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Year : 2023  |  Volume : 66  |  Issue : 2  |  Page : 392-395
STRN-ALK rearranged malignant peritoneal mesothelioma—Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma

1 Department of Pathology, School of Medicine, Koc University, Istanbul, Turkey
2 Department of Gynecology and Obstetrics, School of Medicine, Koc University, Istanbul, Turkey
3 Department of Pathology, School of Medicine, Acibadem University, Istanbul, Turkey

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Date of Submission08-Apr-2021
Date of Decision01-Aug-2021
Date of Acceptance11-Aug-2021
Date of Web Publication26-May-2022


Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.

Keywords: ALK, PAX8, peritoneal malignant mesothelioma, STRN-ALK fusion

How to cite this article:
Bulutay P, Vatansever D, Taskiran C, Mericoz CA, Tokat F, Kapucuoglu N, Kulac I. STRN-ALK rearranged malignant peritoneal mesothelioma—Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma. Indian J Pathol Microbiol 2023;66:392-5

How to cite this URL:
Bulutay P, Vatansever D, Taskiran C, Mericoz CA, Tokat F, Kapucuoglu N, Kulac I. STRN-ALK rearranged malignant peritoneal mesothelioma—Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Jun 3];66:392-5. Available from:

   Introduction Top

Malignant peritoneal mesothelioma (MPM) accounts for 10–30% of all malignant mesothelioma cases and is rarely seen in children and adolescents.[1] The prior asbestos exposure history is found only in 33–50% of MPMs.[2] The pathogenesis remains unclear. In the context of recurrent somatic and/or germline “breast cancer-associated protein 1” (BAP1), mutations have been noted in 50–70% of MPMs.[3] Additionally, anaplastic lymphoma kinase (ALK) gene rearrangement has been recently shown in a small subset of the MPM cases (3.4%).[4] Low-grade serous carcinoma (LGSC) represents approximately 6–8% of all ovarian cancers.[5] Since both are rare at a young age and they have some morphological and immunohistochemical overlapping features, the clinical and morphological distinction of MPMs from serous ovarian neoplasms can be difficult. Here, we present an ALK-rearranged MPM case that clinically, morphologically, and immunohistochemically mimics LGSC.

   Case Presentation Top

An 18-year-old female with no family history of cancer and no previous exposure to asbestos was presented with abdominal pain and swelling. Magnetic resonance imaging revealed bilateral-multiloculated cystic adnexal masses, which consisted of 4-cm solid and 13-cm cystic component in the right ovary and 3-cm solid and 11-cm cystic component left ovary [Figure 1]a. Serum Cancer antigen-125 (CA-125) level was elevated (232 U/ml). In the frozen section, the tumor was exhibiting small papillae, nests, and micropapillary formations, and some psammoma bodies were seen. The intraoperative diagnosis was given as “low-grade serous ovarian carcinoma.” She underwent debulking surgery, consisting of a total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, splenectomy, cholecystectomy, sigmoid colon resection, total peritonectomy, bladder peritoneum stripping, and paraaortic lymph node dissection. A histopathological examination of the resected specimens revealed that the tumor was forming from the numerous papillary, micropapillary structures, and some solid sheets. The tumor cells were round, oval, and polygonal in shape with small nucleoli, and there was a mild-to-moderate nuclear pleomorphism [Figure 1]b, [Figure 1]c. There was extensive bilateral ovarian surface involvement. The posterior face of the uterus was almost completely covered by tumoral implants as well. Dispersedly settled psammoma bodies were also easily seen [Figure 1]d. Three of the 20 dissected paraaortic lymph nodes were also metastatic.
Figure 1: (a) Malignant peritoneal mesothelioma radiological and histopathological features: magnetic resonance image (MRI) of bilateral cystic masses with some papillary projections through the cyst wall. (b) Tumor cells sharing multiple papillary projections radiating from a central fibrovascular core (H and E; ×40). (c) Higher magnification of papillary projections with mild-to-moderate nuclear atypia (H and E; ×200). (d) Psammoma body formations on the right (H and E; ×200)

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With these features, we included LGSC as well as MPM in our differential diagnosis and performed a wide immunohistochemical (IHC) panel using primary monoclonal antibodies against Wilms' Tumor protein-1 (WT1) (Cell Marque, 6F-H2), Paired box gene 8 (PAX 8) (Cell Marque, MRQ50, 1:100), Estrogen Receptor (ER) (Ventana, SP1), Progesterone Receptor (PR) (Ventana, 1E2), p53 (ScyTek, DO7, 1:200), Calretinin (Ventana, SP65), Cytokeratin 5/6 (CK 5/6) (Biocare, CK 5/6), CK 7 (Cell Marque, OV-TL 12/30, prediluted), Claudin4 (Invitrogen, 3E2C1, 1/200), BerEp4 (Biocare, BerEp4), and BRCA1 Associated Protein 1 (BAP1) (Santa Cruz, C-4, 1:50) with a Benchmark XT Automating Staining System (Ventana).

The IHC revealed that the tumor cells were positive for the mesothelial markers as WT1, calretinin, CK 5/6 as well as CK 7, whereas negative for antimesothelial markers as claudin4 and BerEp4. The tumor cells were also diffusely positive with PAX8 and focally positive with ER and PR [Figure 2]. There was wild-type p53 expression in tumor cells. Both these morphologic and IHC features led us to define a diagnosis of “epithelioid type peritoneal malignant mesothelioma.” IHC BAP1 loss was not observed. She received three cycles of adjuvant paclitaxel and carboplatin therapy after cytoreductive surgery. It has been eight months since the operation had and no recurrence has been observed; the patient is still clinically and radiologically disease-free. Since ALK rearrangement has been shown in some rare MPM cases in recent studies, we also evaluated the ALK rearrangements by using different methods together.
Figure 2: Tumoral immunohistochemical staining profile (DAB; ×200). (a) Calretinin diffuse positive. (b) PAX8 diffuse nuclear positive. (c) WT1 diffuse nuclear positive. (d) CK5/6 diffuse positive. (e) CK7 diffuse positive. (f) Claudin 4 negative. (g) BerEb4 negative. (h) ER focal scattered nuclear positive. (i) PR focal scattered nuclear positive

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After the viable tumor sample was deparaffinized for RNA isolation, DNA and RNA were obtained using the Qiagen AllPrep Kit isolation kit. The concentration measurement of the obtained RNA was done with the Qubit HS RNA Assay kit (178.7 ng/μl). The library was prepared for sequencing with the ArcherDx Fusion Plex CTL for Illumina kit. The library was then sequenced with the Illumina NextSeq 500 instrument using the Illumina flow cell. Sequence data were analyzed with Archer Analysis V6.2.7 and evaluated by I. Kulac and C. Mericoz. The genes targeted by the Archerr FusionPLex CTL are as follows: AKT1, ALK, BRAF, CCND1, CTNNB1, DDR2, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, GNAS, HRAS, IDH1, IDH2, KRAS, MAP2K1, MET, NRAS, NRG1, NTRK1, NTRK2, NTRK3, PIK3CA, PPARG, RAF1, RET, ROS1, THADA. After the analysis of sequencing data, a fusion between exon 20 of the ALK gene and exon 3 of the STRN gene was detected.

Fluorescence in-situ hybridization (ZytoLight SPEC ALK Dual Color Break Apart Probe Kit; Zytovision, Bremerhaven, Germany) and IHC (D5F3 antibody; Ventana, AZ, USA) assays were applied. The tumor cells showed strong and diffuse, granular cytoplasmic staining with ALK antibody [Figure 3]a; ALK break-apart was detected in 30% of tumor cells by the Fluorescence in situ hybridization (FISH) technique [Figure 3]b.
Figure 3: (a) Diffuse strong cytoplasmic ALK immunohistochemistry positivity in tumor cells (×200). (b) ALK break-apart FISH utilizes DNA probes that hybridize to the 3′ (red signal) and 5′ (green signal) regions of the common fusion breakpoint in ALK. ALK rearrangement is identified by splitting of the red and green signals in both nuclei in this field

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   Discussion Top

Both MPM and LGSC are rare tumors, and no standard treatment strategy is available owing to their rarity. ALK translocation can be observed in various cancer types, primarily non-small cell lung cancers.[6] Discovery of ALK rearrangements in MPMs raises the possibility of treatment with ALK inhibitors.[7] There is a total of 16 ALK-rearranged MPM cases shown in the literature by molecular methods. Among these, ALK translocated most frequently with STRN (54.8%) and TPM1 (27.2%), ATG16L1 (9%), FN1 (9%), respectively.[4] BAP1 alteration was detected in almost 69% of the MPM cases and also 31% of them have concomitant alterations in PRBRM1 (46%) and SETD2 (35%) with BAP1. However, any of them are associated with ALK translocation so far. The fact that the ALK translocation accompanying BAP1 alteration in MPMs has not been detected in the literature yet may strengthen the possibility of different pathogenetic pathways.

The main differential diagnosis of epithelioid MPM is LGSC because they present over a wide age range in women.[8] LGSC histologically exhibits a variety of patterns, including micropapillae, compact cell nests, elongated papillae, glandular, or macropapillae formations with mild-to-moderate nuclear atypia as MPMs and typically diffusely positive for cytokeratin 7 (CK7), PAX8, ER, and WT.[9]

PAX8 staining in mesotheliomas is so low, however, a recent study has reported the PAX8 expression 22.5% in their MPM cohort.[10] In conclusion, here we present an unusual MPM case showing STRN-ALK translocation in a young female and mimicking LGSC along with diffuse PAX8 expression and overlapping histological features. Although it is rare, epithelioid malignant mesothelioma (MM) should be considered in the differential diagnosis of ovarian and peritoneal tumors of young females. To avoid misdiagnosis, extended IHC markers should be used to differentiate serous carcinomas and epithelioid MPM. Also, we would like to emphasize the importance of molecular testing for MPM, especially in young patients with no history of asbestos exposure situations, because ALK inhibitors could be a treatment option for this small subset of patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Thomas A, Chen Y, Yu T, Gill A, Prasad V. Distinctive clinical characteristics of malignant mesothelioma in young patients. Oncotarget 2015;6:16766-73.  Back to cited text no. 1
Attanoos RL, Churg A, Galateau-Salle F, Gibbs AR, Roggli VL. Malignant mesothelioma and its non-asbestos causes. Arch Pathol Lab Med 2018;142:753-60.  Back to cited text no. 2
Leblay N, Leprêtre F, Le Stang N, Gautier-Stein A, Villeneuve L, Isaac S, et al. BAP1 is altered by copy number loss, mutation, and/or loss of protein expression in more than 70% of malignant peritoneal mesotheliomas. J Thorac Oncol 2017;12:724-33.  Back to cited text no. 3
Hung YP, Dong F, Watkins JC, Nardi V, Bueno R, Dal Cin P, et al. Identification of ALK rearrangements in malignant peritoneal mesothelioma. JAMA Oncol 2018;4:235-8.  Back to cited text no. 4
Gershenson DM, Bodurka DC, Lu KH, Nathan LC, Milojevic L, Wong KK, et al. Impact of age and primary disease site on outcome in women with low-grade serous carcinoma of the ovary or peritoneum: Results of a large single-institution registry of a rare tumor. J Clin Oncol 2015;33:2675-82.  Back to cited text no. 5
Bulutay P, Akyürek N, Memiş L. Clinicopathological and prognostic significance of the EML4-ALK translocation and IGFR1, TTF1, napsin a expression in patients with lung adenocarcinoma. Turk J Pathol 2020;37:7-17.  Back to cited text no. 6
Rüschoff JH, Gradhand E, Kahraman A, Rees H, Ferguson JL, Curioni-Fontecedro A, et al. STRN -ALK rearranged malignant peritoneal mesothelioma with dramatic response following ceritinib treatment. JCO Precis Oncol 2019;3:PO.19.00048.  Back to cited text no. 7
Mani H, Merino MJ. Mesothelial neoplasms presenting as, and mimicking, ovarian cancer. Int J Gynecol Pathol 2010;29:523-8.  Back to cited text no. 8
Ahn G, Folkins AK, McKenney JK, Longacre TA. Low-grade serous carcinoma of the ovary: Clinicopathologic analysis of 52 invasive cases and identification of a possible noninvasive intermediate lesion. Am J Surg Pathol 2016;40:1165-76.  Back to cited text no. 9
Malpica A, Euscher ED, Marques-Piubelli ML, Ferrufino-Schmidt MC, Miranda RN, Sams R, et al. Malignant mesothelioma of the peritoneum in women: A clinicopathologic study of 164 cases. Am J Surg Pathol 2021;45:45-58.  Back to cited text no. 10

Correspondence Address:
Pinar Bulutay
Department of Pathology, Koc University School of Medicine, Zeytinburnu, Istanbul 34010
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_360_21

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