Primary splenic carcinosarcoma with local invasion of chest wall: a rare case

Primary splenic carcinosarcoma with local invasion of chest wall: a rare case 一例脾脏原发性肉瘤侵犯胸壁的病例报道 first-author corresp ‡Corresponding Author ‡Corresponding Author †E-mail:bigzyun1977@zju.edu.cn †E-mail:bigzyun1977@zju.edu.cn bigzyun1977@zju.edu.cn Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China We herein present a case of carcinosarcoma arising as a primary lesion in the spleen with the presence of local invasion of chest wall prior to widespread metastasis all over the body of a female aged 64 years. The detailed information of therapy and imaging evidences of morphology, histology, and immunohistochemistry are fully provided. To the best of our knowledge, this is the fifth reported case of a primary splenic carcinosarcoma and even the first case to be described with local invasion in the mongoloid. Carcinosarcoma that develops in the spleen with local invasion is extremely rare. 本文报道了一例伴有胸壁局部侵犯的脾脏原发性肉瘤的64岁女性病例。在采用正电子发射计算机断层显像（PET/CT）等先进方法对肿瘤及转移灶进行了及时准确的诊断后，患者接受了根治性手术。同时标本经过苏木精-伊红染色法（H&E）和免疫组化等检查进一步明确了脾脏原发性肉瘤的病理学诊断结果。据我们所知，这是目前世界上第五例原发性脾脏肉瘤的报道，同时也是第一例伴有局部胸壁侵犯并获得手术根治的脾脏肉瘤的报道。 Spleen Carcinosarcoma Chest wall invasion 脾脏 肉瘤 胸壁侵犯 Introduction 1 Carcinosarcomas, containing both epithelial and connective tissue components, are rare malignant neoplasms, which commonly arise from the female genital tract (Steeper et al., 1983 1983 ; Gadducci and Romanini, 2001 2001 ; Cicin et al., 2008 2008 ), and sometimes from extragenital sites (Isimbaldi et al., 1996 1996 ; di Vizio et al., 2001 2001 ). Carcinosarcomas originating in the spleen are extraordinarily rare. There have been no more than four reported cases of primary carcinosarcomas of the spleen in English-language literature. Westra et al. ( 1994 1994 ) reported the first case of primary splenic carcinosarcoma, which was thought to arise from the mesothelium, reflecting the unique capacity of the female mesothelium for mullerian differentiation. Rao et al. ( 2007 2007 ) reported a case of splenic carcinosarcoma of a male, which was characterized by the presence of an osteosarcomatous element and raised β human chorionic gonadotropin (β-hCG) levels. Kochar et al. ( 2009 2009 ) presented a Caucasian man with a high-grade malignant pleomorphic tumor with areas of necrosis, and this case revealed osteosarcomatous differentiation and a spindle and epithelioid morphology. Most recently, Joy et al. ( 2012 2012 ) reported another case of primary splenic carcinosarcoma. However, no imaging evidence of morphology, histology, or immunohistochemistry was provided. Herein, we report a case of carcinosarcoma arising as a primary lesion in the spleen of a female aged 64 years. The feature of this tumor is the presence of local invasion of the chest wall prior to wide metastasis all over the body. As far as we are aware, this is the fifth reported case of a primary splenic carcinosarcoma and the first case to be described with the local invasion in the mongoloid. Case presentation 1 The patient is a 64-year-old mongoloid female who was admitted with persistent dull pain of the left middle trunk, limited to the left upper quadrant and left lower anterior chest wall. She denied any other symptoms, except for occasional shortness of breath. She gave a medical history of hypertension. On physical examination, there was tenderness in the left upper quadrant and left lower anterior chest wall. There were no palpable lymph nodes or mass, and chest examination revealed decreased breath sound of the left lung. Blood analysis showed an elevated white cell count (11.4×10 9 cells/L) and mild anaemia. The analysis of tumor markers showed elevated carcinoembryonic antigen (CEA, 12.95 ng/ml), cancer antigen 125 (CA125, 1041.90 U/ml), and CA153 (119.70 U/ml). The other markers including CA199 and alphafetoprotein (AFP), as well as other hematological and biochemical parameters, were normal. Chest radiograph showed a moderate amount of effusion of the left pleural cavity (Fig. 1a 1a ), and percutaneous drainage was performed. Abdominal ultrasound showed a markedly enlarged spleen with a diameter of 22 cm, with a mass of abnormally high echogenicity in the lower splenic pole and areas of low echogenicity within the spleen, but no ascites. Computed tomography (CT) showed a high-density mass in the lower pole of the spleen (Fig. 1b 1b ), accompanied by multiple cystic solid mass in the spleen and a 6.1 cm×3.6 cm mass shadow with the bone destruction of the left anterior fifth rib (Fig. 1c 1c ). The upper gastrointestinal endoscopy, as well as colonoscopy, was also performed without positive findings. The positron emission tomography/computed tomography (PET/CT) scan confirmed multiple low-density mass and one high-density mass distributed in the spleen, and a soft tissue mass shadow with local rib destruction (Figs. 1d and 1e 1d and 1e ). There were no other abnormalities found on the PET/CT. Accordingly, primary splenic malignancy was first considered. Then the persistent severe pain caused by the tumors had brought an intolerable burden on her body and mentality. This patient has no pertinent family history, In consideration of the limited distribution of tumors, the palliative splenectomy in combination with resection of the rib tumor was performed. An open radical resection was performed (Yan et al., 2015 2015 ) and the operation showed an enlarged spleen adhesive to the surrounding chest wall, splenic flexure of colon and diaphragm. The other internal organs were entirely normal. (a) Chest radiograph showed a moderate amount of effusion of the left pleural cavity. (b, c) Computed tomography (CT) showed a high-density mass in the lower pole of the spleen (b), accompanied by multiple cystic solid mass in the spleen and a 6.1 cm×3.6 cm mass shadow with the bone destruction of the left anterior fifth rib (blue arrow) (c). (d, e) The positron emission tomography/computed tomography (PET/CT) scan confirmed multiple low-density mass and one high-density mass distributed in the spleen, and a soft tissue mass shadow with local rib destruction. There were no other abnormalities found on the PET/CT The tissue samples were prepared and embedded in paraffin. The paraffin blocks were sectioned to a thickness of 5 µm and stained with hematoxylin and eosin (H&E). Stained sections were visualized under an optical microscope. The procedures of immunohistochemistry were performed on an automated Ventana BenchMark immunostainer (Roche, Basel, Switzerland) at the Department of Pathology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, China. Postoperatively, the intractable pain was obviously relieved, and even disappeared. One month post operation, follow-up indicated that this patient recovered well without evident recurrence of tumor and could do some housework. The patient was then reviewed by an oncologist who advised treatment with palliative chemotherapy, consisting of cisplatin and etoposide. Results 1 Gross observation 2 The spleen was enlarged, weighing 2980 g and measuring 25 cm×15 cm×15 cm. The external surface was bosselated, and the cut surface revealed an undefined, heterogenous soft mass in the lower pole, measuring up to 9.0 cm×8.0 cm×4.2 cm (Fig. 2a 2a ). The dividing line was not clear all round the mass, and there was no obvious coating observed. The multiple cystic solid mass proved to be hematoncus. (a) Gross section of spleen showing tumor nodule located in the lower pole. (b–e) Histological appearance of splenic carcinosarcoma: (b) shows the coexistence of tumor tissue and normal splenic tissue; (c) shows lots of necrotic tissues in the central region of the tumor; (d) shows the sarcomatous component composed of uniform spindle cells arranged in a fascicular pattern; (e) shows the carcinomatous component composed of irregular granular cells, showing frequent megakaryocytes. (f–g) Histological appearance of the metastatic tumor of the chest wall: (f) shows the tumor tissue invading the striated muscle; (g) shows the tumor tissue encompassing the nerve fiber. (h–j) Splenic carcinosarcoma immunohistochemistry: (h) indicates that sarcomatous areas show strong immunostaining for vimentin; (i) indicates that carcinomatous areas reveal strong positive staining for cytokeratin (CK; pan); (j) shows positive epithelial membrane antigen (EMA) immumohistochemistry The rib mass appeared as a soft grayish-white mass with the size of 4.0 cm×3.0 cm×2.0 cm, and adhered seriously to the surrounding bone and intercostal muscles. Optical microscopy 2 Histological images showed a low-grade malignant tumor of patchy distribution, accompanied by areas of necrosis. The neoplasm without coating invaded the normal tissue of the spleen. There were distinct areas of necrotic tissue. The rest of the tumor showed a spindle and epithelioid morphology on optical microscopy. The spindle tumor cells showed no distinctive atypia and fewer mitoses, while the epithelioid cells varied in size and shape, and had a vague boundary (Figs. 2b–2e 2b–2e ). The neoplasm of chest wall also showed cellular morphologies similar to the splenic malignancy. The tumor tissue, invading the surrounding striated muscle and encompassing the nerve fiber, was also observed (Figs. 2f and 2g 2f and 2g ). There was no evidence of any glandular or squamous differentiation. There were no features of any other sarcoma. The tissue samples resected from splenic flexure of the colon and diaphragm proved histologically to be tissue hyperplasia caused by chronic inflammation. Immunohistochemistry 2 For immunohistochemical analysis, the tumor cells revealed strong immunoreactivity for vimentin (Fig. 2h 2h ). There was patchy but convincing positivity for cytokeratin (CK; pan) and epithelial membrane antigen (EMA) (Figs. 2i and 2j 2i and 2j ). The tumor cells were negative for F8, CD31, CD34, SMA, Desmin, S100, HMB-45, Calretinin, HBME-1, and TTF-1, and focally weakly positive for CD68. To summarize, this was a poorly differentiated malignant tumor with essentially 2 components, i.e. the spindle and epithelioid components. This is consistent with a carcinosarcoma showing heterologous differentiation. Discussion 1 Carcinosarcomas are rare biphasic malignant tumors. Histological analysis of tumors has shown characteristics of epithelial carcinoma and mesenchymal differentiation. They occurred in many anatomical locations such as the female genital tract (Dave et al., 2011 2011 ; Kanthan and Senger, 2011 2011 ), pelvic peritoneum (Ko et al., 2005 2005 ), breast (Cornette et al., 2005 2005 ), stomach (Iezzoni and Mills, 1993 1993 ), colon (Isimbaldi et al., 1996 1996 ), pancreas (Darvishian et al., 2002 2002 ; Chmiel et al., 2005 2005 ), head and neck, respiratory system, hepatobiliary system, thyroid, thymus, and skin. A malignant mass arising within the spleen is most commonly of a lymphoreticular origin (Kochar et al., 2009 2009 ). The finding of carcinosarcoma in the spleen is very rare. In this case, sarcomatous areas consisted of uniform spindle cells, while carcinomatous areas were composed of irregular granular cells with frequent megakaryocytes. The signs and symptoms for primary splenic malignancy lack specificity. Many preoperative and/or postoperative examinations, such as physical examination, abdominal ultrasound, CT scan, and endoscopic examination of the gastrointestinal tract, have to be conducted to exclude the metastatic neoplasms prior to the diagnosis of primary splenic tumor (Kochar et al., 2009 2009 ). In our limited experience, PET/CT could be helpful to the above procedures. In addition, the collision tumor representing synchronous carcinoma and sarcoma from separate sources (Thompson et al., 1996 1996 ), and endometriosis-associated extragenital carcinosarcomas (Booth et al., 2004 2004 ), should also be differentially diagnosed from primary carcinosarcoma of the spleen. The histogenesis and biological behavior of carcinosarcoma are not fully understood. Surface mesothelium has been proposed as the origin of splenic epithelial tumors (Rao et al., 2007 2007 ). Some people stated that such tumors arose from invaginated mesothelium of malignant transformation or a pre-existing embryonic rest (Morinaga et al., 1992 1992 ; Rao et al., 2007 2007 ). We are more inclined to believe that the neoplasm in this case probably arose directly from the spleen, in the absence of evidence to support metastasis from other sites. So far, the survival time of splenic carcinosarcoma patients post operation ranged from 3 to 12 months (Westra et al., 1994 1994 ; Rao et al., 2007 2007 ; Kochar et al., 2009 2009 ; Joy et al., 2012 2012 ). This may be because of the rapid spread and highly invasive nature of these lesions (Rao et al., 2007 2007 ). The metastatic paths of carcinosarcoma could include the bloodstream and lymphatic metastasis, local spread, and so on. In our case, only local metastasis of the chest wall occurred, and resulted in severe pain, which could be related to the early stage of this tumor. Follow-up observation will determine whether other metastasis happened subsequently. To date, there are no guidelines available for the treatment of splenic carcinosarcoma. It is generally agreed that complete macroscopic excision of the malignancy may provide the best chance of survival (Kochar et al., 2009 2009 ). Postoperatively, adjuvant treatments, such as chemotherapy and radiotherapy, should be under consideration to further kill the tumor cells and improve the prognosis of patients. For chemotherapy, both the carcinomatous and the sarcomatous components have to be addressed. There is no consensus concerning optimal chemotherapeutic regimes (Kochar et al., 2009 2009 ). Ifosfamide and cisplatin combination therapy has been reported to offer a better survival rate (Ko et al., 2005 2005 ). Cyclophosphamide-doxorubicin-containing chemotherapy has been suggested for breast carcinosarcoma (Cornette et al., 2005 2005 ). Some researchers stated that carcinosarcomas responded better to cisplatin-based regimes (Gadducci and Romanini, 2001 2001 ). Some other regimens, such as ovarian-type chemotherapeutic regimens combining cisplatin, etoposide, cyclophosphamide, doxorubicin and paclitaxel, sarcoma-type regimens combining doxorubicin, ifosfamide, and dacarbazine, were also reported for carcinosarcomas (Resnik et al., 1995 1995 ; Cass et al., 1996 1996 ; Cicin et al., 2008 2008 ). For splenic carcinosarcoma, Kochar et al. ( 2009 2009 ) applied cisplatin and etoposide combination therapy to treat a 60-year-old Caucasian man, who died 7 months after diagnosis attributed to the wide metastasis. Although various combinations of chemotherapy have been explored, an optimal therapeutic modality is yet to be determined (Kanthan and Senger, 2011 2011 ). Adjuvant radiotherapy has been used to treat carcinosarcoma (Park et al., 2011 2011 ). However, its value in addition to systemic treatment remains ill-defined (Dave et al., 2011 2011 ). Park et al. ( 2011 2011 ) investigated the influence of adjuvant radiotherapy on patterns of failure and survivals in uterine carcinosarcoma, and indicated that adjuvant radiotherapy after surgical resection was effective in decreasing loco-regional recurrence, and most treatment failures were due to distant metastasis. The combined chemo-radiotherapeutic approach has also been adopted and has shown survival benefit for uterine carcinosarcoma patients (Galaal et al., 2009 2009 ). In brief, multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment. Ko et al. ( 2005 2005 ) reported a case of a primary carcinosarcoma of the pelvic peritoneum with five-year disease-free survival after managing the patient with surgery, chemotherapy, and radiotherapy. Evidence gained from the above regimens for carcinosarcomas of different original sites may be beneficial for the treatment of the splenic tumor. It seems unlikely to be able to conduct any trial to test different regimes, because these tumors are so rare. Regardless of the treatment, the prognosis of carcinosarcoma is universally poor. Conclusions 1 Splenic carcinosarcoma is a rare tumor with embryological origin. There have been just four previously reported cases of primary splenic carcinosarcoma. Every effort should be made to carefully exclude other primary sites before reaching the diagnosis of primary carcinosarcoma. There is no consensus regarding the optimal treatment strategy for this disease. Multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment. The prognosis of carcinosarcoma is universally poor. Contributors 2 Yun ZHANG carried out the work of diagnosis and treatment; Ting SUN and Gui-feng WANG wrote and revised the paper. 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Laparoscopic versus open distal pancreatectomy for benign or premalignant pancreatic neoplasms: a two-center comparative study . J Zhejiang Univ-Sci B (Biomed & Biotechnol) , 2015 . 16 ( 7 ): 573 - 579 . DOI: 10.1631/jzus.B1400257 http://doi.org/10.1631/jzus.B1400257 . Laparoscopic versus open distal pancreatectomy for benign or premalignant pancreatic neoplasms: a two-center comparative study Compliance with ethics guidelines Ting SUN, Gui-feng WANG, and Yun ZHANG declare that they have no conflict of interest. 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 was obtained from the patient for being included in the study. 10.1631/jzus.B1700262 Project supported by the National Natural Science Foundation of China (Nos. 81471623, 81270446, and 81130007) 2017-05-17 2017-06-02 2022-01-05 Copyright © Zhejiang University and Springer-Verlag Berlin Heidelberg 2017 2017 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 08 18