POST-TRANSPLANT EPITHELIOID INFLAMMATORY MYOFIBROBLASTIC SARCOMA: A CASE REPORT

- Dr. Ritu Garg, Dr. Sumaid Kaul, Dr. Deepshikha Arora, Dr. Vikas Kashyap. Apollo Hospital, New Delhi.

Introduction:Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate biological potential which might recur or rarely metastasize. They usually present as solitary or rarely as multiple mass lesions in abdominopelvic region, lung, mediastinum

1and retroperitoneum of children and young adults . IMT's post hematopoietic stem cell transplantation (HSCT) has been reported in only eight patients till

2date . In postsolid organ transplant, their incidence iseven rarer with only few case reports to support the

3,4evidence .In 2011, Mariño-Enríquez et al.described a novel va r i an t o f IMT, Ep i the l io id Inflammato ry Myofibroblast ic Sarcoma (EIMS). They are characterized by an epithelioidmorphology and prominent neutrophilic inflammatory infiltrate. Clinically, it has a more aggressive behavior with short disease-free survival. Approximately 50% of IMTs aberrantly express ALK protein triggered by clonal rearrangements of ALK gene located on chromosome

52p23 Only 20 cases of EIMS have been reported thus far but none in a post transplant setting. To the best of our knowledge, we are reporting the 1st case of inflammatory myofibroblastic tumor possibly of epitheloid sarcomatous type in a liver transplanted child.

Case report:An18 month old female received a liver transplant in October, 2015 for decompensated chronic liver disease with clinical and biochemical features consistent with “progressive familial intrahepatic cholestasis”. Her post operative period remained uneventful and was discharged in stable condition. No intra abdominalmass lesions were detected on radiology before and soon after the transplant. In May, 2016, she presented with feverand distended abdomen. CT abdomen and PET scan showed FDG avid multiple lesions in omentum, subdiaphragmaticarea andattatched to the serosa of small bowel (figure 1). Their trucut biopsies revealed a mesenchymal neoplasm, positive for vimentin and SMA. All other lineage markers such as caldesmon, C-kit, CD 34, S100, and CD 31 were negative. Since the MIB-1 index was 15-20%, the suspicion of malignancy was high. More representative sample was required for final tumor typing. The patient was operated upon, with a plan to resect all the tumors. Frozen sectionconfirmed the mesenchymal neoplasm.Two large masses measuring 16 and 8cm in their maximum dimensions and 2 smaller nodules (0.5cm, 1cm) attached to the bowel were excised. Their external surface was uniform smooth, grey white. Cut section was vaguely lobulated, grey white and myxoid.Tumor masses from omentum and small bowel showed large areas of necrosis & heamorrhage. See figure.2 for Histomorphology. .

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Figure 1

Discussion:De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common causes of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in

8an age- and sex-matched population . Skin cancers, lymphomas and Kaposi sarcomas occur most frequently after organ transplantation .The incidence of malignancies is increased as a consequence of chronic immunosuppression after solid organ transplantation. E B V i s i m p l i c a t e d i n P o s t T r a n s p l a n t Lymphoproliferative Disorders and Myogenic

8t u m o r s . I M T w i t h p r o m i n e n t e p i t h e l i o i d cytomorphology is very rare. In a study with 73 cases of IMT, Cook et al. found 4 cases that exhibited round cell transformation characterized by large polygonal cells with large nuclei and prominent nucleoli, in a loose,

9pale staining background . One of these 4 cases showed distinctive nuclearmembrane staining pattern of ALK. In 2010, Butrynski et al. reported sustained partial response to the ALK inhibitor crizotinibin a patient with A L K - t r a n s l o c a t e d I M T w i t h e p i t h e l i o i d

1 0cytomorphology . Only 20 cases have been documented in English literature, the clinical, morphological and immunohistochemiocal features of which are summarized in Table below. All of these showed positive signal for ALK translocation resulting from RANBP2-ALK fusion. Accordingly, we infer that RANPB2-ALK fusion gene might be a potential molecular mechanism for the rapid growth and recurrence of EIMS.

Clinical features Morphology Immunohistochemistry Prognosis

Age incidence

Median age

Sex ratio

Location Size

72% adults

5–26 cm

84% intra

abdominal

5:134

Loosely arrayed round to epitheloid neoplastic ce l l s wi th prominent la rge nucleol i &amphophillic to eosinophillic cytoplasm in myxoid background showing neutrophillic infiltrate

SMA Desmin CK ALK CD30 Mean survival : 15.4 months

61%80% (perinuclear)

15.8%96.4%47.4%

1. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. World HealthOrganization Classification of Tumors of Soft Tissue and Bone. 4th ed. Lyon, France: IARC Press; 2013. p. 83–4.2. AsliTufan, GulistanBahat Inflammatory pseudotumors after stem cell transplantation [Hematology Reports 2015; 7:58483. MerihTepeoğlu et al/ Synchronous PosttransplantLymphoproliferative Disorder and Inflammatory Myofibroblastic Tumor of the Lung in a 2-Year-Old Liver Transplanted Boy: A Case ReportExperimental and Clinical Transplantation (2015) 1: 92-954. Hammas N, Chbani L, Rami M, et al. A rare tumor of the lung: inflammatory myofibroblastic tumor. DiagnPathol. 2012;7:83. doi: 10.1186/1746-1596-7-83.5. Mariño-Enríquez A, Wang WL, Roy A, Lopez-Terrada D, Lazar AJ, Fletcher CD, et al. Epithelioid inflammatory myofibroblasticsarcoma:An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J SurgPathol. 2011;35:135–44.6. Horiuchi R, Uchida T, Kojima T, Shikata T. Inflammatory pseudotumor of the liver. Clinicopathologic study and review of the literature.7. Oz Puyan F, Bilgi S, Unlu E, et al. Inflammatory pseudotumor of thespleen with EBV positivity: report of a case. Eur J Haematol. 2004;72(4):285-291.8. PatriziaBurra, Kryssia I Rodriguez-Castro.Neoplastic disease after liver transplantation: focus on de novo neoplasms. World J Gastroenterol2015 August 7; 21(29): 8753-87689. Cook JR, Dehner LP, Collins MH, Ma Z, Morris SW, Coffin CM, et al. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J SurgPathol. 2001;25:1364–71.10. Patel AS, Murphy KM, Hawkins AL, Cohen JS, Long PP, Perlman EJ, et al. RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors. Cancer Genet Cytogenet. 2007;176:107–14.

A primary IHC panel for spindle cell tumor (comprising of SMA, Desmin, Caldesmon, CD 34, C-kit, DOG-1 and S100) was evaluated. Differential diagnoses ofmyxofibroblastic sarcoma, low grade fibromyxoid sarcoma and Inflammatory myofibroblastic tumor were considered. In view of overall morphology and immunoprofile (figure),diagnosis of inflammatory myofibroblastic sarcoma, possibly of epi theloid type was es tabl ished. Literature demonstrated EbsteinBar Virus (EBV) association in post transplant

6-8settings. However, our case did not show immunopositivity with EBV.

VimentinVimentinVimentin SMASMASMA DesmenDesmenDesmen

MIB-1MIB-1MIB-1 ALK-1ALK-1ALK-1

Figure 3

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Figure 2

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Plump epitheloid to spindle shaped cells with indistinct pale, eosinophillic cytoplasm. Pleomorphic nuclei show vesicular chromatin and distinct nucleoli. Rich network of thin walled delicate capillaries with lymphoplasmacytic infiltrate and few neutrophills. Mitotic figures are rare.