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Thyroid transcription factor 1 expression in a case of renal collecting duct carcinoma
Human Pathology (2012) 43, 1153–1156
www.elsevier.com/locate/humpath
Correspondence
Thyroid transcription factor 1 expression in a case of renal collecting duct carcinoma To the Editor: We have read, with great interest, the article by Bishop et al [1], published in the January 2010 issue of Human Pathology assessing thyroid transcription factor 1 (TTF-1) and napsin A expression in 149 lung tumors; in 5 colonic, 31 pancreatic, and 17 breast adenocarcinomas; 38 malignant mesothelioma; 118 renal cell carcinomas; and 81 thyroid tumors. The authors found that all renal tumors are TTF-1 negative. TTF-1 is a 38-kD protein that regulates transcription of genes in the thyroid, lung, and diencephalons. It was initially considered a reliable marker for carcinoma of lung and thyroid origin. Subsequently, TTF-1 expression has been found in adenocarcinomas from a number of diverse sites including the endometrium, endocervix, ovary, breast, and colon, as well as in neuroendocrine tumors, especially small cell carcinomas from any site; in bladder urothelial carcinoma (UC); and in salivary gland tumors. However, there are no studies that have found TTF-1 expression in primary renal carcinoma.
We have recently observed 1 case of renal collecting duct carcinoma (CDC) with positive immunostaining for TTF-1 in 80% of tumor cells (Figure). This unexpected observation prompted us to examine the expression of this marker in 56 cases of kidney tumors including 24 clear cell carcinomas, 9 papillary carcinomas, 4 chromophobe carcinomas, 1 mucinous tubular carcinoma, 14 oncocytomas, and 4 UCs of the renal pelvis. Immunohistochemistry was performed on 4-µm sections using a mouse monoclonal antibody against TTF-1 (clone 8G7G3/1, 1:100; Dako, Carpinteria, CA). All cases were TTF-1 negative. CDC is a rare type of renal malignancy, and one of the major World Health Organization diagnostic criteria is the absence of UC of the renal pelvis. Morphological, antigenic, and cytogenetic similarities between CDC and UC of renal pelvis have been described, and this association reflects the common embryologic origin of collecting duct and urothelial cells because they are derived from progressive branching of the mesonephric duct [2]. The aberrant expression of TTF-1 in CDC could be explained by the similar expression in bladder UC, as has been described in 2 recent studies [3,4], or due to the clone used. In fact, the controversial results in the literature of immunohistochemical TTF-1 expression in nonpulmonary tumors are due to the different clones used (8G7G3/1 or SPT24). Nevertheless, Matoso et al [4] have demonstrated that both clones stained with similar intensity the same nonpulmonary tumors. To the best of our knowledge, this is the first case of primary renal carcinoma displaying TTF-1 expression. In conclusion, TTF-1 immunoreactivity in a metastatic carcinoma cannot, by itself, be used to exclude the possibility of a renal origin. Rachele Del Sordo MD Michele Giansanti MD Guido Bellezza MD Angelo Sidoni MD Institute of Pathologic Anatomy and Histology Medical School, University of Perugia Perugia, Italy
Fig. CDC shows intense nuclear immunoreactivity for TTF-1 (original magnification × 200). 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.humpath.2012.03.004
1154
References [1] Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. HUM PATHOL 2010;41:20-5. [2] Orsola A, Trias I, Raventós CX, et al. Renal collecting (Bellini) duct carcinoma displays similar characteristics to upper tract urothelial cell carcinoma. Urology 2005;65:59-64. [3] Fernandéz-Aceňero MJ, Córdova S, Santonja C. Aberrant TTF-1 expression in papillary high-grade urothelial neoplasm: case report and literature review. Rom J Morphol Embryol 2011;52: 171-4. [4] Matoso A, Singh K, Jacob R, et al. Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in pulmonary and non pulmonary primary tumors. Appl Immunohistochem Mol Morphol 2010;18:142-9.
Thyroid transcription factor 1 expression in a case of renal collecting duct carcinoma—Reply We thank Del Sordo, et al. for their interest in our article [1]. The authors report a renal collecting duct carcinoma (CDC) that was strongly and diffusely positive for thyroid transcription factor 1 (TTF-1); this would be the first reported primary renal carcinoma positive for this marker. CDC is a rare renal neoplasm, and due to its morphologic overlap with other malignancies, its diagnosis is often one of exclusion [2]. While urothelial carcinoma is its most common mimic, unsuspected metastases can also closely resemble CDC. As a result, in a case like the one presented it would be very important to rule out a metastatic lung carcinoma. No other immunohistochemical results are presented by Del Sordo, et al., but we believe that a PAX-8 immunostain in particular would be very helpful in this setting since this marker is consistently positive in CDC (staining 100% of cases in our cohort) [3] and negative in lung carcinoma [4,5]. As the authors correctly noted, while TTF-1 is a very specific marker for lung and thyroid carcinomas as well as neuroendocrine neoplasms, its expression has also been occasionally seen in carcinomas primary to other organs [6]. To address the expression of “lung markers” in renal CDC, we performed immunohistochemistry for TTF-1 and napsin A on a previously constructed tissue microarray [3] containing 18 cases of renal CDC. While napsin A expression was seen in 11/18 cases (61%) – not surprising given that the normal renal collecting ducts are positive – TTF-1 was completely negative in all cases. These findings support the use of TTF-1 in addressing the possibility of metastatic lung carcinoma in the setting of a napsin A-positive renal tumor, and suggest that the case Del Sordo, et al. reported, if it truly represents CDC, is an outlier. If there is any question about the diagnosis of CDC versus metastatic lung cancer, a PAX-8 immunostain should help resolve the issue.
Correspondence Justin A. Bishop MD Rajni Sharma PhD George J. Netto MD Peter B. Illei MD The Johns Hopkins School of Medicine Department of Pathology, Baltimore, MD, USA doi:10.1016/j.humpath.2012.03.005
References [1] Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. HUM PATHOL 2010;41:20-5. [2] Sringley JR, Delahunt B. Uncommon and recently described renal carcinomas. Mod Pathol 2009;22(Suppl 2):S2-23. [3] Albadine R, Schultz L, Illei P, et al. PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. Am J Surg Pathol 2010;34:965-9. [4] Nonaka D, Tang Y, Chiriboga L, et al. Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Mod Pathol 2008;21:192-200. [5] Ye J, Hameed O, Findeis-Hosey JJ, et al. Diagnostic utility of PAX8, TTF-1, and napsin A for discriminating metastatic carcinoma from primary adenocarcinoma of the lung. Biotech Histochem 2012;87:30-4. [6] Matoso A, Singh K, Jacob R, et al. Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in pulmonary and non pulmonary primary tumors. Appl Immunohistochem Mol Morphol 2010;18:142-9.
A distinctive translocation carcinoma of the kidney; “rosette forming,” t(6;11), HMB45-positive renal tumor: a histomorphologic, immunohistochemical, ultrastructural, and molecular genetic study of 4 cases To the Editor: We have read the interesting article of Petersson et al [1] in which they exhaustively study 4 cases of “rosetteforming” t(6;11), HMB45-positive renal tumors, a variant of traslocation-associated carcinoma of kidney. On histologic examination in 1 of the cases, the authors describe “branching and tubular structures, rimmed by one row of neoplastic cells with granular cytoplasms having the nuclei aligned on the basement membrane, giving these structures a resemblance to glandular epithelium (Figures 3,4,5). In serial cut sections, it was apparent that these branching and tubular structures opened into areas with pseudorosettes (Figure 7)." According to the authors, these branching tubular structures were a characteristic of a proportion of these tumors, and they had not been previously described in these neoplasms. Nevertheless, in a case that we had previously published, we also found branching tubular structures and microcysts lined by epithelioid cells with wide eosinophilic or clear cytoplasms. Within the lumina of the microcysts, small nodules of hyaline material surrounded by small cells with pycnotic nuclei and clear cytoplasms were also present (Fig. 1C in reference 2). In our opinion, the histologic images of the tubular structures with pseudorosettes reported by
www.elsevier.com/locate/humpath
Correspondence
Thyroid transcription factor 1 expression in a case of renal collecting duct carcinoma To the Editor: We have read, with great interest, the article by Bishop et al [1], published in the January 2010 issue of Human Pathology assessing thyroid transcription factor 1 (TTF-1) and napsin A expression in 149 lung tumors; in 5 colonic, 31 pancreatic, and 17 breast adenocarcinomas; 38 malignant mesothelioma; 118 renal cell carcinomas; and 81 thyroid tumors. The authors found that all renal tumors are TTF-1 negative. TTF-1 is a 38-kD protein that regulates transcription of genes in the thyroid, lung, and diencephalons. It was initially considered a reliable marker for carcinoma of lung and thyroid origin. Subsequently, TTF-1 expression has been found in adenocarcinomas from a number of diverse sites including the endometrium, endocervix, ovary, breast, and colon, as well as in neuroendocrine tumors, especially small cell carcinomas from any site; in bladder urothelial carcinoma (UC); and in salivary gland tumors. However, there are no studies that have found TTF-1 expression in primary renal carcinoma.
We have recently observed 1 case of renal collecting duct carcinoma (CDC) with positive immunostaining for TTF-1 in 80% of tumor cells (Figure). This unexpected observation prompted us to examine the expression of this marker in 56 cases of kidney tumors including 24 clear cell carcinomas, 9 papillary carcinomas, 4 chromophobe carcinomas, 1 mucinous tubular carcinoma, 14 oncocytomas, and 4 UCs of the renal pelvis. Immunohistochemistry was performed on 4-µm sections using a mouse monoclonal antibody against TTF-1 (clone 8G7G3/1, 1:100; Dako, Carpinteria, CA). All cases were TTF-1 negative. CDC is a rare type of renal malignancy, and one of the major World Health Organization diagnostic criteria is the absence of UC of the renal pelvis. Morphological, antigenic, and cytogenetic similarities between CDC and UC of renal pelvis have been described, and this association reflects the common embryologic origin of collecting duct and urothelial cells because they are derived from progressive branching of the mesonephric duct [2]. The aberrant expression of TTF-1 in CDC could be explained by the similar expression in bladder UC, as has been described in 2 recent studies [3,4], or due to the clone used. In fact, the controversial results in the literature of immunohistochemical TTF-1 expression in nonpulmonary tumors are due to the different clones used (8G7G3/1 or SPT24). Nevertheless, Matoso et al [4] have demonstrated that both clones stained with similar intensity the same nonpulmonary tumors. To the best of our knowledge, this is the first case of primary renal carcinoma displaying TTF-1 expression. In conclusion, TTF-1 immunoreactivity in a metastatic carcinoma cannot, by itself, be used to exclude the possibility of a renal origin. Rachele Del Sordo MD Michele Giansanti MD Guido Bellezza MD Angelo Sidoni MD Institute of Pathologic Anatomy and Histology Medical School, University of Perugia Perugia, Italy
Fig. CDC shows intense nuclear immunoreactivity for TTF-1 (original magnification × 200). 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.humpath.2012.03.004
1154
References [1] Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. HUM PATHOL 2010;41:20-5. [2] Orsola A, Trias I, Raventós CX, et al. Renal collecting (Bellini) duct carcinoma displays similar characteristics to upper tract urothelial cell carcinoma. Urology 2005;65:59-64. [3] Fernandéz-Aceňero MJ, Córdova S, Santonja C. Aberrant TTF-1 expression in papillary high-grade urothelial neoplasm: case report and literature review. Rom J Morphol Embryol 2011;52: 171-4. [4] Matoso A, Singh K, Jacob R, et al. Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in pulmonary and non pulmonary primary tumors. Appl Immunohistochem Mol Morphol 2010;18:142-9.
Thyroid transcription factor 1 expression in a case of renal collecting duct carcinoma—Reply We thank Del Sordo, et al. for their interest in our article [1]. The authors report a renal collecting duct carcinoma (CDC) that was strongly and diffusely positive for thyroid transcription factor 1 (TTF-1); this would be the first reported primary renal carcinoma positive for this marker. CDC is a rare renal neoplasm, and due to its morphologic overlap with other malignancies, its diagnosis is often one of exclusion [2]. While urothelial carcinoma is its most common mimic, unsuspected metastases can also closely resemble CDC. As a result, in a case like the one presented it would be very important to rule out a metastatic lung carcinoma. No other immunohistochemical results are presented by Del Sordo, et al., but we believe that a PAX-8 immunostain in particular would be very helpful in this setting since this marker is consistently positive in CDC (staining 100% of cases in our cohort) [3] and negative in lung carcinoma [4,5]. As the authors correctly noted, while TTF-1 is a very specific marker for lung and thyroid carcinomas as well as neuroendocrine neoplasms, its expression has also been occasionally seen in carcinomas primary to other organs [6]. To address the expression of “lung markers” in renal CDC, we performed immunohistochemistry for TTF-1 and napsin A on a previously constructed tissue microarray [3] containing 18 cases of renal CDC. While napsin A expression was seen in 11/18 cases (61%) – not surprising given that the normal renal collecting ducts are positive – TTF-1 was completely negative in all cases. These findings support the use of TTF-1 in addressing the possibility of metastatic lung carcinoma in the setting of a napsin A-positive renal tumor, and suggest that the case Del Sordo, et al. reported, if it truly represents CDC, is an outlier. If there is any question about the diagnosis of CDC versus metastatic lung cancer, a PAX-8 immunostain should help resolve the issue.
Correspondence Justin A. Bishop MD Rajni Sharma PhD George J. Netto MD Peter B. Illei MD The Johns Hopkins School of Medicine Department of Pathology, Baltimore, MD, USA doi:10.1016/j.humpath.2012.03.005
References [1] Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. HUM PATHOL 2010;41:20-5. [2] Sringley JR, Delahunt B. Uncommon and recently described renal carcinomas. Mod Pathol 2009;22(Suppl 2):S2-23. [3] Albadine R, Schultz L, Illei P, et al. PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. Am J Surg Pathol 2010;34:965-9. [4] Nonaka D, Tang Y, Chiriboga L, et al. Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Mod Pathol 2008;21:192-200. [5] Ye J, Hameed O, Findeis-Hosey JJ, et al. Diagnostic utility of PAX8, TTF-1, and napsin A for discriminating metastatic carcinoma from primary adenocarcinoma of the lung. Biotech Histochem 2012;87:30-4. [6] Matoso A, Singh K, Jacob R, et al. Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in pulmonary and non pulmonary primary tumors. Appl Immunohistochem Mol Morphol 2010;18:142-9.
A distinctive translocation carcinoma of the kidney; “rosette forming,” t(6;11), HMB45-positive renal tumor: a histomorphologic, immunohistochemical, ultrastructural, and molecular genetic study of 4 cases To the Editor: We have read the interesting article of Petersson et al [1] in which they exhaustively study 4 cases of “rosetteforming” t(6;11), HMB45-positive renal tumors, a variant of traslocation-associated carcinoma of kidney. On histologic examination in 1 of the cases, the authors describe “branching and tubular structures, rimmed by one row of neoplastic cells with granular cytoplasms having the nuclei aligned on the basement membrane, giving these structures a resemblance to glandular epithelium (Figures 3,4,5). In serial cut sections, it was apparent that these branching and tubular structures opened into areas with pseudorosettes (Figure 7)." According to the authors, these branching tubular structures were a characteristic of a proportion of these tumors, and they had not been previously described in these neoplasms. Nevertheless, in a case that we had previously published, we also found branching tubular structures and microcysts lined by epithelioid cells with wide eosinophilic or clear cytoplasms. Within the lumina of the microcysts, small nodules of hyaline material surrounded by small cells with pycnotic nuclei and clear cytoplasms were also present (Fig. 1C in reference 2). In our opinion, the histologic images of the tubular structures with pseudorosettes reported by