Calretinin

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Stains & CD markers
Calretinin

Author: Nick Baniak, M.D.

Editorial Board Members: Christian M. Schürch, M.D., Ph.D., Jefree J. Schulte, M.D.

Last author update: 22 July 2022

Last staff update: 22 July 2022

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Calretinin

Table of Contents

Cite this page: Baniak N. Calretinin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainscalretinin.html. Accessed December 21st, 2024.

Definition / general

Calcium binding protein (Hum Pathol 2003;34:994)

Essential features

Nuclear and cytoplasmic staining
Used primarily in the diagnosis of Hirschsprung disease and to confirm sex cord stromal or mesothelial lineage
Also positive in adrenal cortical lesions, mesonephric carcinoma, female adnexal tumor of probable Wolffian origin (FATWO) and STK11 adnexal tumor

Pathophysiology

29 kilodalton calcium binding protein of the calmodulin superfamily (Hum Pathol 2003;34:994)
Function is not clearly understood but it is thought to act as a buffer or sensor of intracellular calcium ions (Hum Pathol 2006;37:312, Hum Pathol 2003;34:994)

Interpretation

Nuclear and cytoplasmic (Mod Pathol 2007;20:248)

Uses by pathologists

Differentiate (as part of a panel) pleural mesothelioma (positive) from lung adenocarcinoma (negative) (Mod Pathol 2007;20:248, Indian J Pathol Microbiol 2021;64:655, Am J Surg Pathol 2003;27:150, Arch Pathol Lab Med 2018;142:89)
Differentiate (as part of a panel) peritoneal mesothelioma (positive) from ovarian serous carcinoma (negative); however, calretinin can stain a significant minority of serous carcinomas (Am J Surg Pathol 2007;31:1139, Am J Surg Pathol 1998;22:1203)
Confirm mesothelial origin in pleural or peritoneal specimens (Hum Pathol 2003;34:994)
Diagnosis of Hirschsprung disease (showing an absence of mucosal innervation) (Pediatr Dev Pathol 2021;24:19, Mod Pathol 2009;22:1379)
Differentiate (as part of a panel) adrenal cortical lesions (positive) from metastatic renal cell carcinoma (negative) (Am J Surg Pathol 2011;35:678)
Differentiate (as part of a panel) adrenal cortical lesions (positive) from pheochromocytoma (negative) (Am J Surg Pathol 2010;34:423)
Diagnosing (as part of panel) sex cord stromal tumors (ovarian and testis) (Hum Pathol 2003;34:994, Am J Surg Pathol 2021;45:1303, Hum Pathol 2005;36:195)
Used as part of a panel in diagnosing cervical mesonephric carcinoma (Am J Surg Pathol 2018;42:1596, Am J Surg Pathol 2001;25:379)
Used as part of a panel in the diagnosis of STK11 adnexal tumors and FATWO (Am J Surg Pathol 2021;45:1061, Mod Pathol 2020;33:734)
Differentiate schwannoma (positive) from neurofibroma (negative or focal) (Am J Clin Pathol 2004;122:552)

Microscopic (histologic) images

Contributed by Nick Baniak, M.D. and Sharon Bihlmeyer, M.D.

Sarcomatoid mesothelioma

Sarcomatoid mesothelioma (CK5)

Sarcomatoid mesothelioma (calretinin)

Ganglion cells in colon

No ganglion cells

Ovarian granulosa cell tumor (adult)

Virtual slides

Images hosted on other servers:

Pedunculated nodule in the upper cutaneous lip

Rectum of newborn with Hirschsprung

Calretinin (absence of ganglion cells)

Cytology images

Contributed by Nick Baniak, M.D.

Lung adenocarcinoma

Mesothelioma

Positive staining - normal

Mesothelial cells (Hum Pathol 2003;34:994)
CNS (neurons, granular cells, astrocytes, Purkinje cells) (Hum Pathol 2003;34:994, Hum Pathol 2006;37:312)
Leydig cells (Hum Pathol 2003;34:994)
Ovary (theca cells, granulosa cells) (Hum Pathol 2003;34:994)
Endometrial stromal cells (Hum Pathol 2003;34:994)
Breast luminal cells (weak) (Hum Pathol 2003;34:994)
Adrenal cortical cells and sustentacular cells (Hum Pathol 2003;34:994, Appl Immunohistochem Mol Morphol 2010;18:414)
Salivary gland serous cells (weak) (Hum Pathol 2003;34:994)
Colonic ganglion cells (Pediatr Dev Pathol 2021;24:19)
Adipocytes (Hum Pathol 2006;37:312)

Positive staining - disease

Mesothelioma (81 - 100%; 57% sarcomatoid) (Hum Pathol 2003;34:994, Mod Pathol 2007;20:248, Sci Rep 2021;11:12554, Indian J Pathol Microbiol 2021;64:655, Am J Clin Pathol 2008;130:771, Am J Surg Pathol 2007;31:1139, Hum Pathol 2019;92:48)
Adrenal cortical lesions:
- Adenoma (100%) (Hum Pathol 2003;34:994, Appl Immunohistochem Mol Morphol 2010;18:414)
- Carcinoma (50 - 80%) (Hum Pathol 2003;34:994, Am J Surg Pathol 2011;35:678)
Testicular sex cord stromal tumors:
- Leydig cell tumor (79 - 100%) (Hum Pathol 2003;34:994, Am J Surg Pathol 2021;45:1303)
- Juvenile granulosa cell tumors (86%) (Am J Surg Pathol 2021;45:1303)
- Large cell calcifying Sertoli cell tumors (50%) (Am J Surg Pathol 2021;45:1303)
- Adult granulosa cell tumors (50%) (Am J Surg Pathol 2021;45:1303)
- Sertoli cell tumors (44%) (Am J Surg Pathol 2021;45:1303)
Ovarian sex cord stromal tumors:
- Adult granulosa cell tumor (90%) (Hum Pathol 2005;36:195)
- Sertoli-Leydig cell tumor (57%) (Hum Pathol 2005;36:195)
Female adnexal tumor of probable Wolffian origin (40 - 57%) (Mod Pathol 2020;33:734, Arch Pathol Lab Med 2022;146:166)
STK11 adnexal tumor (100%) (Am J Surg Pathol 2021;45:1061)
Cervical mesonephric adenocarcinoma (50 - 88%) (Am J Surg Pathol 2018;42:1596, Am J Surg Pathol 2001;25:379)
Adenomatoid tumors (100%) (Appl Immunohistochem Mol Morphol 2012;20:173)
Ameloblastoma (90 - 94%) (Histopathology 2000;37:27, Appl Immunohistochem Mol Morphol 2014;22:762)
Keratocystic odontogenic tumor (80%) (Appl Immunohistochem Mol Morphol 2014;22:762)
Lipoma (96%) (Hum Pathol 2006;37:312)
Liposarcoma (97%) (Hum Pathol 2006;37:312)
Cardiac myxoma (74%) (Histol Histopathol 2001;16:1031)
Colonic medullary carcinoma (73%) (Hum Pathol 2009;40:398)
Schwannoma (96%) (Am J Clin Pathol 2004;122:552)

Negative staining

Note: calretinin is usually negative in the below entities, with variable, generally rare, positive cases (see percentages below)
Derm:
- Squamous cell carcinoma (19%) (Hum Pathol 2003;34:994)
- Malignant melanoma (14%) (Hum Pathol 2003;34:994)
Head and neck:
- Laryngeal squamous cell carcinoma (23%) (Hum Pathol 2003;34:994)
- Oral cavity, squamous cell carcinoma (22%) (Hum Pathol 2003;34:994)
- Adenomatoid odontogenic tumor (0%) (Appl Immunohistochem Mol Morphol 2014;22:762)
Thoracic:
- Lung small cell carcinoma (41 - 49%) (Hum Pathol 2003;34:994, Am J Surg Pathol 2003;27:150)
- Lung squamous cell carcinoma (22 - 34%) (Hum Pathol 2003;34:994, Am J Surg Pathol 2003;27:150)
- Lung adenocarcinoma (0 - 11%) (Am J Surg Pathol 2003;27:150, Hum Pathol 2003;34:1155)
- Thymic carcinoma (36%) (Hum Pathol 2003;34:1155)
- Thymoma (3%) (Hum Pathol 2003;34:1155)
Breast:
- Invasive mammary carcinoma of no special type (ductal carcinoma) (4%) (Hum Pathol 2003;34:994)
- Medullary carcinoma (44%) (Hum Pathol 2003;34:994)
- Mucinous carcinoma (11%) (Hum Pathol 2003;34:994)
- Papillary carcinoma (14%) (Hum Pathol 2003;34:994)
- Phyllodes tumor (23%) (Hum Pathol 2003;34:994)
Gynecologic:
- Ovarian endometrioid carcinoma (18 - 36%) (Hum Pathol 2003;34:994, Hum Pathol 2005;36:195)
- Ovarian serous carcinoma (10 - 45%) (Hum Pathol 2003;34:994, Am J Clin Pathol 2008;130:771, Am J Surg Pathol 2007;31:1139, Am J Surg Pathol 1998;22:1203)
- Ovarian microcystic stromal tumor (6%) (Am J Surg Pathol 2009;33:367)
- Ovarian fibroma - thecoma (14 - 33%) (Hum Pathol 2005;36:195)
- Squamous cell carcinoma (cervix, vulva, vagina) (10 - 18%) (Hum Pathol 2003;34:994)
- Endocervical adenocarcinoma (0%) (Am J Surg Pathol 2018;42:1596)
- Endometrial mesonephric-like carcinoma (0%) (Am J Surg Pathol 2018;42:1596)
- Endometrial endometrioid adenocarcinoma (7%) (Am J Surg Pathol 2018;42:1596)
- Endometrial serous carcinoma (9%) (Am J Surg Pathol 2018;42:1596)
- Endometrial clear cell carcinoma (14%) (Am J Surg Pathol 2018;42:1596)
- Endometrial carcinosarcoma (26%) (Am J Surg Pathol 2018;42:1596)
Gastrointestinal:
- Hepatocellular carcinoma (2%) (Hum Pathol 2003;34:994)
- Pancreatic adenocarcinoma (5%) (Hum Pathol 2003;34:994)
- Gastric adenocarcinoma (6%) (Hum Pathol 2003;34:994)
- Small intestine, adenocarcinoma (11%) (Hum Pathol 2003;34:994)
- Colonic adenocarcinoma (5 - 6%) (Hum Pathol 2003;34:994, Pathol Oncol Res 2016;22:725)
Genitourinary:
- Prostatic adenocarcinoma (7%) (Hum Pathol 2003;34:994)
- Renal cell carcinoma, clear cell type (3 - 10%) (Hum Pathol 2003;34:994, Appl Immunohistochem Mol Morphol 2010;18:414, Am J Surg Pathol 2011;35:678)
- Renal cell carcinoma, papillary type (10%) (Hum Pathol 2003;34:994)
- Urothelial carcinoma (5%) (Hum Pathol 2003;34:994)
- Testicular seminoma (9%) (Hum Pathol 2003;34:994)
- Testicular fibroma - thecoma (25%) (Am J Surg Pathol 2021;45:1303)
- Testicular myoid gonadal stromal tumor (0%) (Am J Surg Pathol 2021;45:1303)
- Rete testis adenocarcinoma (40%) (Am J Surg Pathol 2019;43:670)
Neuroendocrine:
- Paraganglioma (16 - 27%) (Hum Pathol 2003;34:994, Appl Immunohistochem Mol Morphol 2010;18:414)
- Pheochromocytoma (3%) (Hum Pathol 2003;34:994)
- Thyroid medullary carcinoma (30%) (Hum Pathol 2003;34:994)
CNS:
- Astrocytoma (28%) (Hum Pathol 2003;34:994)
- Ependymoma (7%) (Hum Pathol 2003;34:994)
- Glioblastoma multiforme (16%) (Hum Pathol 2003;34:994)
- Oligodendroglioma (17%) (Hum Pathol 2003;34:994)
Other:
- Desmoplastic small round cell tumor (19%) (Mod Pathol 2003;16:229)
- Neurofibroma (7%) (Am J Clin Pathol 2004;122:552)

Sample pathology report

Right pleura, core needle biopsy:
- Mesothelioma
- Immunohistochemistry performed shows the following staining profile in the lesional cells:
  - Positive: calretinin, WT1
  - Negative: TTF1, Claudin4

Board review style question #1

A pleural fluid specimen consists of abundant clusters of atypical cells. Pancytokeratin and WT1 stains are positive, while Claudin4 and BerEp4 are negative. The figure above shows a calretinin stain. What is the most appropriate statement?

The biomarker result is noncontributory due to a lack of specificity
The biomarker result is supportive of a lung adenocarcinoma
The biomarker result is supportive of a lung squamous cell carcinoma
The biomarker result is supportive of malignant mesothelioma

Board review style answer #1

D. The biomarker result is supportive of malignant mesothelioma

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