Clin J Gastroenterol (2014) 7:228–232 DOI 10.1007/s12328-014-0479-1
CASE REPORT
Clear cell sarcoma of the esophagus: report of a case Daisuke Ishii • Mitsuhiro Inagaki • Tatsuya Shonaka • Hiromitsu Akabane • Naoyuki Yanagida • Hiroki Shomura • Tatsuya Orimo • Takeshi Aiyama • Keisuke Sato • Shiro Nakano
Received: 3 February 2014 / Accepted: 12 March 2014 / Published online: 30 March 2014 Ó Springer Japan 2014
Abstract We report a rare case of clear cell sarcoma of the esophagus and review the literature regarding clear cell sarcomas of the gastrointestinal tract. A 57-year-old male was admitted with dysphagia during swallowing. Preoperative imaging studies, including upper gastrointestinal endoscopy and endoscopic ultrasonography, showed that the tumor was located between the mucosa and the muscularis propria of the lower esophagus. We performed subtotal esophagectomy with gastric tube reconstruction. Pathological findings of the tumor showed mixed spindle cells and oval cells. Immunohistochemical staining showed that the tumor cells were positive for S-100, vimentin and neuron-specific enolase and negative for a-smooth muscle actin, myoglobin and c-kit. Fluorescence in situ hybridization using a Ewing sarcoma breakpoint region 1 probe showed split signals in a small percentage of cells. We finally diagnosed the patient with clear cell sarcoma of the esophagus. Keywords Esophagus Clear cell sarcoma (CCS) Submucosal tumor
D. Ishii (&) M. Inagaki T. Shonaka H. Akabane N. Yanagida H. Shomura T. Orimo T. Aiyama S. Nakano Division of Surgery, Hokkaido P.W.F.A.C Asahikawa-Kosei General Hospital, 1 Jo 24 Chome 111, 1 Jodori, Asahikawa 078-8211, Japan e-mail: [email protected] K. Sato Department of Pathology, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
123
Introduction Clear cell sarcoma (CCS) is a soft tissue neoplasm that is assumed to be derived from neural crest cells and melanocytes [1]. Reported cases of CCS of the gastrointestinal tract are extremely rare [2–22]. There are no previously published reports of CCS of the esophagus. We report a resected case of CCS of the esophagus and review the literature regarding CCSs of the gastrointestinal tract.
Case report A 57-year-old male who had been experiencing dysphagia since December 2011 underwent clinical examinations in April 2012. Upper gastrointestinal endoscopy revealed a tumor of the lower esophagus. His family history was unremarkable. He was a smoker (25 cigarettes a day for 35 years) and regularly consumed alcohol (350 ml beer and 200 ml distilled spirits a day). The levels of tumor markers in the serum were carcinoembryonic antigen of 3.6 ng/ml, carbohydrate antigen 19-9 of 8.3 U/ml, squamous cell carcinoma-related antigen of 0.8 ng/ml, cytokeratin 19 fragment of 0.7 ng/ml and a soluble IL-2 receptor level of 309 U/ml. A complete blood cell count and biochemical examination showed normal levels of all evaluated parameters. Upper gastrointestinal endoscopy showed a submucosal tumor spreading to 36 cm from 32 cm below the incisors, which accounted for approximately one-third of the lumen, and was noted as an elevated lesion covered with normal mucosa (Fig. 1a). Gastrointestinal series showed a smooth elevated lesion measuring approximately 4 cm at the lower esophagus. Endoscopic ultrasonography showed a tumor between the mucosa and the muscularis propria. The boundary was
Clin J Gastroenterol (2014) 7:228–232
229
Fig. 1 Findings of gastrointestinal endoscopy and gastrointestinal ultrasonography. a Gastrointestinal endoscopy showed a submucosal tumor of the esophagus 32–36 cm from the incisors. The arrow shows an elevated lesion with normal mucosa. b Gastrointestinal ultrasonography showed a tumor between the mucosa and muscularis propria. The tumor was a well-circumscribed and mainly hyperechoic lesion. The continuity of the mucosa and mucularis propria was normal
Fig. 2 Findings of contrastenhanced CT and positron emission tomography (PET). a Contrast-enhanced CT showed a poorly enhanced tumor at the lower esophagus (arrow). b PET showed that the tumor had abnormal uptake (arrow) (SUV 6.0)
clear, with some parts showing high brightness while the center exhibited low brightness. The continuity of the mucosa and the mucularis propria was normal (Fig. 1b). Contrast-enhanced computed tomography (CT) showed a tumor a poorly enhanced tumor in the lower esophagus. No invasion of any organs, lymph node metastasis or distal metastasis was found (Fig. 2a). Positron emission tomography showed that the tumor had an abnormal accumulation (standard uptake value [SUV] 6.0) (Fig. 2b). There was no other abnormal accumulation. Therefore, we diagnosed the patient with a submucosal tumor of the esophagus. Although we performed endoscopic ultrasound fineneedle aspiration for a histological diagnosis, we could not obtain any specific findings. Preoperatively, we were unable to define the histological diagnosis beyond that the tumor was a type of sarcoma. We diagnosed the sarcoma to have a high malignant potential because of the high SUV. As a result, we selected the same treatment method as that normally performed for esophageal cancer. We therefore performed a subtotal esophagectomy with gastric tube reconstruction. The tumor was found in the lower esophagus, with no invasion and clear boundaries.
The duration of the operation was 5 h and 48 min and the amount of blood lost was 45 g. The resected specimen showed a well-circumscribed mass with submucosal spread of approximately 30 9 23 9 23 mm in the lower thoracic esophagus, about 50 mm from the oral side of the esophagogastric junction (Fig. 3). Pathological findings of the tumor showed mixed spindle cells and oval cells. Part of the spindle cells formed a bundle structure and an intricate array of cells. Other parts with oval cells were rich in chromatin, but this area was relatively small (Fig. 4a). Immunohistochemical staining showed that the tumor cells were positive for CD34, epithelial membrane antigen, S-100, vimentin, SOX-10 and neuron-specific enolase and negative for desmin, a-smooth muscle actin, myoglobin, thyroid transcription factor 1 and c-kit. Fluorescence in situ hybridization (FISH) using a Ewing sarcoma breakpoint region (EWSR) 1 probe showed split signals in a small percentage of cells (Fig. 4b). There was no metastasis of the resected lymph nodes. Therefore, our case was finally diagnosed with CCS of the esophagus. The patient’s postoperative course was uneventful, and he was discharged on the 22nd postoperative day. At
123
230
Clin J Gastroenterol (2014) 7:228–232
Fig. 3 Resected specimen from the esophagus. a The arrow shows that the tumor was soft and smooth. The mucosal surface was normal. b The cut surface of the specimen is shown. The arrows indicate that the tumor was found in the submucosa. The tumor was well circumscribed from the normal mucosa. The inside of the tumor was uniform
Fig. 4 Pathological findings and results of fluorescence in situ hybridization (FISH). a H&E staining. Spindle cells and oval cells were mixed. Part of the spindle cells formed a bundle structure and an intricate array. Other parts of oval cells were rich in chromatin. b FISH using an EWSR1 probe showed split signals in a small percentage of cells. Yellow signals and closed sets of red and green signals show normal 22q12 regions. Split red signals and green signals show the translocation of the 22q12 region. The arrows show the split signals
14 months after undergoing surgical resection he is still alive without any recurrence.
Discussion CCS of the subcutaneous tissue was first recognized in 1965 by Enzinger [23] in a series of 21 cases as clear cell sarcoma of tendons and aponeuroses. It was a rare sarcoma of soft tissue, which usually occurred in tendons and aponeuroses of adolescents and young adults [24]. It was thought that the tissue origin was a neural crest cell or melanocyte [1]; however, it had not been fully defined at that time. Histologically, oval or spindle-shaped relatively
123
uniform tumor cells were densely arranged in alveolarsolid or flux-like reticulum that was pale or eosinophilic with a clear nucleolus [25]. Immunohistochemical studies revealed that virtually all cases were positive for S-100 protein, and many cases showed positive melanoma-related markers, including human melanin black 45 (HMB45), melan-A/melanoma antigen recognized by T cells-1, melanoma adhesion molecule and microphthalmia-associated transcription factor [26]. This made it difficult to distinguish between CCS and melanoma; however, it was noted that there was a diagnostic difference for CCS, because it was also associated with EWS-activating transcription factor 1 and EWS-cAMP response element binding protein 1 fusion genes caused by a chromosomal translocation of
Clin J Gastroenterol (2014) 7:228–232
231
Table 1 Reported cases of clear cell sarcoma of gastrointestinal Case
Age
Sex
Site
Size
LN metastasis
Liver metastasis
S-100
Genetic finding
References
1
38
M
Duodenum
3
?
–
P
ND
[2]
2
37
M
Ileum
6.5
–
?
P
t(12;22)
[3]
3
74
M
Transverse colon
2 9 392
–
?
P
EWS–ATF1
[4]
4
30
M
Stomach
4
–
–
P
t(12;22)
[5]
5
15
F
Jejunum
5
–
–
P
t(12;22)
[6]
6
21
F
Jejunum
4
?
?
P
ND
[6]
7 8
35 37
F F
Ileum Ileum
3.5 4.5
– –
? –
P P
ND ND
[6] [6]
9
13
M
Stomach
6.7
–
–
P
ND
[6]
10
32
M
Ileum
5
?
–
P
ND
[6]
11
41
M
Jejunum
8.7
–
?
P
t(12;22)
[7]
12
57
M
Jejunum
6.5
–
–
P
EWS
[8]
13
35
M
Ileum
1.8
–
?
P
EWS–ATF1
[9]
14
21
F
Ileum
7
?
–
P
EWS–ATF1
[10]
15
47
F
Pancreas
NM
–
–
P
EWS–ATF1
[11]
16
85
F
Small intestine
NM
–
–
P
EWS–ATF1
[11]
17
16
M
Ileum
5
–
–
P
EWS–ATF1
[12]
18
40
M
Stomach
3
?
–
P
ND
[13]
19
81
F
Ascending colon
NM
–
?
P
EWS–CREB1
[14]
20
42
F
Ileum
NM
–
–
P
EWS–CREB2
[14]
21
42
F
Ileum
3.7
–
?
P
EWS–CREB3
[14]
22
51
F
Ileum
2.8
–
? –
P P
EWS EWS–ATF1
[14] [14]
23
18
F
Small intestine
NM
–
24
46
M
Jejunum
11
–
–
P
EWS–ATF1
[15]
25
62
M
Ileum
4
?
?
P
ND
[15]
26
48
M
Cecum
10.5
?
–
P
ND
[15]
27
60
M
Jejunum
10
?
–
P
ND
[15]
28
20
F
Ileum
3
–
–
P
EWS–ATF1
[16]
29
60
M
Ileum
2.4
?
?
P
EWS
[17]
30
46
M
Jejunum
6
?
?
P
ND
[17]
31
10
F
Stomach
7.8
?
?
P
EWS–ATF1
[18]
32
37
M
Jejunum
8.2
–
–
P
EWS
[19]
33
53
F
Small intestine
5
?
–
P
EWS–ATF1
[20]
34
26
F
NM
–
–
P
EWS–CREB1
[20]
35
66
M
Small and big bowel and peritoneum Ileum
2.5
?
–
P
EWS–CREB1
[20] [21]
36
31
F
Ileum
2.8
?
–
P
EWS
37
69
F
Ileum
5.9 9 4.1
–
–
P
EWS
[22]
38
57
M
Esophagus
3.0 9 2.3
–
–
P
EWS
Our
M male, F female, NM not mentioned, P positive, ND not detective, EWS Ewing sarcoma breakpoint
chromosomes 12 and 22. Our present case was negative for c-kit, HMB45 and CD20 by immunochemical staining, but was positive for an EWSR gene mutation. Therefore, our case was finally diagnosed with CCS of the esophagus. CCS is a high-grade cancer, and is frequently associated with metastasis in the lymph nodes and lungs, as well as local recurrence. There are currently no effective
chemotherapy or radiotherapy regimens established for CCS. The five-year survival rate of CCS was reported to be 52 % [27] and tumors [5 cm in size and the presence of necrosis are adverse prognostic factors [28]. The prevalence rate of CCS was reported to be 1.85 % in malignant soft tissue tumors [1]; however, the prevalence rate of CCS of the gastrointestinal tract has not yet
123
232
been determined. CCS of the gastrointestinal tract is extremely rare, and there are no previous reports of esophageal CCS in the English literature when we searched the PubMed database using keywords such as ‘clear cell sarcoma’ and ‘esophagus’ from 1990-2012 (no similar reports could be identified before 1990). There were only 39 reports published from 1993-2012 when we used the keywords ‘clear cell sarcoma’ and ‘gastrointestinal’ and these are summarized in Table 1. Most cases were of small intestinal origin. There were no significant differences in the incidence between males and females. Many cases were detected as submucosal tumors. Metastasis in resected lymph nodes was found in 14 cases, and metastasis to the liver was found in 13 cases. Our patient did not have metastasis in the lymph nodes or any organs, including the liver. He is still alive at present, 14 months after surgery, without any recurrence. In conclusion, we described the first case report of resected CCS of the esophagus. Disclosures Conflict of Interest: Daisuke Ishii, Mitsuhiro Inagaki, Tatsuya Shonaka, Hiromitsu Akabane, Naoyuki Yanagida, Hiroki Shomura, Tatsuya Orimo, Takeshi Aiyama, Keisuke Sato, and Shiro Nakano declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed Consent: Informed consent was obtained from all patients for being included in the study.
References 1. Ohshika S, Yanagisawa M, Itabashi T, et al. A case of clear cell sarcoma of subcutaneous tissue of forearm. Tohokuseisaishi. 2009;50:163–6. 2. Ekfors TO, Kujari H, Isomaki M. Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) in the duodenum: the first visceral case. Histopathology. 1993; 22:255–9. 3. Donner LR, Trompler RA, Dobin S. Clear cell sarcoma of the ileum: the crucial role of cytogenetics for the diagnosis. Am J Surg Pathol. 1998;22:121–4. 4. Fukuda T, Kakihara T, Baba K, et al. Clear cell sarcoma arising in the transverse colon. Pathol Int. 2000;50:412–6. 5. Pauwels P, Debiec-Rychter M, Sciot R, et al. Clear cell sarcoma of the stomach. Histopathology. 2002;41:526–94. 6. Zambrano E, Reyes-Mugica M, Franchi A, et al. An osteoclastrich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: reports of 6 cases of a GIST simulator. Int J Surg Pathol. 2003;11:75–81. 7. Friedrichs N, Testi MA, Moiraghi L, et al. Clear cell sarcoma-like tumor with osteoclast-like giant cells in the small bowel: further evidence for a new tumor entity. Int J Surg Pathol. 2005;13:313–8.
123
Clin J Gastroenterol (2014) 7:228–232 8. Achten R, Debiec-Rychter M, De Wever I, et al. An unusual case of clear cell sarcoma arising in the jejunum highlights the diagnostic value of molecular genetic techniques in establishing a correct diagnosis. Histopathology. 2005;46:472–4. 9. Taminelli L, Zaman K, Gengler C, et al. Primary clear cell sarcoma of the ileum: an uncommon and misleading site. Virchows Arch. 2005;447:772–7. 10. Venkataraman G, Quinn AM, Williams J. Clear cell sarcoma of the small bowel: a potential pitfall. Case report. APMIS. 2005;113:716–9. 11. Covinsky M, Gong S, Rajaram V, et al. EWS–ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Hum Pathol. 2005;36:74–81. 12. Granville L, Hicks J, Popek E, et al. Visceral clear cell sarcoma of soft tissue with confirmation by EWS–ATF1 fusion detection. Ultrastruct Pathol. 2006;30:111–8. 13. Huang W, Zhang X, Li D, et al. Osteoclast-rich tumor of the gastrointestinal tract with features resembling those of clear cell sarcoma of soft parts. Virchows Arch. 2006;448:200–3. 14. Antonescu CR, Nafa K, Segal NH, et al. EWS–CREB1: a recurrent variant fusion in clear cell sarcoma-association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006;12:5356–62. 15. Lyle PL, Amato CM, Fitzpatrick JE, et al. Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma. Am J Surg. 2008;32:858–66. 16. Terazawa K, Otsuka H, Morita N, et al. Clear-cell sarcoma of the small intestine detected by FDG-PET/CT during comprehensive examination of an inflammatory reaction. J Med Invest. 2009;56:70–5. 17. Joo M, Chang SH, Kim H, et al. Primary gastrointestinal clear cell sarcoma: report of 2 cases, one case associated with IgG4related sclerosing disease, and review of literature. Ann Diagn Pathol. 2009;13:30–5. 18. Legmay JP, Ranalli M, Arcila M, et al. Clear cell sarcoma of the stomach. Pediatr Blood Cancer. 2009;53:214–6. 19. Abdulkader I, Cameselle-Teijeiro J, de Alava E, et al. Intestinal clear cell sarcoma with melanocytic differentiation and EWS [corrected] rearrangement: report of a case. Int J Surg Pathol. 2008;16:189–93. 20. Shenjere P, Salman WD, Singh M, et al. Intra-abdominal clearcell sarcoma: a report of 3 cases, including 1 case with unusual morphological features, and review of the literature. Int J Surg Pathol. 2012;20:378–85. 21. Comin CE, Novelli L, Tornaboni D, et al. Clear cell sarcoma of the ileum: report of a case and review of literature. Virchows Arch. 2007;451:839–45. 22. D’Amico FE, Ruffolo C, Romeo S, et al. Clear cell sarcoma of the ileum: report of a case and review of the literature. Int J Surg Pathol. 2012;20:401–6. 23. Enzinger FM. Clear-cell sarcoma of tendons and aponeuroses: an analysis of 21 cases. Cancer. 1965;18:1163–74. 24. Ishida T, Seta A, Horiuchi H, et al. A case of clear cell sarcoma of the first toe. Jpn Soc Clin Cytol. 1991;30:1147–50. 25. Motoi T. The chimera gene of clear cell sarcoma. Byouri to Rinsyo. 2003;21:584–92. 26. Hisaoka M, Ishida T, Kuo TT, et al. Clear cell sarcoma of soft issue. A clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol. 2008;32:452–60. 27. Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med. 2007;131:152–6. 28. Sara AS, Evans HL, Benjamin RS. Malignant melanoma of soft parts (clear cell sarcoma). A study of 17 cases, with emphasis on prognostic factors. Cancer. 1990;65:367–74.
CASE REPORT
Clear cell sarcoma of the esophagus: report of a case Daisuke Ishii • Mitsuhiro Inagaki • Tatsuya Shonaka • Hiromitsu Akabane • Naoyuki Yanagida • Hiroki Shomura • Tatsuya Orimo • Takeshi Aiyama • Keisuke Sato • Shiro Nakano
Received: 3 February 2014 / Accepted: 12 March 2014 / Published online: 30 March 2014 Ó Springer Japan 2014
Abstract We report a rare case of clear cell sarcoma of the esophagus and review the literature regarding clear cell sarcomas of the gastrointestinal tract. A 57-year-old male was admitted with dysphagia during swallowing. Preoperative imaging studies, including upper gastrointestinal endoscopy and endoscopic ultrasonography, showed that the tumor was located between the mucosa and the muscularis propria of the lower esophagus. We performed subtotal esophagectomy with gastric tube reconstruction. Pathological findings of the tumor showed mixed spindle cells and oval cells. Immunohistochemical staining showed that the tumor cells were positive for S-100, vimentin and neuron-specific enolase and negative for a-smooth muscle actin, myoglobin and c-kit. Fluorescence in situ hybridization using a Ewing sarcoma breakpoint region 1 probe showed split signals in a small percentage of cells. We finally diagnosed the patient with clear cell sarcoma of the esophagus. Keywords Esophagus Clear cell sarcoma (CCS) Submucosal tumor
D. Ishii (&) M. Inagaki T. Shonaka H. Akabane N. Yanagida H. Shomura T. Orimo T. Aiyama S. Nakano Division of Surgery, Hokkaido P.W.F.A.C Asahikawa-Kosei General Hospital, 1 Jo 24 Chome 111, 1 Jodori, Asahikawa 078-8211, Japan e-mail: [email protected] K. Sato Department of Pathology, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan
123
Introduction Clear cell sarcoma (CCS) is a soft tissue neoplasm that is assumed to be derived from neural crest cells and melanocytes [1]. Reported cases of CCS of the gastrointestinal tract are extremely rare [2–22]. There are no previously published reports of CCS of the esophagus. We report a resected case of CCS of the esophagus and review the literature regarding CCSs of the gastrointestinal tract.
Case report A 57-year-old male who had been experiencing dysphagia since December 2011 underwent clinical examinations in April 2012. Upper gastrointestinal endoscopy revealed a tumor of the lower esophagus. His family history was unremarkable. He was a smoker (25 cigarettes a day for 35 years) and regularly consumed alcohol (350 ml beer and 200 ml distilled spirits a day). The levels of tumor markers in the serum were carcinoembryonic antigen of 3.6 ng/ml, carbohydrate antigen 19-9 of 8.3 U/ml, squamous cell carcinoma-related antigen of 0.8 ng/ml, cytokeratin 19 fragment of 0.7 ng/ml and a soluble IL-2 receptor level of 309 U/ml. A complete blood cell count and biochemical examination showed normal levels of all evaluated parameters. Upper gastrointestinal endoscopy showed a submucosal tumor spreading to 36 cm from 32 cm below the incisors, which accounted for approximately one-third of the lumen, and was noted as an elevated lesion covered with normal mucosa (Fig. 1a). Gastrointestinal series showed a smooth elevated lesion measuring approximately 4 cm at the lower esophagus. Endoscopic ultrasonography showed a tumor between the mucosa and the muscularis propria. The boundary was
Clin J Gastroenterol (2014) 7:228–232
229
Fig. 1 Findings of gastrointestinal endoscopy and gastrointestinal ultrasonography. a Gastrointestinal endoscopy showed a submucosal tumor of the esophagus 32–36 cm from the incisors. The arrow shows an elevated lesion with normal mucosa. b Gastrointestinal ultrasonography showed a tumor between the mucosa and muscularis propria. The tumor was a well-circumscribed and mainly hyperechoic lesion. The continuity of the mucosa and mucularis propria was normal
Fig. 2 Findings of contrastenhanced CT and positron emission tomography (PET). a Contrast-enhanced CT showed a poorly enhanced tumor at the lower esophagus (arrow). b PET showed that the tumor had abnormal uptake (arrow) (SUV 6.0)
clear, with some parts showing high brightness while the center exhibited low brightness. The continuity of the mucosa and the mucularis propria was normal (Fig. 1b). Contrast-enhanced computed tomography (CT) showed a tumor a poorly enhanced tumor in the lower esophagus. No invasion of any organs, lymph node metastasis or distal metastasis was found (Fig. 2a). Positron emission tomography showed that the tumor had an abnormal accumulation (standard uptake value [SUV] 6.0) (Fig. 2b). There was no other abnormal accumulation. Therefore, we diagnosed the patient with a submucosal tumor of the esophagus. Although we performed endoscopic ultrasound fineneedle aspiration for a histological diagnosis, we could not obtain any specific findings. Preoperatively, we were unable to define the histological diagnosis beyond that the tumor was a type of sarcoma. We diagnosed the sarcoma to have a high malignant potential because of the high SUV. As a result, we selected the same treatment method as that normally performed for esophageal cancer. We therefore performed a subtotal esophagectomy with gastric tube reconstruction. The tumor was found in the lower esophagus, with no invasion and clear boundaries.
The duration of the operation was 5 h and 48 min and the amount of blood lost was 45 g. The resected specimen showed a well-circumscribed mass with submucosal spread of approximately 30 9 23 9 23 mm in the lower thoracic esophagus, about 50 mm from the oral side of the esophagogastric junction (Fig. 3). Pathological findings of the tumor showed mixed spindle cells and oval cells. Part of the spindle cells formed a bundle structure and an intricate array of cells. Other parts with oval cells were rich in chromatin, but this area was relatively small (Fig. 4a). Immunohistochemical staining showed that the tumor cells were positive for CD34, epithelial membrane antigen, S-100, vimentin, SOX-10 and neuron-specific enolase and negative for desmin, a-smooth muscle actin, myoglobin, thyroid transcription factor 1 and c-kit. Fluorescence in situ hybridization (FISH) using a Ewing sarcoma breakpoint region (EWSR) 1 probe showed split signals in a small percentage of cells (Fig. 4b). There was no metastasis of the resected lymph nodes. Therefore, our case was finally diagnosed with CCS of the esophagus. The patient’s postoperative course was uneventful, and he was discharged on the 22nd postoperative day. At
123
230
Clin J Gastroenterol (2014) 7:228–232
Fig. 3 Resected specimen from the esophagus. a The arrow shows that the tumor was soft and smooth. The mucosal surface was normal. b The cut surface of the specimen is shown. The arrows indicate that the tumor was found in the submucosa. The tumor was well circumscribed from the normal mucosa. The inside of the tumor was uniform
Fig. 4 Pathological findings and results of fluorescence in situ hybridization (FISH). a H&E staining. Spindle cells and oval cells were mixed. Part of the spindle cells formed a bundle structure and an intricate array. Other parts of oval cells were rich in chromatin. b FISH using an EWSR1 probe showed split signals in a small percentage of cells. Yellow signals and closed sets of red and green signals show normal 22q12 regions. Split red signals and green signals show the translocation of the 22q12 region. The arrows show the split signals
14 months after undergoing surgical resection he is still alive without any recurrence.
Discussion CCS of the subcutaneous tissue was first recognized in 1965 by Enzinger [23] in a series of 21 cases as clear cell sarcoma of tendons and aponeuroses. It was a rare sarcoma of soft tissue, which usually occurred in tendons and aponeuroses of adolescents and young adults [24]. It was thought that the tissue origin was a neural crest cell or melanocyte [1]; however, it had not been fully defined at that time. Histologically, oval or spindle-shaped relatively
123
uniform tumor cells were densely arranged in alveolarsolid or flux-like reticulum that was pale or eosinophilic with a clear nucleolus [25]. Immunohistochemical studies revealed that virtually all cases were positive for S-100 protein, and many cases showed positive melanoma-related markers, including human melanin black 45 (HMB45), melan-A/melanoma antigen recognized by T cells-1, melanoma adhesion molecule and microphthalmia-associated transcription factor [26]. This made it difficult to distinguish between CCS and melanoma; however, it was noted that there was a diagnostic difference for CCS, because it was also associated with EWS-activating transcription factor 1 and EWS-cAMP response element binding protein 1 fusion genes caused by a chromosomal translocation of
Clin J Gastroenterol (2014) 7:228–232
231
Table 1 Reported cases of clear cell sarcoma of gastrointestinal Case
Age
Sex
Site
Size
LN metastasis
Liver metastasis
S-100
Genetic finding
References
1
38
M
Duodenum
3
?
–
P
ND
[2]
2
37
M
Ileum
6.5
–
?
P
t(12;22)
[3]
3
74
M
Transverse colon
2 9 392
–
?
P
EWS–ATF1
[4]
4
30
M
Stomach
4
–
–
P
t(12;22)
[5]
5
15
F
Jejunum
5
–
–
P
t(12;22)
[6]
6
21
F
Jejunum
4
?
?
P
ND
[6]
7 8
35 37
F F
Ileum Ileum
3.5 4.5
– –
? –
P P
ND ND
[6] [6]
9
13
M
Stomach
6.7
–
–
P
ND
[6]
10
32
M
Ileum
5
?
–
P
ND
[6]
11
41
M
Jejunum
8.7
–
?
P
t(12;22)
[7]
12
57
M
Jejunum
6.5
–
–
P
EWS
[8]
13
35
M
Ileum
1.8
–
?
P
EWS–ATF1
[9]
14
21
F
Ileum
7
?
–
P
EWS–ATF1
[10]
15
47
F
Pancreas
NM
–
–
P
EWS–ATF1
[11]
16
85
F
Small intestine
NM
–
–
P
EWS–ATF1
[11]
17
16
M
Ileum
5
–
–
P
EWS–ATF1
[12]
18
40
M
Stomach
3
?
–
P
ND
[13]
19
81
F
Ascending colon
NM
–
?
P
EWS–CREB1
[14]
20
42
F
Ileum
NM
–
–
P
EWS–CREB2
[14]
21
42
F
Ileum
3.7
–
?
P
EWS–CREB3
[14]
22
51
F
Ileum
2.8
–
? –
P P
EWS EWS–ATF1
[14] [14]
23
18
F
Small intestine
NM
–
24
46
M
Jejunum
11
–
–
P
EWS–ATF1
[15]
25
62
M
Ileum
4
?
?
P
ND
[15]
26
48
M
Cecum
10.5
?
–
P
ND
[15]
27
60
M
Jejunum
10
?
–
P
ND
[15]
28
20
F
Ileum
3
–
–
P
EWS–ATF1
[16]
29
60
M
Ileum
2.4
?
?
P
EWS
[17]
30
46
M
Jejunum
6
?
?
P
ND
[17]
31
10
F
Stomach
7.8
?
?
P
EWS–ATF1
[18]
32
37
M
Jejunum
8.2
–
–
P
EWS
[19]
33
53
F
Small intestine
5
?
–
P
EWS–ATF1
[20]
34
26
F
NM
–
–
P
EWS–CREB1
[20]
35
66
M
Small and big bowel and peritoneum Ileum
2.5
?
–
P
EWS–CREB1
[20] [21]
36
31
F
Ileum
2.8
?
–
P
EWS
37
69
F
Ileum
5.9 9 4.1
–
–
P
EWS
[22]
38
57
M
Esophagus
3.0 9 2.3
–
–
P
EWS
Our
M male, F female, NM not mentioned, P positive, ND not detective, EWS Ewing sarcoma breakpoint
chromosomes 12 and 22. Our present case was negative for c-kit, HMB45 and CD20 by immunochemical staining, but was positive for an EWSR gene mutation. Therefore, our case was finally diagnosed with CCS of the esophagus. CCS is a high-grade cancer, and is frequently associated with metastasis in the lymph nodes and lungs, as well as local recurrence. There are currently no effective
chemotherapy or radiotherapy regimens established for CCS. The five-year survival rate of CCS was reported to be 52 % [27] and tumors [5 cm in size and the presence of necrosis are adverse prognostic factors [28]. The prevalence rate of CCS was reported to be 1.85 % in malignant soft tissue tumors [1]; however, the prevalence rate of CCS of the gastrointestinal tract has not yet
123
232
been determined. CCS of the gastrointestinal tract is extremely rare, and there are no previous reports of esophageal CCS in the English literature when we searched the PubMed database using keywords such as ‘clear cell sarcoma’ and ‘esophagus’ from 1990-2012 (no similar reports could be identified before 1990). There were only 39 reports published from 1993-2012 when we used the keywords ‘clear cell sarcoma’ and ‘gastrointestinal’ and these are summarized in Table 1. Most cases were of small intestinal origin. There were no significant differences in the incidence between males and females. Many cases were detected as submucosal tumors. Metastasis in resected lymph nodes was found in 14 cases, and metastasis to the liver was found in 13 cases. Our patient did not have metastasis in the lymph nodes or any organs, including the liver. He is still alive at present, 14 months after surgery, without any recurrence. In conclusion, we described the first case report of resected CCS of the esophagus. Disclosures Conflict of Interest: Daisuke Ishii, Mitsuhiro Inagaki, Tatsuya Shonaka, Hiromitsu Akabane, Naoyuki Yanagida, Hiroki Shomura, Tatsuya Orimo, Takeshi Aiyama, Keisuke Sato, and Shiro Nakano declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed Consent: Informed consent was obtained from all patients for being included in the study.
References 1. Ohshika S, Yanagisawa M, Itabashi T, et al. A case of clear cell sarcoma of subcutaneous tissue of forearm. Tohokuseisaishi. 2009;50:163–6. 2. Ekfors TO, Kujari H, Isomaki M. Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) in the duodenum: the first visceral case. Histopathology. 1993; 22:255–9. 3. Donner LR, Trompler RA, Dobin S. Clear cell sarcoma of the ileum: the crucial role of cytogenetics for the diagnosis. Am J Surg Pathol. 1998;22:121–4. 4. Fukuda T, Kakihara T, Baba K, et al. Clear cell sarcoma arising in the transverse colon. Pathol Int. 2000;50:412–6. 5. Pauwels P, Debiec-Rychter M, Sciot R, et al. Clear cell sarcoma of the stomach. Histopathology. 2002;41:526–94. 6. Zambrano E, Reyes-Mugica M, Franchi A, et al. An osteoclastrich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: reports of 6 cases of a GIST simulator. Int J Surg Pathol. 2003;11:75–81. 7. Friedrichs N, Testi MA, Moiraghi L, et al. Clear cell sarcoma-like tumor with osteoclast-like giant cells in the small bowel: further evidence for a new tumor entity. Int J Surg Pathol. 2005;13:313–8.
123
Clin J Gastroenterol (2014) 7:228–232 8. Achten R, Debiec-Rychter M, De Wever I, et al. An unusual case of clear cell sarcoma arising in the jejunum highlights the diagnostic value of molecular genetic techniques in establishing a correct diagnosis. Histopathology. 2005;46:472–4. 9. Taminelli L, Zaman K, Gengler C, et al. Primary clear cell sarcoma of the ileum: an uncommon and misleading site. Virchows Arch. 2005;447:772–7. 10. Venkataraman G, Quinn AM, Williams J. Clear cell sarcoma of the small bowel: a potential pitfall. Case report. APMIS. 2005;113:716–9. 11. Covinsky M, Gong S, Rajaram V, et al. EWS–ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Hum Pathol. 2005;36:74–81. 12. Granville L, Hicks J, Popek E, et al. Visceral clear cell sarcoma of soft tissue with confirmation by EWS–ATF1 fusion detection. Ultrastruct Pathol. 2006;30:111–8. 13. Huang W, Zhang X, Li D, et al. Osteoclast-rich tumor of the gastrointestinal tract with features resembling those of clear cell sarcoma of soft parts. Virchows Arch. 2006;448:200–3. 14. Antonescu CR, Nafa K, Segal NH, et al. EWS–CREB1: a recurrent variant fusion in clear cell sarcoma-association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006;12:5356–62. 15. Lyle PL, Amato CM, Fitzpatrick JE, et al. Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma. Am J Surg. 2008;32:858–66. 16. Terazawa K, Otsuka H, Morita N, et al. Clear-cell sarcoma of the small intestine detected by FDG-PET/CT during comprehensive examination of an inflammatory reaction. J Med Invest. 2009;56:70–5. 17. Joo M, Chang SH, Kim H, et al. Primary gastrointestinal clear cell sarcoma: report of 2 cases, one case associated with IgG4related sclerosing disease, and review of literature. Ann Diagn Pathol. 2009;13:30–5. 18. Legmay JP, Ranalli M, Arcila M, et al. Clear cell sarcoma of the stomach. Pediatr Blood Cancer. 2009;53:214–6. 19. Abdulkader I, Cameselle-Teijeiro J, de Alava E, et al. Intestinal clear cell sarcoma with melanocytic differentiation and EWS [corrected] rearrangement: report of a case. Int J Surg Pathol. 2008;16:189–93. 20. Shenjere P, Salman WD, Singh M, et al. Intra-abdominal clearcell sarcoma: a report of 3 cases, including 1 case with unusual morphological features, and review of the literature. Int J Surg Pathol. 2012;20:378–85. 21. Comin CE, Novelli L, Tornaboni D, et al. Clear cell sarcoma of the ileum: report of a case and review of literature. Virchows Arch. 2007;451:839–45. 22. D’Amico FE, Ruffolo C, Romeo S, et al. Clear cell sarcoma of the ileum: report of a case and review of the literature. Int J Surg Pathol. 2012;20:401–6. 23. Enzinger FM. Clear-cell sarcoma of tendons and aponeuroses: an analysis of 21 cases. Cancer. 1965;18:1163–74. 24. Ishida T, Seta A, Horiuchi H, et al. A case of clear cell sarcoma of the first toe. Jpn Soc Clin Cytol. 1991;30:1147–50. 25. Motoi T. The chimera gene of clear cell sarcoma. Byouri to Rinsyo. 2003;21:584–92. 26. Hisaoka M, Ishida T, Kuo TT, et al. Clear cell sarcoma of soft issue. A clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol. 2008;32:452–60. 27. Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med. 2007;131:152–6. 28. Sara AS, Evans HL, Benjamin RS. Malignant melanoma of soft parts (clear cell sarcoma). A study of 17 cases, with emphasis on prognostic factors. Cancer. 1990;65:367–74.
