- Email: [email protected]
Aberrant immunohistochemical expression in infectious microorganisms
1052
Correspondence
as frequently malignant gastrinomas including 5 of 6 WDET (83%), and all 3 WDECs were negative for CC-3, this negative immunostaining may serve as a potential malignant marker in all PETs. Tatsuo Tomita MD Departments of Integrative Biosciences and Pathology and National Oregon Primate Center Oregon Health and Science University Portland, OR 97239, USA E-mail address: [email protected] doi:10.1016/j.humpath.2009.02.010
References [1] Cohen GM. Caspases: the excursions of apoptosis. Biochem J 1997; 326:1-16. [2] Hirata H, Takahashi A, Kobayashi S, et al. Caspases are activated in a branched protease cascade and control distinct downstream processes in Fas-induced apoptosis. J Exp Med 1998;187:587-600. [3] Butler AE, Jansen J, Bonner-Weir S, et al. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102-10. [4] Kloppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors. The WHO classification Ann NY Acad Sci 2004;1014:13-27. [5] Hruban RH, Pitna MB, Klimstra DS. Tumors of the pancreas. AFIP atlas of tumor pathology, 4. Washington, DC: AFIP; 2007. p. 251-304.
References [1] Delacruz V, Takahashi H, Nishida S, Tzakis A, Ruiz P. Segmental xanthomatosis of the small intestines. A case report and review of the literature. HUM PATHOL 2009;40:139-42. [2] Nielsen SL, Ingeholm P, Holck S, Talbot I. Xanthomatosis of the gastrointestinal tract with focus on small bowel involvement. J Clin Pathol 2007;60:1164-6 [Electronic publication 2006 June 23].
Intestinal xanthomatosis—reply To the Editor: We have read the article by Nielsen et al [1] published in The Journal of Clinical Pathology in October 2007. We agree that this article should be included in any review about intestinal xanthomatosis. The reason we did not include it in our survey was because our article, when originally submitted to another journal in August 2007, only included our literature survey from before June 2007. This article was not felt appropriate for that journal, and it was submitted thereafter to Human Pathology in 2007. Our article was ultimately published in January 2009 [2]. We apologize for this inadvertent omission of the article by Nielsen in our article. Victor Delacruz MD Phillip Ruiz MD, PhD E-mail address: [email protected]
Intestinal xanthomatosis To the Editor: With keen interest I read the recently published paper by Delacruz et al [1] on segmental xanthomatosis in which a small bowel example developed in the wake of radio-treating Ewing sarcoma is presented along with a review of previously reported cases of intestinal xanthomatosis in the English language literature. The authors consider intestinal xanthomatosis a nonspecific response to previous injury. Similar thoughts were expressed in a letter on intestinal xanthomatosis published October 2007 [2], suggesting that intestinal xanthomatosis is a result of an unusual reaction to various insults, iatrogenic or spontaneous. That letter presented an example of a transmural 15-cm-long xanthomatosis in an ischemic small bowel along with a review of the relevant literature. This case was, however, not included in the survey conducted by Delacruz et al [1]. Susanne Holck MD Faculty of Health Sciences Hvidovre University Hospital Copenhagen University Hvidovre, Denmark E-mail address: [email protected]
doi:10.1016/j.humpath.2009.03.001
doi:10.1016/j.humpath.2009.04.020
References [1] Nielsen SL, Ingeholm P, Holck S, Talbot I. Xanthomatosis of the gastrointestinal tract with focus on small bowel involvement. J Clin Pathol 2007;60:1164-6. [2] Delacruz V, Takahashi H, Nishida S, Tzakis A, Ruiz P. Segmental xanthomatosis of the small intestine. A case report and review of the literature. HUM PATHOL 2009;40:139-42.
Aberrant immunohistochemical expression in infectious microorganisms We read with interest the work by Sinelnikov et al [1], who first incidentally discovered consistent immunoreactivity for c-kit (CD117) of Giardia lamblia in duodenal biopsies performed to rule out mastocytosis. Based on this finding, the authors recommend to stain with CD117 all the duodenal biopsies performed with a suspicion of giardiasis. We would like to add here some further remarks on this issue. First, the finding of several CD117-positive mast cell in the lamina propria of duodenum may be of some alert in considering G lamblia infection given that mast cells seem to be important in the control of this infection [2].
Correspondence Second, although to us serial sections together with Giemsa stain are sufficient to highlight G lamblia even when microorganisms are few, we confirm the aberrant staining of this protozoan not only for CD117 (5/5 cases) (Fig. 1A) but also for other antibodies such as CD56 (3/5 cases) (Fig. 1B) and polyclonal CEA (3/5 cases), but not with CD34.
1053 However, we experienced aberrant expression of several antibodies in other infectious conditions, particularly when sustained by fungi. We noted this bizarre staining in 4 bronchial biopsies performed for primary lung cancer. Histology showed a poorly differentiated carcinoma (small cell carcinoma and squamous cell carcinomas in 2 cases each), but the biopsies also showed necrotic debris containing
Fig. 1 G lamblia microorganisms highlighted by CD117 (A) and CD56 (B). Bronchial biopsy with necrotic debris (C) comprising filamentous fungi morphologically consistent with Aspergillus species evidenced by methenamine silver stain (Grocott, D) but also immunoreacting with CD117 (E) and p63 (F).
1054
Correspondence
fungi (possibly Aspergillus species) (Fig. 1C) positively stained with Grocott methenamine silver stain (Fig. 1D), as well as CD117 (Fig. 1E), p63 (Fig. 1F), and chromogranin-A. Several articles have reported an inappropriate immunostaining (localization of the positive signal in a nonconventional subcellular structure) of different antibodies in many pathologic settings, also speculating on the diagnostic value of these aberrant expressions [3-5]. In conclusion, given that the exact mechanisms leading to this bizarre immunohistochemical results are unknown (possibly artifactual), we suggest some caution in using aberrant expression of immunostains with diagnostic intent. Hematoxylin-Eosin–based morphology coupled to more specific histochemical stains is preferable in highlight infectious agents in surgical pathology because infective pathogens of different nature may actually stain with several different antibodies. Giulio Rossi MD Annamaria Cadioli MD Alberto Cavazza MD Section of Pathologic Anatomy Azienda Policlinico 41100 Modena, Italy Operative Unit of Pathologic Anatomy Hospital St. Maria Nuova 42100 Reggio Emilia, Italy E-mail address: [email protected]
doi:10.1016/j.humpath.2009.03.009
References [1] Sinelnikov I, Sion-Vardy N, Shaco-Levy R. c-kit (CD117) immunostain is useful for the diagnosis of Giardia lamblia in duodenal biopsies. HUM PATHOL 2009;40:323-5. [2] Li E, Zhou P, Petrin Z, Singer SM. Mast cell-dependent control of Giardia lamblia infections in mice. Infect Immun 2004;72:6642-9. [3] Wieczorek TJ, Pinkus JL, Glickman JN, Pinkus GS. Comparison of thyroid transcription factor-1 and hepatocyte antigen immunohistochemical analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma. Am J Clin Pathol 2002;118:911-21. [4] Hirokawa M, Carney JA. Cell membrane and cytoplasmic staining for MIB-1 in hyalinizing trabecular adenoma of the thyroid gland. Am J Surg Pathol 2000;24:575-8. [5] Hattori H. Sclerosing hemangioma of the lung is positive for MIB-1 in cell membrane and cytoplasmic staining pattern. Histopathology 2002; 40:291-3.
Aberrant immunohistochemical expression in infectious microorganisms—reply To the Editor: Dr Rossi et al in their letter to the editor question our conclusion that c-kit (CD117) immunostain would be useful
in duodenal biopsies to confirm or exclude the possibility of giardiasis when there is a clinical or pathologic suspicion [1]. They assert that as the exact mechanism leading to Giardia lamblia immunoreactivity for c-kit is unknown, we should be cautious before using the immunoreactivity with diagnostic intent. Nevertheless, understanding the mechanisms of a specific immunoreactivity has never been required for such application. For example, calretinin is considered a sensitive marker for ovarian sex cord stromal tumors, although there has been no valid explanation [2]. Moreover, the articles Dr Rossi et al cite as if they were speculating on the diagnostic value of unexpected immunostaining in fact state their findings are useful [3-5]. For example, Hirokawa et al [3] could not explain why hyalinizing trabecular adenomas of the thyroid showed strong immunoreactivity for MIB-1 in their cell membrane and cytoplasm but concluded that this pattern typifies this benign tumor and therefore is useful in differentiating it from papillary carcinoma. Wieczorek et al [5], who reported on cytoplasmic immunoreactivity for thyroid transcription factor-1 (TTF-1) in hepatocellular carcinoma, concluded it is highly effective for distinguishing this tumor from other neoplasms, although the mechanism of this staining pattern remained without resolution. We showed consistent immunoreactivity of Giardia lamblia to c-kit in all of our cases. The consistency of this immunoreactivity was also evident in all of the authors' 5 cases. Moreover, the conspicuous and unique appearance shown by the protozoan to c-kit (staining of the paired nuclei and apical cellular membrane) is apparent in their picture as well. The result that Giardia lamblia is immunoreactive for CD56 and polyclonal Carcinoembryonic antigen (CEA) in 3 of 5 cases does not diminish the finding that it is 100% immunoreactive for c-kit. The authors describe 4 cases of bronchial biopsies where fungi were immunoreactive to c-kit, p63, and chromograninA. Because the appearance of the fungi stained with c-kit differs completely from the unique appearance of the Giardia lamblia, there should not be any confusion in making the correct diagnosis. Moreover, it emphasizes the need for further studies to determine immunoreactivity of other microorganisms to c-kit and other antibodies. We agree that a diagnosis should first be based on H and E morphology. The diagnosis of giardiasis may be challenging and special stains such as Giemsa may be helpful. However, as c-kit stains Giardia lamblia consistently and strongly and confers it a unique appearance, it is evidently useful and applicable in duodenal biopsies. Ruthy Shaco-Levy MD Igor Sinelnikov MD Netta Sion-Vardy MD Department of Pathology Soroka University Medical Center and Faculty of Health Sciences Ben-Gurion University of the Negev Beer-Sheva 84101, Israel
Correspondence
as frequently malignant gastrinomas including 5 of 6 WDET (83%), and all 3 WDECs were negative for CC-3, this negative immunostaining may serve as a potential malignant marker in all PETs. Tatsuo Tomita MD Departments of Integrative Biosciences and Pathology and National Oregon Primate Center Oregon Health and Science University Portland, OR 97239, USA E-mail address: [email protected] doi:10.1016/j.humpath.2009.02.010
References [1] Cohen GM. Caspases: the excursions of apoptosis. Biochem J 1997; 326:1-16. [2] Hirata H, Takahashi A, Kobayashi S, et al. Caspases are activated in a branched protease cascade and control distinct downstream processes in Fas-induced apoptosis. J Exp Med 1998;187:587-600. [3] Butler AE, Jansen J, Bonner-Weir S, et al. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102-10. [4] Kloppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors. The WHO classification Ann NY Acad Sci 2004;1014:13-27. [5] Hruban RH, Pitna MB, Klimstra DS. Tumors of the pancreas. AFIP atlas of tumor pathology, 4. Washington, DC: AFIP; 2007. p. 251-304.
References [1] Delacruz V, Takahashi H, Nishida S, Tzakis A, Ruiz P. Segmental xanthomatosis of the small intestines. A case report and review of the literature. HUM PATHOL 2009;40:139-42. [2] Nielsen SL, Ingeholm P, Holck S, Talbot I. Xanthomatosis of the gastrointestinal tract with focus on small bowel involvement. J Clin Pathol 2007;60:1164-6 [Electronic publication 2006 June 23].
Intestinal xanthomatosis—reply To the Editor: We have read the article by Nielsen et al [1] published in The Journal of Clinical Pathology in October 2007. We agree that this article should be included in any review about intestinal xanthomatosis. The reason we did not include it in our survey was because our article, when originally submitted to another journal in August 2007, only included our literature survey from before June 2007. This article was not felt appropriate for that journal, and it was submitted thereafter to Human Pathology in 2007. Our article was ultimately published in January 2009 [2]. We apologize for this inadvertent omission of the article by Nielsen in our article. Victor Delacruz MD Phillip Ruiz MD, PhD E-mail address: [email protected]
Intestinal xanthomatosis To the Editor: With keen interest I read the recently published paper by Delacruz et al [1] on segmental xanthomatosis in which a small bowel example developed in the wake of radio-treating Ewing sarcoma is presented along with a review of previously reported cases of intestinal xanthomatosis in the English language literature. The authors consider intestinal xanthomatosis a nonspecific response to previous injury. Similar thoughts were expressed in a letter on intestinal xanthomatosis published October 2007 [2], suggesting that intestinal xanthomatosis is a result of an unusual reaction to various insults, iatrogenic or spontaneous. That letter presented an example of a transmural 15-cm-long xanthomatosis in an ischemic small bowel along with a review of the relevant literature. This case was, however, not included in the survey conducted by Delacruz et al [1]. Susanne Holck MD Faculty of Health Sciences Hvidovre University Hospital Copenhagen University Hvidovre, Denmark E-mail address: [email protected]
doi:10.1016/j.humpath.2009.03.001
doi:10.1016/j.humpath.2009.04.020
References [1] Nielsen SL, Ingeholm P, Holck S, Talbot I. Xanthomatosis of the gastrointestinal tract with focus on small bowel involvement. J Clin Pathol 2007;60:1164-6. [2] Delacruz V, Takahashi H, Nishida S, Tzakis A, Ruiz P. Segmental xanthomatosis of the small intestine. A case report and review of the literature. HUM PATHOL 2009;40:139-42.
Aberrant immunohistochemical expression in infectious microorganisms We read with interest the work by Sinelnikov et al [1], who first incidentally discovered consistent immunoreactivity for c-kit (CD117) of Giardia lamblia in duodenal biopsies performed to rule out mastocytosis. Based on this finding, the authors recommend to stain with CD117 all the duodenal biopsies performed with a suspicion of giardiasis. We would like to add here some further remarks on this issue. First, the finding of several CD117-positive mast cell in the lamina propria of duodenum may be of some alert in considering G lamblia infection given that mast cells seem to be important in the control of this infection [2].
Correspondence Second, although to us serial sections together with Giemsa stain are sufficient to highlight G lamblia even when microorganisms are few, we confirm the aberrant staining of this protozoan not only for CD117 (5/5 cases) (Fig. 1A) but also for other antibodies such as CD56 (3/5 cases) (Fig. 1B) and polyclonal CEA (3/5 cases), but not with CD34.
1053 However, we experienced aberrant expression of several antibodies in other infectious conditions, particularly when sustained by fungi. We noted this bizarre staining in 4 bronchial biopsies performed for primary lung cancer. Histology showed a poorly differentiated carcinoma (small cell carcinoma and squamous cell carcinomas in 2 cases each), but the biopsies also showed necrotic debris containing
Fig. 1 G lamblia microorganisms highlighted by CD117 (A) and CD56 (B). Bronchial biopsy with necrotic debris (C) comprising filamentous fungi morphologically consistent with Aspergillus species evidenced by methenamine silver stain (Grocott, D) but also immunoreacting with CD117 (E) and p63 (F).
1054
Correspondence
fungi (possibly Aspergillus species) (Fig. 1C) positively stained with Grocott methenamine silver stain (Fig. 1D), as well as CD117 (Fig. 1E), p63 (Fig. 1F), and chromogranin-A. Several articles have reported an inappropriate immunostaining (localization of the positive signal in a nonconventional subcellular structure) of different antibodies in many pathologic settings, also speculating on the diagnostic value of these aberrant expressions [3-5]. In conclusion, given that the exact mechanisms leading to this bizarre immunohistochemical results are unknown (possibly artifactual), we suggest some caution in using aberrant expression of immunostains with diagnostic intent. Hematoxylin-Eosin–based morphology coupled to more specific histochemical stains is preferable in highlight infectious agents in surgical pathology because infective pathogens of different nature may actually stain with several different antibodies. Giulio Rossi MD Annamaria Cadioli MD Alberto Cavazza MD Section of Pathologic Anatomy Azienda Policlinico 41100 Modena, Italy Operative Unit of Pathologic Anatomy Hospital St. Maria Nuova 42100 Reggio Emilia, Italy E-mail address: [email protected]
doi:10.1016/j.humpath.2009.03.009
References [1] Sinelnikov I, Sion-Vardy N, Shaco-Levy R. c-kit (CD117) immunostain is useful for the diagnosis of Giardia lamblia in duodenal biopsies. HUM PATHOL 2009;40:323-5. [2] Li E, Zhou P, Petrin Z, Singer SM. Mast cell-dependent control of Giardia lamblia infections in mice. Infect Immun 2004;72:6642-9. [3] Wieczorek TJ, Pinkus JL, Glickman JN, Pinkus GS. Comparison of thyroid transcription factor-1 and hepatocyte antigen immunohistochemical analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma. Am J Clin Pathol 2002;118:911-21. [4] Hirokawa M, Carney JA. Cell membrane and cytoplasmic staining for MIB-1 in hyalinizing trabecular adenoma of the thyroid gland. Am J Surg Pathol 2000;24:575-8. [5] Hattori H. Sclerosing hemangioma of the lung is positive for MIB-1 in cell membrane and cytoplasmic staining pattern. Histopathology 2002; 40:291-3.
Aberrant immunohistochemical expression in infectious microorganisms—reply To the Editor: Dr Rossi et al in their letter to the editor question our conclusion that c-kit (CD117) immunostain would be useful
in duodenal biopsies to confirm or exclude the possibility of giardiasis when there is a clinical or pathologic suspicion [1]. They assert that as the exact mechanism leading to Giardia lamblia immunoreactivity for c-kit is unknown, we should be cautious before using the immunoreactivity with diagnostic intent. Nevertheless, understanding the mechanisms of a specific immunoreactivity has never been required for such application. For example, calretinin is considered a sensitive marker for ovarian sex cord stromal tumors, although there has been no valid explanation [2]. Moreover, the articles Dr Rossi et al cite as if they were speculating on the diagnostic value of unexpected immunostaining in fact state their findings are useful [3-5]. For example, Hirokawa et al [3] could not explain why hyalinizing trabecular adenomas of the thyroid showed strong immunoreactivity for MIB-1 in their cell membrane and cytoplasm but concluded that this pattern typifies this benign tumor and therefore is useful in differentiating it from papillary carcinoma. Wieczorek et al [5], who reported on cytoplasmic immunoreactivity for thyroid transcription factor-1 (TTF-1) in hepatocellular carcinoma, concluded it is highly effective for distinguishing this tumor from other neoplasms, although the mechanism of this staining pattern remained without resolution. We showed consistent immunoreactivity of Giardia lamblia to c-kit in all of our cases. The consistency of this immunoreactivity was also evident in all of the authors' 5 cases. Moreover, the conspicuous and unique appearance shown by the protozoan to c-kit (staining of the paired nuclei and apical cellular membrane) is apparent in their picture as well. The result that Giardia lamblia is immunoreactive for CD56 and polyclonal Carcinoembryonic antigen (CEA) in 3 of 5 cases does not diminish the finding that it is 100% immunoreactive for c-kit. The authors describe 4 cases of bronchial biopsies where fungi were immunoreactive to c-kit, p63, and chromograninA. Because the appearance of the fungi stained with c-kit differs completely from the unique appearance of the Giardia lamblia, there should not be any confusion in making the correct diagnosis. Moreover, it emphasizes the need for further studies to determine immunoreactivity of other microorganisms to c-kit and other antibodies. We agree that a diagnosis should first be based on H and E morphology. The diagnosis of giardiasis may be challenging and special stains such as Giemsa may be helpful. However, as c-kit stains Giardia lamblia consistently and strongly and confers it a unique appearance, it is evidently useful and applicable in duodenal biopsies. Ruthy Shaco-Levy MD Igor Sinelnikov MD Netta Sion-Vardy MD Department of Pathology Soroka University Medical Center and Faculty of Health Sciences Ben-Gurion University of the Negev Beer-Sheva 84101, Israel