© 2013 APMIS. Published by John Wiley & Sons Ltd. DOI 10.1111/apm.12205
APMIS 122: 657–659
Case Report
Inflammatory myofibroblastic tumor of the appendix arising after treatment of gastric cancer: a case report and review of the literature EUNJI OH,1 JAE Y. RO,2 JERAD M. GARDNER,3 JONG WON KIM,4 WOO-HEE JUNG1 and SUN OCH YOON1 1 Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Department of Pathology and Genomic Medicine, The Methodist Hospital, Weill Medical College of Cornel University, Houston, TX, USA; 3Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 4Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Oh EJ, Ro JY, Gardner JM, Kim JW, Jung W-H, Yoon SO. Inflammatory myofibroblastic tumor of the appendix arising after treatment of gastric cancer: a case report and review of the literature. APMIS 2014; 122: 657–659. Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue neoplasm of uncertain malignant potential and unclear etiology. IMT involving the appendix is very rare. Herein, we report a case of IMT of the appendix in a gastric cancer patient who was treated with radical gastrectomy and adjuvant systemic chemotherapy. Rare cases of IMT associated with preceding events have been described in other organs/sites, but not in the appendix. A previous intra-abdominal operation for gastric cancer may contribute to the development of IMT in the appendix as seen in the present patient. To our knowledge, this is the first case of appendiceal IMT arising after a previous operation. Key words: Inflammatory myofibroblastic tumor; appendix; surgery. Sun Och Yoon, MD, PhD, Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 135-720, Korea, e-mail: [email protected]
Inflammatory myofibroblastic tumor (IMT) is a rare tumor with unclear etiology and primarily occurs in children and young adults. Common sites include the lung, mesentery, and omentum (1, 2). IMT involving the appendix is very rare, and about 10 cases have been reported in the literature (3–6). Rare cases of IMT associated with preceding events have been described in other organs/sites (7–10), but not in the appendix. Herein, we report a first case of appendiceal IMT associated with previous intra-abdominal surgery. An 85-year-old male patient who had a history of gastric cancer presented with an incidental appendiceal mass detected on an imaging study. Total gastrectomy and systemic adjuvant chemotherapy with oral 5-fluorouracil (S1) for gastric ade-
Received 10 March 2013. Accepted 30 August 2013
nocarcinoma were performed 3 years and 5 months before the appendiceal mass was found. The resected appendix was tumorous and enlarged, measuring 10 9 5 9 4.5 cm (Fig. 1A). The cut surface of the appendix was fleshy and slightly myxoid (Fig. 1B). On microscopic examination, normal appendiceal tissue was replaced by proliferation of spindle cells in a collagenous and slightly myxoid background with scattered blood vessels (Fig. 1C). Plate-like collagen was seen focally (Fig. 1D), and the lymphoplasmacytic inflammatory infiltrate was relatively sparse. The proliferative spindle cells displayed bland cytology with low mitotic count (about 1/10 high power fields) and no necrosis. The external surface of the appendix was partly accompanied by fibrous adhesions with dense inflammatory cell infiltrates (Fig. 1E). Immunostains on spindle cells were positive for vimentin and smooth muscle actin (Fig. 1F 657
OH et al.
A
B
C
D
E
F
G
H
Fig 1. Gross photograph and microscopic and immunohistochemical findings of the appendix. (A) The appendix is tumorous, enlarged, and dilated at the distal portion with a tadpole appearance, measuring 10 9 594.5 cm. (B) The cut surface is fleshy, myxoid, and tan-gray with a partly mucinous component. (C) Spindle-or stellate-shaped cells are arranged in a fascicular pattern in the collagenous and slightly myxoid background with scattered blood vessels (9100). (D) Plate-like thick collagens are scattered in some areas (9100). (E) The lymphoplasmacytic infiltration is partly dense with serosal involvement (940). (F) Smooth muscle actin is expressed in approximately half of spindled tumor cells (9100). (G) Vimentin shows strong and diffuse cytoplasmic immunoreactivity in spindle tumor cells (9100). (H) MUC4 is negative (940).
and G) and negative for S100 protein, ALK, c-kit, desmin, CD21, CD23, and CD35. These immunostaining results support the myofibroblastic and fibroblastic differentiation of the tumor cells. In addition, MUC4 (Fig. 1H) and FISH for translocation t (7:16) (q34: p11) were performed to exclude the possibility of low-grade fibromyxoid sarcoma (LGFMS) and were negative. Ki-67 proliferation index was low (2%), and p53 immunoexpression was not observed. The patient has been in good health with no evidence of recurrence or metastasis at 1-year follow-up after appendectomy. The present appendiceal tumor was finally diagnosed as inflammatory myofibroblastic tumor rather than LGFMS, low-grade myxofibrosarcoma, or inflammatory pseudotumor-like variant of follicular dendritic cell sarcoma. The diagnosis was based on the previously described histologic fea-
tures, immunohistochemical findings, and molecular studies. The negative ALK immunostaining does not preclude a diagnosis of IMT. In fact, many studies have demonstrated that ALK alterations are detectable in only about 50% of IMTs (1). The etiology of IMT is unclear, but infectious, inflammatory, and immunologic responses have been considered as possible etiologies (11). In rare cases as shown in Table 1, it has been described as associated with trauma (7), neoplasia (8, 9), and previous surgery (10). IMTs in these cases arose 4 months to 9 years after the associated event. In our case, the appendiceal IMT developed 3 years and 5 months after intra-abdominal surgery, and no other possible causes were identified. We speculate that the previous intra-abdominal operation may have contributed to the development of the tumor in this patient. Exposure of the intra-abdom-
Table 1. Previously reported cases of inflammatory myofibroblastic tumor (IMT) after a preceding event Age/sex Etiology Site of IMT Breast parenchyma Case 1 (7) 22/M Trauma (direct blow; fall of a heavy object on the same site of the breast) Case 2 (8) 15/M Neoplasm (Wilms tumor of Upper abdomen involving right kidney) gastroesophageal junction, stomach, and liver Case 3 (9) 3.5/M Neoplasm (Wilms tumor of Liver right kidney) Case 4 (10) 2.5/M Previous surgery (Left Bladder, left inguinal region, herniorrhaphy) and left rectus abdominis muscle
658
Interval duration 4 months 9 years 18 months 28 months
© 2013 APMIS. Published by John Wiley & Sons Ltd
PSEUDOTUMOR OF THE APPENDIX
inal environment to an aggressive gastric cancer or subsequent systemic chemotherapy-associated inflammatory reaction may be other possible contributing factors. To our knowledge, this may be the first case of appendiceal IMT arising after a preceding event.
DISCLOSURE
5.
6.
7.
The authors have no relevant commercial or financial conflicts of interest to declare.
REFERENCES 1. Fletcher CDM, Unni KK, Mertens F, World Health Organization. International Agency for Research on C. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002. 2. Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995;19:859–72. 3. Uludag M, Citgez B, Polat N. Inflammatory pseudotumour of the appendix and acute appendicitis: a case report. Acta Chir Belg 2008;108:451–3. 4. Majumdar K, Sakhuja P, Kaur S, Rastogi A, Gondal R, Agarwal A. Inflammatory myofibroblastic tumor appendix with concomitant mucosal dysplasia, simu-
© 2013 APMIS. Published by John Wiley & Sons Ltd
8.
9.
10.
11.
lating pseudomyxoma on preoperative aspiration cytology. J Cancer Res Ther 2012;8:317–9. Bronzino P, Abbo L, Bagnasco F, Barisone P, Dezzani C, Genovese AM, et al. Intra-abdominal inflammatory myofibroblastic pseudotumor: case report and review of the literature. G Chir 2005;26:362–4. Bonnet JP, Basset T, Dijoux D. Abdominal inflammatory myofibroblastic tumors in children: report of an appendiceal case and review of the literature. J Pediatr Surg 1996;31:1311–4. Vecchio GM, Amico P, Grasso G, Vasquez E, La Greca G, Magro G. Post-traumatic inflammatory pseudotumor of the breast with atypical morphological features: a potential diagnostic pitfall. Report of a case and a critical review of the literature. Pathol Res Pract 2011;207:322–6. Vujanic GM, Milovanovic D, Aleksandrovic S. Aggressive inflammatory pseudotumor of the abdomen 9 years after therapy for Wilms tumor. A complication, coincidence, or association? Cancer 1992;70:2362–6. Newbould MJ, Kelsey A, Lendon M, Gururangan S. Inflammatory pseudotumor of the liver masquerading as a metastasis in a child treated for nephroblastoma. Med Pediatr Oncol 1992;20:172–5. Freud E, Bilik R, Yaniv I, Horev G, Cohen D, Mimouni M, et al. Inflammatory pseudotumor in childhood. A diagnostic and therapeutic dilemma. Arch Surg 1991;126:653–5. Saleem MI, Ben-Hamida MA, Barrett AM, Bunn SK, Huntley L, Wood KM, et al. Lower abdominal inflammatory myofibroblastic tumor -an unusual presentation- a case report and brief literature review. Eur J Pediatr 2007;166:679–83.
659
APMIS 122: 657–659
Case Report
Inflammatory myofibroblastic tumor of the appendix arising after treatment of gastric cancer: a case report and review of the literature EUNJI OH,1 JAE Y. RO,2 JERAD M. GARDNER,3 JONG WON KIM,4 WOO-HEE JUNG1 and SUN OCH YOON1 1 Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Department of Pathology and Genomic Medicine, The Methodist Hospital, Weill Medical College of Cornel University, Houston, TX, USA; 3Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 4Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Oh EJ, Ro JY, Gardner JM, Kim JW, Jung W-H, Yoon SO. Inflammatory myofibroblastic tumor of the appendix arising after treatment of gastric cancer: a case report and review of the literature. APMIS 2014; 122: 657–659. Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue neoplasm of uncertain malignant potential and unclear etiology. IMT involving the appendix is very rare. Herein, we report a case of IMT of the appendix in a gastric cancer patient who was treated with radical gastrectomy and adjuvant systemic chemotherapy. Rare cases of IMT associated with preceding events have been described in other organs/sites, but not in the appendix. A previous intra-abdominal operation for gastric cancer may contribute to the development of IMT in the appendix as seen in the present patient. To our knowledge, this is the first case of appendiceal IMT arising after a previous operation. Key words: Inflammatory myofibroblastic tumor; appendix; surgery. Sun Och Yoon, MD, PhD, Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 135-720, Korea, e-mail: [email protected]
Inflammatory myofibroblastic tumor (IMT) is a rare tumor with unclear etiology and primarily occurs in children and young adults. Common sites include the lung, mesentery, and omentum (1, 2). IMT involving the appendix is very rare, and about 10 cases have been reported in the literature (3–6). Rare cases of IMT associated with preceding events have been described in other organs/sites (7–10), but not in the appendix. Herein, we report a first case of appendiceal IMT associated with previous intra-abdominal surgery. An 85-year-old male patient who had a history of gastric cancer presented with an incidental appendiceal mass detected on an imaging study. Total gastrectomy and systemic adjuvant chemotherapy with oral 5-fluorouracil (S1) for gastric ade-
Received 10 March 2013. Accepted 30 August 2013
nocarcinoma were performed 3 years and 5 months before the appendiceal mass was found. The resected appendix was tumorous and enlarged, measuring 10 9 5 9 4.5 cm (Fig. 1A). The cut surface of the appendix was fleshy and slightly myxoid (Fig. 1B). On microscopic examination, normal appendiceal tissue was replaced by proliferation of spindle cells in a collagenous and slightly myxoid background with scattered blood vessels (Fig. 1C). Plate-like collagen was seen focally (Fig. 1D), and the lymphoplasmacytic inflammatory infiltrate was relatively sparse. The proliferative spindle cells displayed bland cytology with low mitotic count (about 1/10 high power fields) and no necrosis. The external surface of the appendix was partly accompanied by fibrous adhesions with dense inflammatory cell infiltrates (Fig. 1E). Immunostains on spindle cells were positive for vimentin and smooth muscle actin (Fig. 1F 657
OH et al.
A
B
C
D
E
F
G
H
Fig 1. Gross photograph and microscopic and immunohistochemical findings of the appendix. (A) The appendix is tumorous, enlarged, and dilated at the distal portion with a tadpole appearance, measuring 10 9 594.5 cm. (B) The cut surface is fleshy, myxoid, and tan-gray with a partly mucinous component. (C) Spindle-or stellate-shaped cells are arranged in a fascicular pattern in the collagenous and slightly myxoid background with scattered blood vessels (9100). (D) Plate-like thick collagens are scattered in some areas (9100). (E) The lymphoplasmacytic infiltration is partly dense with serosal involvement (940). (F) Smooth muscle actin is expressed in approximately half of spindled tumor cells (9100). (G) Vimentin shows strong and diffuse cytoplasmic immunoreactivity in spindle tumor cells (9100). (H) MUC4 is negative (940).
and G) and negative for S100 protein, ALK, c-kit, desmin, CD21, CD23, and CD35. These immunostaining results support the myofibroblastic and fibroblastic differentiation of the tumor cells. In addition, MUC4 (Fig. 1H) and FISH for translocation t (7:16) (q34: p11) were performed to exclude the possibility of low-grade fibromyxoid sarcoma (LGFMS) and were negative. Ki-67 proliferation index was low (2%), and p53 immunoexpression was not observed. The patient has been in good health with no evidence of recurrence or metastasis at 1-year follow-up after appendectomy. The present appendiceal tumor was finally diagnosed as inflammatory myofibroblastic tumor rather than LGFMS, low-grade myxofibrosarcoma, or inflammatory pseudotumor-like variant of follicular dendritic cell sarcoma. The diagnosis was based on the previously described histologic fea-
tures, immunohistochemical findings, and molecular studies. The negative ALK immunostaining does not preclude a diagnosis of IMT. In fact, many studies have demonstrated that ALK alterations are detectable in only about 50% of IMTs (1). The etiology of IMT is unclear, but infectious, inflammatory, and immunologic responses have been considered as possible etiologies (11). In rare cases as shown in Table 1, it has been described as associated with trauma (7), neoplasia (8, 9), and previous surgery (10). IMTs in these cases arose 4 months to 9 years after the associated event. In our case, the appendiceal IMT developed 3 years and 5 months after intra-abdominal surgery, and no other possible causes were identified. We speculate that the previous intra-abdominal operation may have contributed to the development of the tumor in this patient. Exposure of the intra-abdom-
Table 1. Previously reported cases of inflammatory myofibroblastic tumor (IMT) after a preceding event Age/sex Etiology Site of IMT Breast parenchyma Case 1 (7) 22/M Trauma (direct blow; fall of a heavy object on the same site of the breast) Case 2 (8) 15/M Neoplasm (Wilms tumor of Upper abdomen involving right kidney) gastroesophageal junction, stomach, and liver Case 3 (9) 3.5/M Neoplasm (Wilms tumor of Liver right kidney) Case 4 (10) 2.5/M Previous surgery (Left Bladder, left inguinal region, herniorrhaphy) and left rectus abdominis muscle
658
Interval duration 4 months 9 years 18 months 28 months
© 2013 APMIS. Published by John Wiley & Sons Ltd
PSEUDOTUMOR OF THE APPENDIX
inal environment to an aggressive gastric cancer or subsequent systemic chemotherapy-associated inflammatory reaction may be other possible contributing factors. To our knowledge, this may be the first case of appendiceal IMT arising after a preceding event.
DISCLOSURE
5.
6.
7.
The authors have no relevant commercial or financial conflicts of interest to declare.
REFERENCES 1. Fletcher CDM, Unni KK, Mertens F, World Health Organization. International Agency for Research on C. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002. 2. Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995;19:859–72. 3. Uludag M, Citgez B, Polat N. Inflammatory pseudotumour of the appendix and acute appendicitis: a case report. Acta Chir Belg 2008;108:451–3. 4. Majumdar K, Sakhuja P, Kaur S, Rastogi A, Gondal R, Agarwal A. Inflammatory myofibroblastic tumor appendix with concomitant mucosal dysplasia, simu-
© 2013 APMIS. Published by John Wiley & Sons Ltd
8.
9.
10.
11.
lating pseudomyxoma on preoperative aspiration cytology. J Cancer Res Ther 2012;8:317–9. Bronzino P, Abbo L, Bagnasco F, Barisone P, Dezzani C, Genovese AM, et al. Intra-abdominal inflammatory myofibroblastic pseudotumor: case report and review of the literature. G Chir 2005;26:362–4. Bonnet JP, Basset T, Dijoux D. Abdominal inflammatory myofibroblastic tumors in children: report of an appendiceal case and review of the literature. J Pediatr Surg 1996;31:1311–4. Vecchio GM, Amico P, Grasso G, Vasquez E, La Greca G, Magro G. Post-traumatic inflammatory pseudotumor of the breast with atypical morphological features: a potential diagnostic pitfall. Report of a case and a critical review of the literature. Pathol Res Pract 2011;207:322–6. Vujanic GM, Milovanovic D, Aleksandrovic S. Aggressive inflammatory pseudotumor of the abdomen 9 years after therapy for Wilms tumor. A complication, coincidence, or association? Cancer 1992;70:2362–6. Newbould MJ, Kelsey A, Lendon M, Gururangan S. Inflammatory pseudotumor of the liver masquerading as a metastasis in a child treated for nephroblastoma. Med Pediatr Oncol 1992;20:172–5. Freud E, Bilik R, Yaniv I, Horev G, Cohen D, Mimouni M, et al. Inflammatory pseudotumor in childhood. A diagnostic and therapeutic dilemma. Arch Surg 1991;126:653–5. Saleem MI, Ben-Hamida MA, Barrett AM, Bunn SK, Huntley L, Wood KM, et al. Lower abdominal inflammatory myofibroblastic tumor -an unusual presentation- a case report and brief literature review. Eur J Pediatr 2007;166:679–83.
659
