Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

Jihoon Chang; Soo-Hong Kim; Hye Sook Min; Hyun-Young Kim; Sung-Eun Jung; Kwi-Won Park; Seong-Cheol Lee

doi:10.13029/jkaps.2013.19.2.108

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Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

Jihoon Chang, M.D., Soo-Hong Kim, M.D., Hye Sook Min, M.D.^∗, Hyun-Young Kim, M.D., Sung-Eun Jung, M.D., Kwi-Won Park, M.D., Seong-Cheol Lee, M.D.

Journal of the Korean Association of Pediatric Surgeons 2013;19(2):108-121.
Published online: December 17, 2013

DOI: https://doi.org/10.13029/jkaps.2013.19.2.108

Department of Pediatric Surgery, Seoul National University Children's Hospital, Seoul, Korea

^∗Department of Pathology, Seoul National University Hospital, Seoul, Korea

Correspondence Seong-Cheol Lee, M.D. Department of Pediatric Surgery, Seoul National University Children's Hospital 101, Daehang-Ro Jongro-Gu, Seoul 110-744, Korea Tel : 02)2072-2338, Fax : 02)747-7730 E-mail: leesc@snu.ac.kr

• Received: September 27, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure.

The Kaplan-Meier survival curves between benign and malignant PHEO and aPGL (p = .007)

Table 1.

Immunohistochemical Panel

Table 1.
Antibody	Primary antibody^∗	Company	Dilution	Buffer(pH)^†	Target Stain^‡	Cutoff Values^§
Ki-67	mm	DAKO, Carpinteria, California, USA	1:200	CA (6)	N	> 2 %
p53	mm	DAKO	1:200	CA (6)	N	> 5 %
mdm-2	mm	Leica Biosystems, Heidelberg, Germany	1:100	EDTA (9)	N	> 50 %
mdm-2		Santa Cruz
p21	mm	biotechnology, Dallas,	1:200	CA (6)	N	> 10 %
		Texas, USA
		Spring Bioscience,
p27	rp	Pleasaton, California,	1:300	CA (6)	N	> 30 %
p27		USA
bcl-2	mm	DAKO	1:100	CA (6)	C	> 50 %
cyclin D1	rp	Santa Cruz biotechnology	1:100	CA (6)	N	> 5 %

^∗mm, mouse monoclonal; rp, rabbit polyclonal

^†CA, citric acid; EDTA, Ethylenediaminetetraacetic acid

^‡N, Nuclei stain; C, Cytoplasmic stain

^§indicates high proliferative group in Ki-67; otherwise indicates group showed over-expression

Table 2.

Clinical Information of the Patients with PHEO and aPGL

Table 2.
	Total (n=20)	PHEO (n=14)	aPGL (n=6)	P value
Age (months, mean±SD)	143.90 ±40.87	141.93 ±39.26	148.50 ±19.60	.775^∗
Gender (M : F)	15 : 5	9 : 5	6 : 0	.260^†
Location				.829^†
Right (%)	7 (35)	5 (35.7)	2 (33.3%)
Left (%)	6 (30)	5 (35.7)	1 (16.7%)
Bilateral (%)	7 (35)	4 (28.6)	3 (50.0%)
Greatest dimension (cm, mean±SD)	4.86 ±1.50	4.84 ±1.26	4.88 ±2.08	.966^†
Malignancy (%)	7 (35)	4 (28.6)	3 (50.0%)	.613^†
Hereditary Features (%)	4 (20)	4 (28.6)	0	.267^†
Chemotherapy (%)	2 (10)	0	2 (33.3%)	.079^†
Radiotherapy (%)	6 (30)	3 (21.4)	3 (50.0%)	.303^†
Follow-up(months, mean±SD)	97.25 ±55.67	95.64 ±37.03	101.00 ±90.47	.850^∗
Disease free survival (months, mean±SD)	82.20 ±58.25	82.43 ±43.86	81.67 ±88.82	.985^∗
Median survival (months, range)	86.20 (14-252)	86.50 (50-159)	82.50 (14-252)	NA^§

^∗Student's t-test

^†Fisher's exact test

^§Not applicable

Table 3.

Clinical Information of the Patients with Benign and Malignant Tumors^∗

Table 3.
	Benign (n=13)	Malignant (n=7)	P value
Age (months, mean±SD)	143.77 ± 46.25	144.14 ± 31.78	.983^†
Gender (M : F)	10 : 3	5 : 2	> .999^‡
Hereditary Features (%)	3 (23.1)	1 (14.3)	> .999^‡
Chemotherapy (%)	0	2 (28.6)	.111^‡
Radiotherapy (%)	0	6 (85.7)	< .001^‡
Location			.381^‡
Right (%)	5 (38.5)	2 (28.6)
Left (%)	5 (38.5)	1 (14.3)
Bilateral (%)	3 (23.1)	4 (57.1)
Greatest dimension (cm, mean±SD)	5.01 ± 1.55	4.57 ± 1.44	.547^†
Clinical manifestation
Hypertension (%)	10 (76.9)	4 (57.1)	.613^‡
Palpitation (%)	7 (53.8)	3 (42.9)	> .999^‡
Headache (%)	6 (46.2)	2 (28.6)	.642^‡
Diaphoresis (%)	7 (53.8)	2 (28.6)	.374^‡
Flushing (%)	9 (69.2)	2 (28.6)	.160^‡
Nausea, vomiting (%)	7 (53.8)	3 (42.9)	> .999^‡
Follow-up (months, mean±SD)	90.38 ± 39.48	110.00 ± 80.02	.467^†
Disease free survival (months, mean±SD)	90.38 ± 39.48	67.00 ± 84.92	.690^†
Median survival period (months, range)	93.00 (14-159)	80.00 (22-252)	NA^§

^∗Analysis of all patients with PHEO and aPGL

^†Student's t-test

^‡Fisher's exact test

^§Not applicable

Table 4.

Microscopic Features of Benign and Malignant Tumors^∗

Table 4.
	Benign (n=13)	Malignancy (n=7)	P value^†
Capsular invasion (n, %)	4 (30.8)	3 (42.9)	.651
Vascular invasion (n, %)	0	4 (57.1)	.007
Extension into adipose tissue (n, %)	1 (7.69)	4 (57.1)	.031
Presence of large nests (n, %)	7 (53.8)	1 (14.3)	.158
Central tumor necrosis (n, %)	6 (46.2)	5 (71.4)	>.999
High cellularity (n, %)	3 (23.1)	2 (28.6)	>.999
Tumor cell spindling (n, %)	8 (61.5)	1 (14.3)	.070
Cellular monotony (n, %)	3 (23.1)	1 (14.3)	>.999
Mitosis (n, %)	1 (7.69)	4 (57.1)	.031
Atypical mitosis (n, %)	1 (7.69)	2 (28.6)	.270
Nuclear pleomorphism (n, %)	4 (30.8)	0	.249
Nuclear hyperchromasia (n, %)	9 (69.2)	2 (28.6)	.160

^∗Analysis of all patients with PHEO and aPGL

^†Fisher's exact test

Table 5.

Microscopic Features of Benign and Malignant PHEO^∗

Table 5.
	Benign (n=10)	Malignancy (n=4)	P value^†
Capsular invasion (n, %)	3 (30)	2 (50)	.580
Vascular invasion (n, %)	0	3 (75)	.033
Extension into adipose tissue (n, %)	0	3 (75)	.003
Presence of large nests (n, %)	7 (70)	0	.023
Central tumor necrosis (n, %)	5 (50)	4 (100)	.089
High cellularity (n, %)	3 (30)	1 (25)	.857
Tumor cell spindling (n, %)	7 (70)	1 (25)	.139
Cellular monotony (n, %)	3 (30)	0	.234
Mitosis (n, %)	1 (10)	3 (75)	.019
Atypical mitosis (n, %)	0	1 (25)	.114
Nuclear pleomorphism (n, %)	3 (30)	0	.234
Nuclear hyperchromasia (n, %)	8 (80)	0	.008

^∗Analysis of patients with PHEO only

^†Fisher's exact test

Table 6.

Analysis of PASS Score and Pathologic Score between Benign and Malignant Tumor^∗

Table 6.
	Benign (n=13)	Malignancy (n=7)	P value
PASS Score (mean±SD)	6.00 ± 2.86	7.57 ± 3.36	.317^†
PASS ≥ 4 (n, %)	10 (76.9)	5 (71.4)	>.999^‡
PASS ≥ 6 (n, %)	8 (61.5)	5 (71.4)	>.999^‡
Pathologic Score (mean±SD)	0.31 ± 0.86	3.43 ± 2.57	.001^†
Score < 2 (n, %)	12 (92.3)	2 (28.5)	.007^§
Score ≥ 2 (n, %)	1 (7.7)	5 (71.4)

^∗Analysis of all patients with PHEO and aPGL

^†Student's t-test

^‡Mann-Whitney test

^§Fisher's exact test

Table 7.

Immunohistochemistry^∗

Table 7.
Antibody	Benign (n=13)	Malignancy (n=7)	P value^†
Ki-67 (n, %)	2 (15.4)	4 (57.1)	.122
p53 (n, %)	2 (15.4)	3 (42.9)	.290
bcl-2 (n, %)	8 (61.5)	4 (57.1)	>.999
mdm-2 (n, %)	2 (15.4)	3 (42.9)	.290
cyclin D1 (n, %)	0	0	>.999
p21 (n, %)	3 (23.1)	3 (42.9)	.613
p27 (n, %)	2 (15.4)	3 (42.9)	.290

^∗Number of cases above cutoff values which are listed in Table 1.

^†Fisher's exact test

REFERENCES

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3. Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, Jimenez C. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. Journal of Clinical Endocrinology & Metabolism 95(5):2023-2037. 2010.
4. Eisenhofer G, Bornstein SR, Brouwers FM, Cheung NK, Dahia PL, de Krijger RR, Giordano TJ, Greene LA, Goldstein DS, Lehnert H, Manger WM, Maris JM, Neumann HP, Pacak K, Shulkin BL, Smith DI, Tischler AS, Young WF Jr. Malignant pheochromocytoma: current status and initiatives for future progress. Endocr Relat Cancer 11(3):423-36. 2004.
5. Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer research 63(17):5615-5621. 2003.
6. Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol 26(5):551-66. 2002.
7. Strong VE, Kennedy T, Al-Ahmadie H, Tang L, Coleman J, Fong Y, Brennan M, Ghossein RA. Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery 143(6):759-68. 2008.
8. de Krijger RR, van der Harst E, van der Ham F, Stijnen T, Dinjens WN, Koper JW, Bruining HA, Lamberts SW, Bosman FT. Prognostic value of p53, bcl-2, and c-erbB-2 protein expression in phaeochromocytomas. The Journal of pathology 188(1):51-55. 1999.
9. August C, August K, Schroeder S, Bahn H, Hinze R, Baba HA, Kersting C, Buerger H. CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmeta-stasized sporadic pheochromocytomas. Modern pathology 17(9):1119-1128. 2004.
10. Lam KY, Lo CY, Wat NM, Luk JM, Lam KS. The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas. Journal of clinical pathology 54(6):443-448. 2001.
11. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. The Journal of Immunology 133(4):1710-1715. 1984.
12. Nagura S, Katoh R, Kawaoi A, Kobayashi M, Obara T, Omata K. Immunohistochemical estimations of growth activity to predict biological behavior of pheochromocytomas. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 12(12):1107. 1999.
13. Elder EE, Xu D, Höög A, Enberg U, Hou M, Pisa P, Gruber A, Larsson C, Bäckdahl M. KI-67 and hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma. Modern pathology 16(3):246-255. 2003.
14. Pinato DJ, Ramachandran R, Toussi STK, Vergine M, Ngo N, Sharma R, Lloyd T, Meeran K, Palazzo F, Martin N, Khoo B, Dina R, Tan TM. Immunohistochemical markers of the hypoxic response can identify malignancy in phaeochromocytomas and paragangliomas and optimize the detection of tumours with VHL germline mutations. British Journal of Cancer 2013;108:429-437.
15. Stojadinovic A, Ghossein RA, Hoos A, Nissan A, Marshall D, Dudas M, Cordon-Cardo C, Jaques DP, Brennan MF. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. Journal of Clinical Oncology 20(4):941-950. 2002.
16. Pham TH, Moir C, Thompson GB, Zarroug AE, Hamner CE, Farley D, van Heerden J, Lteif AN, Young WF Jr. Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center. Pediatrics 118(3):1109-1117. 2006.
17. Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP. PGL.NET network. The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 94(8):2817-2827. 2009.
18. McNicol AM. Differential diagnosis of pheochromocytomas and paragangliomas. Endocrine pathology 12(4):407-415. 2001.
19. Manger WM, Eisenhofer G. Pheochromocytoma: diagnosis and management update. Current hypertension reports 6(6):477-484. 2004.
20. Ayala-Ramirez M, Feng L, Johnson MM, Ejaz S, Habra MA, Rich T, Busaidy N, Cote GJ, Perrier N, Phan A, Patel S, Waguespack S, Jimenez C. Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab 96(3):717-725. 2011.
21. Tischler AS. Pheochromocytoma and extra-adrenal paraganglioma: updates. Arch Pathol Lab Med 132(8):1272-1284. 2008.
22. Wu D, Tischler AS, Lloyd RV, DeLellis RA, de Krijger R, van Nederveen F, Nosé V. Observer variation in the application of the Pheochromocytoma of the Adrenal Gland Scaled Score. The American journal of surgical pathology 33(4):599-608. 2009.
23. Pollard PJ, El-Bahrawy M, Poulsom R, Elia G, Killick P, Kelly G, Hunt T, Jeffery R, Seedhar P, Barwell J, Latif F, Gleeson MJ, Hodgson SV, Stamp GW, Tomlinson IP, Maher ER. Expression of HIF-1α, HIF-2α (EPAS1), and their target genes in paraganglioma and pheochromocytoma with VHL and SDH mutations. Journal of Clinical Endocrinology & Metabolism 91(11):4593-4598. 2006.
24. Ein SH, Pullerits J, Creighton R, Balfe JW. Pediatric pheochromocytoma. A 36-year review. Pediatr Surg Int 12(8):595-598. 1997.
25. Perel Y, Schlumberger M, Marguerite G, Alos N, Revillon Y, Sommelet D, De Lumley L, Flamant F, Dyon JF, Lutz P, Heloury H, Lemerle J. Pheochromocytoma and paraganglioma in children: a report of 24 cases of the French Society of Pediatric Oncology. Pediatr Hematol Oncol 14(5):413-422. 1997.
26. Reddy VS, O'Neill JA Jr, Ho GW 3rd, Neblett WW 3rd, Pietsch JB, Morgan WM 3rd, Goldstein RE. Twenty-five-year surgical experience with pheochromocytoma in children. Am Surg 66(12):1085-1092. 2000.

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Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

J Korean Assoc Pediatr Surg. 2013;19(2):108-121. Published online December 17, 2013

DOI: https://doi.org/10.13029/jkaps.2013.19.2.108

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Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

J Korean Assoc Pediatr Surg. 2013;19(2):108-121. Published online December 17, 2013

DOI: https://doi.org/10.13029/jkaps.2013.19.2.108

Figure

Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

Figure. The Kaplan-Meier survival curves between benign and malignant PHEO and aPGL (p = .007)

Figure.

Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

Table 1.

Immunohistochemical Panel

Antibody	Primary antibody^∗	Company	Dilution	Buffer(pH)^†	Target Stain^‡	Cutoff Values^§
Ki-67	mm	DAKO, Carpinteria, California, USA	1:200	CA (6)	N	> 2 %
p53	mm	DAKO	1:200	CA (6)	N	> 5 %
mdm-2	mm	Leica Biosystems, Heidelberg, Germany	1:100	EDTA (9)	N	> 50 %
mdm-2		Santa Cruz
p21	mm	biotechnology, Dallas,	1:200	CA (6)	N	> 10 %
		Texas, USA
		Spring Bioscience,
p27	rp	Pleasaton, California,	1:300	CA (6)	N	> 30 %
p27		USA
bcl-2	mm	DAKO	1:100	CA (6)	C	> 50 %
cyclin D1	rp	Santa Cruz biotechnology	1:100	CA (6)	N	> 5 %

Table 2.

Clinical Information of the Patients with PHEO and aPGL

	Total (n=20)	PHEO (n=14)	aPGL (n=6)	P value
Age (months, mean±SD)	143.90 ±40.87	141.93 ±39.26	148.50 ±19.60	.775^∗
Gender (M : F)	15 : 5	9 : 5	6 : 0	.260^†
Location				.829^†
Right (%)	7 (35)	5 (35.7)	2 (33.3%)
Left (%)	6 (30)	5 (35.7)	1 (16.7%)
Bilateral (%)	7 (35)	4 (28.6)	3 (50.0%)
Greatest dimension (cm, mean±SD)	4.86 ±1.50	4.84 ±1.26	4.88 ±2.08	.966^†
Malignancy (%)	7 (35)	4 (28.6)	3 (50.0%)	.613^†
Hereditary Features (%)	4 (20)	4 (28.6)	0	.267^†
Chemotherapy (%)	2 (10)	0	2 (33.3%)	.079^†
Radiotherapy (%)	6 (30)	3 (21.4)	3 (50.0%)	.303^†
Follow-up(months, mean±SD)	97.25 ±55.67	95.64 ±37.03	101.00 ±90.47	.850^∗
Disease free survival (months, mean±SD)	82.20 ±58.25	82.43 ±43.86	81.67 ±88.82	.985^∗
Median survival (months, range)	86.20 (14-252)	86.50 (50-159)	82.50 (14-252)	NA^§

Table 3.

Clinical Information of the Patients with Benign and Malignant Tumors^∗

	Benign (n=13)	Malignant (n=7)	P value
Age (months, mean±SD)	143.77 ± 46.25	144.14 ± 31.78	.983^†
Gender (M : F)	10 : 3	5 : 2	> .999^‡
Hereditary Features (%)	3 (23.1)	1 (14.3)	> .999^‡
Chemotherapy (%)	0	2 (28.6)	.111^‡
Radiotherapy (%)	0	6 (85.7)	< .001^‡
Location			.381^‡
Right (%)	5 (38.5)	2 (28.6)
Left (%)	5 (38.5)	1 (14.3)
Bilateral (%)	3 (23.1)	4 (57.1)
Greatest dimension (cm, mean±SD)	5.01 ± 1.55	4.57 ± 1.44	.547^†
Clinical manifestation
Hypertension (%)	10 (76.9)	4 (57.1)	.613^‡
Palpitation (%)	7 (53.8)	3 (42.9)	> .999^‡
Headache (%)	6 (46.2)	2 (28.6)	.642^‡
Diaphoresis (%)	7 (53.8)	2 (28.6)	.374^‡
Flushing (%)	9 (69.2)	2 (28.6)	.160^‡
Nausea, vomiting (%)	7 (53.8)	3 (42.9)	> .999^‡
Follow-up (months, mean±SD)	90.38 ± 39.48	110.00 ± 80.02	.467^†
Disease free survival (months, mean±SD)	90.38 ± 39.48	67.00 ± 84.92	.690^†
Median survival period (months, range)	93.00 (14-159)	80.00 (22-252)	NA^§

Table 4.

Microscopic Features of Benign and Malignant Tumors^∗

	Benign (n=13)	Malignancy (n=7)	P value^†
Capsular invasion (n, %)	4 (30.8)	3 (42.9)	.651
Vascular invasion (n, %)	0	4 (57.1)	.007
Extension into adipose tissue (n, %)	1 (7.69)	4 (57.1)	.031
Presence of large nests (n, %)	7 (53.8)	1 (14.3)	.158
Central tumor necrosis (n, %)	6 (46.2)	5 (71.4)	>.999
High cellularity (n, %)	3 (23.1)	2 (28.6)	>.999
Tumor cell spindling (n, %)	8 (61.5)	1 (14.3)	.070
Cellular monotony (n, %)	3 (23.1)	1 (14.3)	>.999
Mitosis (n, %)	1 (7.69)	4 (57.1)	.031
Atypical mitosis (n, %)	1 (7.69)	2 (28.6)	.270
Nuclear pleomorphism (n, %)	4 (30.8)	0	.249
Nuclear hyperchromasia (n, %)	9 (69.2)	2 (28.6)	.160

Table 5.

Microscopic Features of Benign and Malignant PHEO^∗

	Benign (n=10)	Malignancy (n=4)	P value^†
Capsular invasion (n, %)	3 (30)	2 (50)	.580
Vascular invasion (n, %)	0	3 (75)	.033
Extension into adipose tissue (n, %)	0	3 (75)	.003
Presence of large nests (n, %)	7 (70)	0	.023
Central tumor necrosis (n, %)	5 (50)	4 (100)	.089
High cellularity (n, %)	3 (30)	1 (25)	.857
Tumor cell spindling (n, %)	7 (70)	1 (25)	.139
Cellular monotony (n, %)	3 (30)	0	.234
Mitosis (n, %)	1 (10)	3 (75)	.019
Atypical mitosis (n, %)	0	1 (25)	.114
Nuclear pleomorphism (n, %)	3 (30)	0	.234
Nuclear hyperchromasia (n, %)	8 (80)	0	.008

Table 6.

Analysis of PASS Score and Pathologic Score between Benign and Malignant Tumor^∗

	Benign (n=13)	Malignancy (n=7)	P value
PASS Score (mean±SD)	6.00 ± 2.86	7.57 ± 3.36	.317^†
PASS ≥ 4 (n, %)	10 (76.9)	5 (71.4)	>.999^‡
PASS ≥ 6 (n, %)	8 (61.5)	5 (71.4)	>.999^‡
Pathologic Score (mean±SD)	0.31 ± 0.86	3.43 ± 2.57	.001^†
Score < 2 (n, %)	12 (92.3)	2 (28.5)	.007^§
Score ≥ 2 (n, %)	1 (7.7)	5 (71.4)

Table 7.

Immunohistochemistry^∗

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