Histopathology 2014, 65, 764–774. DOI: 10.1111/his.12487
Granular cell tumours of the colorectum: histopathological and immunohistochemical evaluation of 30 cases Jong-In Na,* Hye-Jeong Kim,* Jong-Jae Jung, Young Kim, Sung-Sun Kim, Jae-Hyuk Lee, Kyung-Hwa Lee & Jong-Tae Park1 Departments of Pathology, and 1Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea Date of submission 25 April 2014 Accepted for publication 23 June 2014 Published online Article Accepted 5 July 2014
Na J-I, Kim H-J, Jung J-J, Kim Y, Kim S-S, Lee J-H, Lee K-H, Park J-T (2014) Histopathology 65, 764–774
Granular cell tumours of the colorectum: histopathological and immunohistochemical evaluation of 30 cases Aims: Granular cell tumours (GCTs) are uncommon in the gastrointestinal tract, particularly in the colorectum. Herein, we report a series of 30 colorectal GCTs and discuss the properties of colorectal GCTs based on histopathological and immunohistochemical studies. Methods and results: Searching the surgical pathology files identified 30 cases of colorectal GCTs for 2005–2013. A broad panel of antibodies including neural and macrophage markers were used for immunohistochemical evaluation. Colorectal GCTs predominantly involved the right colon and showed increased nuclear atypia including nuclear pleomorphism and nuclear spindling. All 24 cases with mucosal tumour components had infiltrative growth
patterns within the mucosa. In all available cases, diffuse strong immunopositivity was observed for S100 and SOX10 of schwannian differentiation markers, as well as for CD68. Other neuronal lineage markers, including CD56, neuron-specific enolase, nestin, and synaptophysin showed consistently high expression rates. The immunohistochemical results are suggestive for a neural origin of GCTs. Conclusion: Histopathological and immunohistochemical features of colorectal GCTs were delineated in this large series of 30 colorectal GCTs. Although the incidence of GCTs is relatively low, clinicians and pathologists need to be aware of GCT in the differential diagnosis.
Keywords: colorectal neoplasms, gastrointestinal tract, granular cell tumour, immunohistochemistry
Introduction Granular cell tumours (GCTs) have been described as a benign neoplasm characterized by granular eosinophilic to lightly amphophilic cytoplasm.1,2 These tumours are found in various locations, including the Address for correspondence: K-H Lee, M.D., Ph.D. Department of Pathology, Chonnam National University Medical School, #5 Hakdong, Dong-gu, Gwangju 501-746, Korea. e-mail: mdkaylee@jnu. ac.kr and J-T Park, M.D., Ph.D. Department of Forensic Medicine, Chonnam National University Medical School, #5 Hak-dong, Donggu, Gwangju 501-746, Korea. e-mail: [email protected] *These authors contributed equally to this work. We authors certify that there is no conflict of interest regarding the materialdiscussed in the manuscript. © 2014 John Wiley & Sons Ltd.
tongue, subcutaneous tissues, and upper respiratory tract, but are uncommon in the gastrointestinal tract.1 In the gastrointestinal tract, they are preferentially found in the esophagus, followed by the colorectum and perianal region.2 These tumours lack specific clinical features and may present as incidental polyps or submucosal nodules.1 They have a low recurrence rate with adequate excision, but a few cases have been reported to be malignant with disseminated metastatic disease.3–5 The majority of clinicopathological data have been collected from the gastrointestinal tract on esophageal lesions, and only one large series of 26 colorectal GCTs has been reported.2 Nevertheless, additional features of these rare colorectal GCTs must be elucidated including their demographics,
Colorectal granular cell tumours
histopathological features, and immunohistochemical characteristics. Herein, we report a series of 30 colorectal GCTs and describe their histopathological features including the possible origin of colorectal GCTs based on immunohistochemistry.
765
was re-evaluated for cases showing disagreement between observers. Two pathologists reviewed the cases together and then reached an agreement for inconclusive samples.
Results Materials and methods The archives of the Departments of Pathology at Chonnam National University Hwasun Hospital (CNUHH), Chonnam National University Hospital (CNUH) and the Foryou Private Clinics were searched for GCTs of the colorectum during 2005–2013. A total of 30 GCTs of the colorectum were retrieved. The use of tumour tissue was approved by the local ethical committee (#CNUHH 2014-104). The cases were reviewed by two pathologists (KHJ and LKH) and assessed for the following: size, depth of involvement (mucosa or submucosa), mucosal and submucosal growth pattern (infiltrative versus marginating), nuclear pleomorphism, nuclear spindling, mucosal surface changes, intratumoral lymphoid aggregation, peritumoral lymphoid cuffs, hyalinization, focal calcification, and fat infiltration. Hyalinization was graded according to extent ( , none; +, mild; ++, moderate). Clinical records were reviewed (available in only six cases from CNUHH and CNUH) and presenting signs and symptoms, and the number of tumours were recorded. Blocks were available for immunohistochemistry in 30 cases. Sections were immunostained with specific antibodies against S100, CD68, CD163, inhibin-a, calretinin, CD57, CD56, synaptophysin, neuron-specific enolase (NSE), nestin, SOX10, CDX2, p53, and Ki-67. Table 1 shows the antibodies, their sources with code numbers and clonality, dilutions, and pretreatments. Automated immunohistochemical staining was performed using the Bond-max system (Leica Microsystems, Bannockburn, IL, USA), as described previously.6 Negative controls were treated similarly with the exception of primary antibodies. Positive controls were used for all markers as follows: S100, schwannoma; CD68 and CD163, macrophage; inhibin-a, Sertoli cell tumour; calretinin, mesothelioma; CD57, graft-versus-host disease; CD56, synaptophysin and NSE, carcinoid; nestin, glioblastoma; SOX10, melanoma; CDX2, colon adenocarcinoma; and p53 and ki-67, invasive ductal carcinoma. Immunoreactivity was graded according to staining intensity ( , negative; +, weak; ++, moderate; +++, strong) and extent (focal, 0.1 M
No
No
No
No
No
–
EB No Infiltrative – Cecum 46/M 21
>0.2 M
No
No
No
No
No
–
No
EMR Yes No – Yes No No Yes Marginating Focal – Cecum
0.3 SM
Mucosal growth pattern Size Location (cm) Depth Age/ Patient Sex
Table 2. (Continued)
Incomplete removal
J-I Na et al.
Submucosal Mucosal Intratumoral Peritumoral growth Nuclear Nuclear surface lymphoid lymphoid Focal Fat Sampling pattern pleomorphism spindling change aggregation cuffs Hyalinization calcification infiltration method Others
768
of the GCTs available for immunohistochemistry stained with CDX2. Of 28 cases available, nine (32%) were weakly positive for p53, and all cases showed Ki-67 labeling indices of far
Granular cell tumours of the colorectum: histopathological and immunohistochemical evaluation of 30 cases Jong-In Na,* Hye-Jeong Kim,* Jong-Jae Jung, Young Kim, Sung-Sun Kim, Jae-Hyuk Lee, Kyung-Hwa Lee & Jong-Tae Park1 Departments of Pathology, and 1Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea Date of submission 25 April 2014 Accepted for publication 23 June 2014 Published online Article Accepted 5 July 2014
Na J-I, Kim H-J, Jung J-J, Kim Y, Kim S-S, Lee J-H, Lee K-H, Park J-T (2014) Histopathology 65, 764–774
Granular cell tumours of the colorectum: histopathological and immunohistochemical evaluation of 30 cases Aims: Granular cell tumours (GCTs) are uncommon in the gastrointestinal tract, particularly in the colorectum. Herein, we report a series of 30 colorectal GCTs and discuss the properties of colorectal GCTs based on histopathological and immunohistochemical studies. Methods and results: Searching the surgical pathology files identified 30 cases of colorectal GCTs for 2005–2013. A broad panel of antibodies including neural and macrophage markers were used for immunohistochemical evaluation. Colorectal GCTs predominantly involved the right colon and showed increased nuclear atypia including nuclear pleomorphism and nuclear spindling. All 24 cases with mucosal tumour components had infiltrative growth
patterns within the mucosa. In all available cases, diffuse strong immunopositivity was observed for S100 and SOX10 of schwannian differentiation markers, as well as for CD68. Other neuronal lineage markers, including CD56, neuron-specific enolase, nestin, and synaptophysin showed consistently high expression rates. The immunohistochemical results are suggestive for a neural origin of GCTs. Conclusion: Histopathological and immunohistochemical features of colorectal GCTs were delineated in this large series of 30 colorectal GCTs. Although the incidence of GCTs is relatively low, clinicians and pathologists need to be aware of GCT in the differential diagnosis.
Keywords: colorectal neoplasms, gastrointestinal tract, granular cell tumour, immunohistochemistry
Introduction Granular cell tumours (GCTs) have been described as a benign neoplasm characterized by granular eosinophilic to lightly amphophilic cytoplasm.1,2 These tumours are found in various locations, including the Address for correspondence: K-H Lee, M.D., Ph.D. Department of Pathology, Chonnam National University Medical School, #5 Hakdong, Dong-gu, Gwangju 501-746, Korea. e-mail: mdkaylee@jnu. ac.kr and J-T Park, M.D., Ph.D. Department of Forensic Medicine, Chonnam National University Medical School, #5 Hak-dong, Donggu, Gwangju 501-746, Korea. e-mail: [email protected] *These authors contributed equally to this work. We authors certify that there is no conflict of interest regarding the materialdiscussed in the manuscript. © 2014 John Wiley & Sons Ltd.
tongue, subcutaneous tissues, and upper respiratory tract, but are uncommon in the gastrointestinal tract.1 In the gastrointestinal tract, they are preferentially found in the esophagus, followed by the colorectum and perianal region.2 These tumours lack specific clinical features and may present as incidental polyps or submucosal nodules.1 They have a low recurrence rate with adequate excision, but a few cases have been reported to be malignant with disseminated metastatic disease.3–5 The majority of clinicopathological data have been collected from the gastrointestinal tract on esophageal lesions, and only one large series of 26 colorectal GCTs has been reported.2 Nevertheless, additional features of these rare colorectal GCTs must be elucidated including their demographics,
Colorectal granular cell tumours
histopathological features, and immunohistochemical characteristics. Herein, we report a series of 30 colorectal GCTs and describe their histopathological features including the possible origin of colorectal GCTs based on immunohistochemistry.
765
was re-evaluated for cases showing disagreement between observers. Two pathologists reviewed the cases together and then reached an agreement for inconclusive samples.
Results Materials and methods The archives of the Departments of Pathology at Chonnam National University Hwasun Hospital (CNUHH), Chonnam National University Hospital (CNUH) and the Foryou Private Clinics were searched for GCTs of the colorectum during 2005–2013. A total of 30 GCTs of the colorectum were retrieved. The use of tumour tissue was approved by the local ethical committee (#CNUHH 2014-104). The cases were reviewed by two pathologists (KHJ and LKH) and assessed for the following: size, depth of involvement (mucosa or submucosa), mucosal and submucosal growth pattern (infiltrative versus marginating), nuclear pleomorphism, nuclear spindling, mucosal surface changes, intratumoral lymphoid aggregation, peritumoral lymphoid cuffs, hyalinization, focal calcification, and fat infiltration. Hyalinization was graded according to extent ( , none; +, mild; ++, moderate). Clinical records were reviewed (available in only six cases from CNUHH and CNUH) and presenting signs and symptoms, and the number of tumours were recorded. Blocks were available for immunohistochemistry in 30 cases. Sections were immunostained with specific antibodies against S100, CD68, CD163, inhibin-a, calretinin, CD57, CD56, synaptophysin, neuron-specific enolase (NSE), nestin, SOX10, CDX2, p53, and Ki-67. Table 1 shows the antibodies, their sources with code numbers and clonality, dilutions, and pretreatments. Automated immunohistochemical staining was performed using the Bond-max system (Leica Microsystems, Bannockburn, IL, USA), as described previously.6 Negative controls were treated similarly with the exception of primary antibodies. Positive controls were used for all markers as follows: S100, schwannoma; CD68 and CD163, macrophage; inhibin-a, Sertoli cell tumour; calretinin, mesothelioma; CD57, graft-versus-host disease; CD56, synaptophysin and NSE, carcinoid; nestin, glioblastoma; SOX10, melanoma; CDX2, colon adenocarcinoma; and p53 and ki-67, invasive ductal carcinoma. Immunoreactivity was graded according to staining intensity ( , negative; +, weak; ++, moderate; +++, strong) and extent (focal, 0.1 M
No
No
No
No
No
–
EB No Infiltrative – Cecum 46/M 21
>0.2 M
No
No
No
No
No
–
No
EMR Yes No – Yes No No Yes Marginating Focal – Cecum
0.3 SM
Mucosal growth pattern Size Location (cm) Depth Age/ Patient Sex
Table 2. (Continued)
Incomplete removal
J-I Na et al.
Submucosal Mucosal Intratumoral Peritumoral growth Nuclear Nuclear surface lymphoid lymphoid Focal Fat Sampling pattern pleomorphism spindling change aggregation cuffs Hyalinization calcification infiltration method Others
768
of the GCTs available for immunohistochemistry stained with CDX2. Of 28 cases available, nine (32%) were weakly positive for p53, and all cases showed Ki-67 labeling indices of far
