of these tumours. Adrenocortical adenomas generally weigh less than 100 g and measuring 7.5 cm or less in greatest diameter.9 Mitotic rates of three mitoses or fewer per 10 high-power fields (HPFs) are associated with adenomas. Necrosis and vascular invasion are absent in adenomas, and although they may have areas of capsular invasion, extensive extracapsular invasion is seen exclusively in carcinomas.10,11 The size and weight of the tumour in the present case were in the expected ranges for adenomas, as was the mitotic count. No necrosis or vascular invasion was observed in this case. The differential diagnosis of myxoid adrenocortical tumours includes metastatic carcinomas and primary retroperitoneal tumours with myxoid changes, such as, chordoma, myxoma, chondrosarcoma, lipoma, liposarcoma, leiomyoma, leiomyosarcoma, benign and malignant nerve sheath tumour, and malignant fibrous histiocytoma. The presence of foci of conventional
190
Pathology (2009), 41(2), February
CORRESPONDENCE
FIG. 3 (A) Anastomosing cords and pseudoglands of tumour cells floating loosely in the myxoid background (H&E, 6 200). (B) Histochemical stain for Alcian blue (pH 2.5) highlighting the abundance of myxoid material (Alcian blue pH 2.5, 6 200). TABLE 1
Clinicopathological features of myxoid adrenocortical adenomas Age/ Sex
Weight (g)
Size (cm)
21/F 35/F 31/F 73/M 16/F 62/F 56/M
72.2 13 37 43 – 106 –
7.5 3.5 6 4 7 6 3.2 6 3 6 2
5
45/M
58
Bollito et al.6
58/M
55
Our case
44/M
12
Cases Brown et al.3
Honda et al.4 Dundr et al.
Necrosis
Mitosis (/10 HPF)
Capsule invasion
95 40 70 50 80 40 66
No No No No No No No
3 0 2 0 1 1 0
No Focal Focal Focal Focal No –
490
No
0
No
564
475
No
3
No
2.7 6 2.7
490
No
0
No
5
Myxoid area (%)
Histological pattern
Immunohistochemistry
Anastomosing cord, nest, pseudoglandular
Inhibin (þ) in five cases Syn (þ) in six cases Vim (þ) in five cases CK Cam5.2 (þ) in one case
Anastomosing, microcystic, pseudoglandular Pseudoglandular, anastomosing cord, floating cluster Anastomosing cord, tubule, microcystic
Vim focal (þ) EMA, CK (–) Cam5.2, Syn weak (þ) CK AE1/AE3, EMA, CEA (–)
Anastomosing cord, nest, pseudoglandular
Vim, CK LMW, a-inhibin, Syn (þ); MUC1, EMA, S-100, CgA, SMA (–) Vim, Cam5.2 (þ) Syn focal weak (þ) CK, S-100, CgA, EMA (–)
CEA, carcinoembryonic antigen; CgA, chromogranin A; CK, cytokeratin; EMA, epithelial membrane antigen; LMW, low molecular weight; S-100, S-100 protein; Syn, synaptophysin; Vim, vimentin.
adrenocortical tumours in the myxoid neoplasm of the adrenal cortex is a helpful diagnostic feature. In addition, combined immunohistochemical analysis and/or ultrastructural studies could help to differentiate these lesions. Alcian blue staining has highlighted extracellular acidic mucosubstances in all reported myxoid adrenocortical adenomas. Brown et al.3 found synaptophysin positivity in all six cases examined, and positivity for vimentin and a-inhibin in five cases. Moreover, ultrastructural studies have revealed a welldeveloped rough and smooth endoplasmic reticulum consistent with an adrenal cortical origin.2,3
In this study, we describe an additional case of myxoid adrenocortical adenoma. The current case shared the histological features and immunophenotype of previously described cases. The gross and histological features of the present tumour match the criteria of conventional adenoma. Kyu Yun Jang* Myoung Ja Chung* Woo Sung Moon* Myoung Jae Kang* Dong Geun Lee* Ho Sung Park*
CORRESPONDENCE
Young Kon Kim{ Young Bum Jeong{ Departments of *Pathology, {Radiology, and {Urology, Institute for Medical Science, Center for Healthcare Technology Development, Chonbuk National University Medical School, Korea Professor H. S. Park. E-mail: [email protected]
ACKNOWLEDGEMENT This work was supported by a grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/ Center for Healthcare Technology Development).
1. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 2. Tang CK, Harriman BB, Toker C. Myxoid adrenal cortical carcinoma: a light and electron microscopic study. Arch Pathol Lab Med 1979; 103: 635–8. 3. Brown FM, Gaffey TA, Wold LE, Lloyd RV. Myxoid neoplasms of the adrenal cortex: a rare histologic variant. Am J Surg Pathol 2000; 24: 396–401. 4. Honda K, Kashima K, Daa T, Gamachi A, Nakayama I, Yokoyama S. Myxoid adrenal cortical adenoma. Pathol Int 2001; 51: 887–91. 5. Dundr P, Nova´k K. Pseudoglandular myxoid adenoma of the adrenal gland. Pathol Res Pract 2003; 199: 493–6. 6. Bollito ER, Papotti M, Porpiglia F, et al. Myxoid adrenocortical adenoma with a pseudoglandular pattern. Virchows Arch 2004; 445: 414–8. 7. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985; 64: 270–83. 8. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 9. Barnett CC, Varma DG, El-Naggar AK, et al. Limitations of size as a criterion in the evaluation of adrenal cortical tumors. Surgery 2000; 128: 973–82. 10. Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984; 8: 163–9. 11. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989; 13: 202–6.
DOI: 10.1080/00313020802579300
Does CD10 immunoexpression have a diagnostic utility in the differential diagnosis of renal oncocytomas and eosinophilic variants of chromophobe renal cell carcinomas? Sir, Nowadays, more renal tumours are detected incidentally due to the improvement in radiological modalities. As a result, surgeons require the distinction of eosinophilic variant of chromophobe renal cell carcinomas (RCCs) and renal oncocytomas (ROs) in Tru-cut biopsies for performing nephron sparing surgery. What is more, this distinction sometimes poses a diagnostic difficulty in H&E
191
sections. However, diffuse staining with Hale’s colloidal iron (HCI) stain and ultrastructural demonstration of chromophobe type microvesicles are still accepted as the most important criteria for the diagnosis of chromophobe RCCs.1 Although HCI staining plays an important role in the absence of some technical problems, it lacks sensitivity.1 On the other hand, ultrastructural studies cannot be performed easily. For this reason, many immunomarkers have been studied for the differential diagnosis between chromophobe RCCs and ROs in recent years. CD10, which is a cell surface metalloproteinase localised to the proximal nephron of the kidney, has been considered a useful marker in the differential diagnosis of RCC, because of its high level of expression in clear cell and papillary RCCs and its absence in chromophobe RCC.2–9 On the other hand, a number of studies have shown that CD10 is expressed in ROs and chromophobe RCCs.2,7,9,10 Recently, we have stated that apical and/or polar CD63 (a lysosomal membrane glycoprotein) immunostaining had 95% sensitivity and 100% specificity to diagnose ROs.1 However, the conflicting CD10 immunostaining results of previous studies led us to perform this study. We aimed to investigate the usefulness of CD10 and to compare it with CD63 in the differential diagnosis of ROs and eosinophilic variants of chromophobe RCCs. A total of 85 resected eosinophilic renal epithelial tumours (53 ROs and 32 eosinophilic variants of chromophobe RCCs) were included in this study. Routine immunohistochemical staining was performed on formalinfixed, paraffin-embedded tissues using the streptavidin– biotin complex method. The primary antibodies which were applied are as follows: anti-CD63 (monoclonal, mouse antihuman, clone NKI/C3, 1:100, 60 min; NeoMarkers, USA) and anti-CD10 antibodies (monoclonal, mouse antihuman, clone 56C6, 1:10, 120 min; Novocastra Laboratories, UK). The results of immunohistochemical staining were recorded as positive (410% of tumour cells staining) or negative, and when appropriate, the staining pattern (cytoplasmic diffuse, cytoplasmic apical and/or polar, cytoplasmic disperse-irregular and membranous) was noted. The results of the staining pattern are summarised in Table 1 (Fig. 1 and 2). TABLE 1 Cytoplasmic distribution of the immunoreactivities Renal oncocytomas n (%)
Chromophobe RCCs n (%)
Total CD63* No staining Diffuse Apical and/or polar Disperse-irregular Membranous
53 53 0 1 51 1 0
(100) (100) (0) (2) (96) (2) (0)
32 32 0 31 0 1 0
(100) (100) (0) (97) (0) (3) (0)
CD10* No staining Diffuse Focal cytoplasmic Disperse-irregular Membranous
12 41 7 4 1 0
(23) (77) (13) (8) (2) (0)
8 24 2 4 2 0
(25) (75) (6) (13) (6) (0)
*Number of cases which were positive out of total. RCCs, renal cell carcinomas.
Pathology (2009), 41(2), February
CORRESPONDENCE
whereas the patients with symptomatic infection represent only ‘the tip of the iceberg’.12 Obviously, there is a need to culture for C. difficile in order to increase sensitivity of laboratory diagnosis of CDAD and obtain isolates for further studies. However, as culture and identification take longer than 48 h, results may not be useful for making management decision, especially in case of rapidly progressive C. difficile infections. Also, culturing every faecal specimen will add significantly to the laboratory workload. One possible solution is to employ a two-step testing algorithm:13 all stool specimens are first screened using an immunoassay for glutamate dehydrogenase (GDH), an enzyme produced by all (toxigenic and non-toxigenic) strains of C. difficile. This assay has been shown to be very sensitive and a good screening test.13,14 Specimens negative for GDH are immediately reported as negative, and GDH-positive specimens are tested for the presence of toxin A and B and cultured for C. difficile. Isolates from GDH positive specimens that initially tested toxin-negative are tested again for toxin A and B, to confirm the presence of toxigenic strains. Fenner et al.14 used this algorithm and showed that a negative GDH screen allowed reliable exclusion of C. difficile, and only a small percentage of specimens (those GDH-positive and toxin-negative) needed to be cultured and isolates tested for toxin production. This approach provides the desired increase in sensitivity and specificity of laboratory diagnosis of CDAD and is cost-effective, as GDH test is less expensive than toxin tests and avoids routine culture for C. difficile great majority of stool specimens. Isolation and identification of C. difficile was once a routine procedure in clinical microbiology laboratories, but has been mostly replaced by rapid toxin tests. Consequently, clinical decisions and infection control measures are based on the results of tests less sensitive and specific than culture.1 Furthermore, without isolates which can be typed and analysed, correlation of epidemiological and clinical findings with the particular strains is impossible. It is now up to microbiologists to be innovative and implement diagnostic strategies for CDAD that will be rapid, reliable, and cost-effective and will also ensure isolates of C. difficile are available for early identification and analysis of hypervirulent strains. Every novice in the microbiology laboratory soon learns that ‘Microbiologists do it with culture . . .’. In the case of CDAD, so we should. A. Sasha Jaksic* Graeme R. Nimmo* Brian W. Dwyer{ *Division of Microbiology, Pathology Queensland—Central Laboratory, Queensland, {Infection Management Service, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia Contact Dr A. S. Jaksic. E-mail: [email protected]
1. Elliott B, Chang BJ, Golledge CL, Riley TV. Clostridium difficileassociated diarrhoea. Intern Med J 2007; 37: 561–8. 2. Kuijper EJ, Coignard B, Tull P, ESCMID Study Group for Clostridium difficile; EU Member States; European Centre for Diseases Prevention and Control. Emergence of Clostridium difficileassociated disease in North America and Europe. Clin Microbiol Infect 2006; (Suppl 6): 2–18.
3. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353: 2433–41. 4. Loo VG, Poirier L, Miller MA, et al. Predominantly clonal multiinstitutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353: 2442–9. 5. Gerding DN. New definitions will help, but cultures are critical for resolving unanswered questions about Clostridium difficile. Infect Control Hosp Epidemiol 2007; 28: 113–15, 2007. 6. Delmee M, Van Broeck J, Simon A, Janssens M, Avesani V. Laboratory diagnosis of Clostridium difficile-associated diarrhoea; a plea for culture. J Med Microbiol 2005; 54: 187–91. 7. Peterson LR, Manson RU, Paule SM, et al. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis 2007; 45: 1152–60. 8. Bartlett JG, Gerding DN. Clinical recognition and diagnosis of Clostridium difficile infection. Clin Infect Dis 2008; 46: S12–18. 9. Johal SS, Hammond J, Solomin K, James PD, Mahida YR. Clostrodium difficile associated diarrhoea in hospitalised patients: onset in the community and role of flexible sigmoidoscopy. Gut 2004; 53: 673–7. 10. Kim KH, Fekety R, Batts DH, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibioticassociated colitis. J Infect Dis 1981; 143: 42–50. 11. Riggs MM, Sethi AJ, Zabarsky TF, Eckstein EC, Jump RLP, Donskey CJ. Asymptomatic carriers are a potential source of transmission of epidemic and nonepidemic Clostridium difficile strains among LongTerm Care Facility residents. Clin Infect Dis 2007; 45: 992–8. 12. Muto CA. Asymptomatic Clostridium difficile colonisation: Is this the tip of another iceberg? Clin Infect Dis 2007; 45: 999–1000. 13. Ticehurst JR, Aird DZ, Dam LM, Borek AP, Hargrove JT, Carroll KC. Effective detection of toxigenic Clostridium difficile by a two-step algorithm including tests for antigen and cytotoxin. J Clin Microbiol 2006; 44: 1145–9. 14. Fenner L, Widmer AF, Goy G, Rudin S, Frei R. Rapid and reliable diagnostic algorithm for detection of Clostridium difficile. J Clin Microbiol 2008; 46: 328–30.
DOI: 10.1080/00313020802579235
Adrenocortical adenoma with unusual myxoid histological pattern: a case report Sir, Myxoid changes in adrenocortical neoplasms are extremely rare. They were originally described in carcinomas,1,2 and account for just 4.7% of 300 adrenocortical neoplasms in the only published series.3 Only nine adenomas with myxoid change have been reported.3–6 In this study, we describe an additional case of myxoid adrenocortical adenoma and include a review of the literature. A 44-year-old man was admitted to our hospital for the evaluation of an asymptomatic right adrenal mass detected incidentally 3 months previously. A physical examination of the abdomen was unremarkable, and laboratory findings were entirely normal except for microscopic haematuria. The patient underwent an endocrine evaluation, which included measurements of vanillylmandelic acid, homovanillic acid, epinephrine, norepinephrine, metanephrine, cortisol, 17ketosteroid, and 17-hydroxycorticoid levels, which showed no functional abnormalities. Tumour markers (carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, prostate-specific antigen) were within normal ranges. Turbo spin echo-T1 inversion recovery MRI demonstrated an oval-shaped, strongly hyperintense lesion in the right adrenal gland (Fig. 1). Laparoscopic adrenalectomy was performed, and on gross examination, the adrenal gland with attached fibroadipose tissue weighed
CORRESPONDENCE
12 g. On sectioning, the tumour was found to be 2.7 6 2.7 cm in size and was a well-circumscribed, yellowgreyish mass, with gelatinous areas admixed with whitish fibrous areas (Fig. 2). A rim of compressed adrenal tissue was also present in the mass periphery. Microscopically, the tumour was demarcated by an incomplete fibrous capsule at its periphery, in which partially atrophic adrenal gland parenchyma was found. More than 90% of the tumour mass was characterised by a myxoid background containing anastomosing cords, small nests, and pseudoglands of tumour cells that were floating loosely in an acellular myxoid background (Fig. 3A). Most of the tumour cells had regular nuclei with fine chromatin and sometimes visible nucleoli, and moderate amounts of eosinophilic cytoplasm. In limited areas, cell clusters with an amphophilic or clear vesicular cytoplasm resembling classical adrenocortical adenoma were observed. There were neither mitotic figures nor necrosis, and no evidence of vascular or capsular invasion. Diffuse histochemical staining for Alcian blue (pH
FIG. 1 Turbo spin echo-T1 inversion recovery MRI showing an ovalshaped, strong hyperintense lesion, measuring 2.5 cm in diameter, in the right adrenal gland (arrow).
FIG. 2 Cut surface of the resected adrenal mass showing a wellcircumscribed, glistening, yellowish mass. A centrally situated, whitish, scar-like area is also noted.
189
2.5) highlighted the abundance of myxoid material (Fig. 3B), which was negative for periodic acid-Schiff (PAS) and mucicarmine. Tumour cells showed immunohistochemical reactivity to vimentin and cytokeratin CAM5.2. Synaptophysin was focal, weakly positive. Cytokeratin AE1/AE3, chromogranin A, and epithelial membrane antigen (EMA) were negative. Two months after the operation, the patient remained in good condition with no signs or symptoms of tumour recurrence. Neoplasms arising from a mesodermal origin, such as liposarcoma, malignant fibrous histiocytoma, and malignant mesothelioma, can produce acidic mucopolysaccharides and show myxoid change. Although adrenal cortical tumours may be able to produce acidic mucopolysaccharides due to their mesodermal origin, myxoid tumours of the adrenal cortex are extremely rare. To the best of our knowledge, only nine cases of myxoid adrenocortical adenoma have been reported in the literature to date (Table 1).3–6 The pathogenesis of this tumour is not known. From the rare reported cases, Carney complex may be a possible underlying hereditary disease, since it is known to affect the adrenal gland and, above all, to be associated with myxoid tumours elsewhere in the body.7 A characteristic feature of these tumours is ample extracellular myxoid material, and the extent of these areas in reported cases ranges from 10% to more than 90%. The origin of myxoid material in these tumours is unknown, though it has been suggested that it might represent a degenerative process or be a product of tumour cells.8 However, this material has never been found in the cytoplasm of tumour cells, and thus, it is presumed to reflect a degenerative process rather than being a product of these cells. The architectural pattern of these tumours is variable, and includes irregular clusters, nests, anastomosing cords, and pseudoglands. The tumour cells themselves have moderate amounts of eosinophilic or slightly basophilic cytoplasm with only occasional clear cells. Occasionally it can be difficult to distinguish adrenal cortical adenoma and carcinoma, and furthermore, myxoid changes may be observed in both benign and malignant adrenocortical neoplasms. As myxoid adrenal cortical tumours are extremely rare, the usual histopathological features used to discriminate between conventional adenoma and carcinoma can be used to predict the biological behaviour of these tumours. Adrenocortical adenomas generally weigh less than 100 g and measuring 7.5 cm or less in greatest diameter.9 Mitotic rates of three mitoses or fewer per 10 high-power fields (HPFs) are associated with adenomas. Necrosis and vascular invasion are absent in adenomas, and although they may have areas of capsular invasion, extensive extracapsular invasion is seen exclusively in carcinomas.10,11 The size and weight of the tumour in the present case were in the expected ranges for adenomas, as was the mitotic count. No necrosis or vascular invasion was observed in this case. The differential diagnosis of myxoid adrenocortical tumours includes metastatic carcinomas and primary retroperitoneal tumours with myxoid changes, such as, chordoma, myxoma, chondrosarcoma, lipoma, liposarcoma, leiomyoma, leiomyosarcoma, benign and malignant nerve sheath tumour, and malignant fibrous histiocytoma. The presence of foci of conventional
190
Pathology (2009), 41(2), February
CORRESPONDENCE
FIG. 3 (A) Anastomosing cords and pseudoglands of tumour cells floating loosely in the myxoid background (H&E, 6 200). (B) Histochemical stain for Alcian blue (pH 2.5) highlighting the abundance of myxoid material (Alcian blue pH 2.5, 6 200). TABLE 1
Clinicopathological features of myxoid adrenocortical adenomas Age/ Sex
Weight (g)
Size (cm)
21/F 35/F 31/F 73/M 16/F 62/F 56/M
72.2 13 37 43 – 106 –
7.5 3.5 6 4 7 6 3.2 6 3 6 2
5
45/M
58
Bollito et al.6
58/M
55
Our case
44/M
12
Cases Brown et al.3
Honda et al.4 Dundr et al.
Necrosis
Mitosis (/10 HPF)
Capsule invasion
95 40 70 50 80 40 66
No No No No No No No
3 0 2 0 1 1 0
No Focal Focal Focal Focal No –
490
No
0
No
564
475
No
3
No
2.7 6 2.7
490
No
0
No
5
Myxoid area (%)
Histological pattern
Immunohistochemistry
Anastomosing cord, nest, pseudoglandular
Inhibin (þ) in five cases Syn (þ) in six cases Vim (þ) in five cases CK Cam5.2 (þ) in one case
Anastomosing, microcystic, pseudoglandular Pseudoglandular, anastomosing cord, floating cluster Anastomosing cord, tubule, microcystic
Vim focal (þ) EMA, CK (–) Cam5.2, Syn weak (þ) CK AE1/AE3, EMA, CEA (–)
Anastomosing cord, nest, pseudoglandular
Vim, CK LMW, a-inhibin, Syn (þ); MUC1, EMA, S-100, CgA, SMA (–) Vim, Cam5.2 (þ) Syn focal weak (þ) CK, S-100, CgA, EMA (–)
CEA, carcinoembryonic antigen; CgA, chromogranin A; CK, cytokeratin; EMA, epithelial membrane antigen; LMW, low molecular weight; S-100, S-100 protein; Syn, synaptophysin; Vim, vimentin.
adrenocortical tumours in the myxoid neoplasm of the adrenal cortex is a helpful diagnostic feature. In addition, combined immunohistochemical analysis and/or ultrastructural studies could help to differentiate these lesions. Alcian blue staining has highlighted extracellular acidic mucosubstances in all reported myxoid adrenocortical adenomas. Brown et al.3 found synaptophysin positivity in all six cases examined, and positivity for vimentin and a-inhibin in five cases. Moreover, ultrastructural studies have revealed a welldeveloped rough and smooth endoplasmic reticulum consistent with an adrenal cortical origin.2,3
In this study, we describe an additional case of myxoid adrenocortical adenoma. The current case shared the histological features and immunophenotype of previously described cases. The gross and histological features of the present tumour match the criteria of conventional adenoma. Kyu Yun Jang* Myoung Ja Chung* Woo Sung Moon* Myoung Jae Kang* Dong Geun Lee* Ho Sung Park*
CORRESPONDENCE
Young Kon Kim{ Young Bum Jeong{ Departments of *Pathology, {Radiology, and {Urology, Institute for Medical Science, Center for Healthcare Technology Development, Chonbuk National University Medical School, Korea Professor H. S. Park. E-mail: [email protected]
ACKNOWLEDGEMENT This work was supported by a grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/ Center for Healthcare Technology Development).
1. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 2. Tang CK, Harriman BB, Toker C. Myxoid adrenal cortical carcinoma: a light and electron microscopic study. Arch Pathol Lab Med 1979; 103: 635–8. 3. Brown FM, Gaffey TA, Wold LE, Lloyd RV. Myxoid neoplasms of the adrenal cortex: a rare histologic variant. Am J Surg Pathol 2000; 24: 396–401. 4. Honda K, Kashima K, Daa T, Gamachi A, Nakayama I, Yokoyama S. Myxoid adrenal cortical adenoma. Pathol Int 2001; 51: 887–91. 5. Dundr P, Nova´k K. Pseudoglandular myxoid adenoma of the adrenal gland. Pathol Res Pract 2003; 199: 493–6. 6. Bollito ER, Papotti M, Porpiglia F, et al. Myxoid adrenocortical adenoma with a pseudoglandular pattern. Virchows Arch 2004; 445: 414–8. 7. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985; 64: 270–83. 8. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 9. Barnett CC, Varma DG, El-Naggar AK, et al. Limitations of size as a criterion in the evaluation of adrenal cortical tumors. Surgery 2000; 128: 973–82. 10. Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984; 8: 163–9. 11. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989; 13: 202–6.
DOI: 10.1080/00313020802579300
Does CD10 immunoexpression have a diagnostic utility in the differential diagnosis of renal oncocytomas and eosinophilic variants of chromophobe renal cell carcinomas? Sir, Nowadays, more renal tumours are detected incidentally due to the improvement in radiological modalities. As a result, surgeons require the distinction of eosinophilic variant of chromophobe renal cell carcinomas (RCCs) and renal oncocytomas (ROs) in Tru-cut biopsies for performing nephron sparing surgery. What is more, this distinction sometimes poses a diagnostic difficulty in H&E
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sections. However, diffuse staining with Hale’s colloidal iron (HCI) stain and ultrastructural demonstration of chromophobe type microvesicles are still accepted as the most important criteria for the diagnosis of chromophobe RCCs.1 Although HCI staining plays an important role in the absence of some technical problems, it lacks sensitivity.1 On the other hand, ultrastructural studies cannot be performed easily. For this reason, many immunomarkers have been studied for the differential diagnosis between chromophobe RCCs and ROs in recent years. CD10, which is a cell surface metalloproteinase localised to the proximal nephron of the kidney, has been considered a useful marker in the differential diagnosis of RCC, because of its high level of expression in clear cell and papillary RCCs and its absence in chromophobe RCC.2–9 On the other hand, a number of studies have shown that CD10 is expressed in ROs and chromophobe RCCs.2,7,9,10 Recently, we have stated that apical and/or polar CD63 (a lysosomal membrane glycoprotein) immunostaining had 95% sensitivity and 100% specificity to diagnose ROs.1 However, the conflicting CD10 immunostaining results of previous studies led us to perform this study. We aimed to investigate the usefulness of CD10 and to compare it with CD63 in the differential diagnosis of ROs and eosinophilic variants of chromophobe RCCs. A total of 85 resected eosinophilic renal epithelial tumours (53 ROs and 32 eosinophilic variants of chromophobe RCCs) were included in this study. Routine immunohistochemical staining was performed on formalinfixed, paraffin-embedded tissues using the streptavidin– biotin complex method. The primary antibodies which were applied are as follows: anti-CD63 (monoclonal, mouse antihuman, clone NKI/C3, 1:100, 60 min; NeoMarkers, USA) and anti-CD10 antibodies (monoclonal, mouse antihuman, clone 56C6, 1:10, 120 min; Novocastra Laboratories, UK). The results of immunohistochemical staining were recorded as positive (410% of tumour cells staining) or negative, and when appropriate, the staining pattern (cytoplasmic diffuse, cytoplasmic apical and/or polar, cytoplasmic disperse-irregular and membranous) was noted. The results of the staining pattern are summarised in Table 1 (Fig. 1 and 2). TABLE 1 Cytoplasmic distribution of the immunoreactivities Renal oncocytomas n (%)
Chromophobe RCCs n (%)
Total CD63* No staining Diffuse Apical and/or polar Disperse-irregular Membranous
53 53 0 1 51 1 0
(100) (100) (0) (2) (96) (2) (0)
32 32 0 31 0 1 0
(100) (100) (0) (97) (0) (3) (0)
CD10* No staining Diffuse Focal cytoplasmic Disperse-irregular Membranous
12 41 7 4 1 0
(23) (77) (13) (8) (2) (0)
8 24 2 4 2 0
(25) (75) (6) (13) (6) (0)
*Number of cases which were positive out of total. RCCs, renal cell carcinomas.