Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma characterized by a malignant serous effusion involving body cavities. It usually associated with human herpes virus-8 (HHV-8) and coexpression of Epstein-Barr virus and mostly affects patients with HIV. We report a rare case of cutaneous PEL with an unusual intravascular presentation, combined with Kaposi sarcoma involving the skin, lung, and gastrointestinal tract. The molecular genetic analysis of the sarcoma and lymphoma components, using next-generation sequencing was performed. The patient was a 67-year-old man who presented with multiple cutaneous tumors and mass in the left lung. He died 17 hours after the admission to the hospital. At autopsy, in addition to the cutaneous lesions, tumors in the left lung and gastrointestinal mucosa were detected, and no effusions in the body cavities were seen. The biopsy from the cutaneous lesions, pulmonary, and intestinal tumors revealed histological and immunohistochemical features of Kaposi sarcoma. In addition, the skin biopsy specimens contained a diffuse infiltrate composed of large pleomorphic cells, with focal intravascular growth that were negative for pan B-cell markers, weakly positive for CD38 and CD138 but expressed CD3, HHV-8, and Epstein-Barr virus. Molecular genetic studies in this specimen revealed monoclonal rearrangements of the IgH gene. The diagnosis of PEL, solid variant, was made. Next-generation sequencing analysis of the tumorous and normal tissue detected a pathogenic germline mutation of the FAM175A gene and somatic mutations in BRCA2 and RAD51B (in both sarcoma and lymphoma specimens), and INPP4B and RICTOR (in lymphoma specimen only).

2nd Faculty of Medicine Charles University Prague Czech Republic

Biomedical Center Charles University Faculty of Medicine in Pilsen Pilsen Czech Republic; and

Bioptical Laboratory Pilsen Czech Republic

Department of Dermatology Medical Military Academy Saint Petersburg Russia

Department of Pathology Charles University Faculty of Medicine in Pilsen Pilsen Czech Republic

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Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2017:323–324.

Chadburn A, Hyjek E, Mathew S, et al. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am J Surg Pathol. 2004;28:1401–1416.

Knowles DM, Inghirami G, Ubriaco A, et al. Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus. Blood. 1989;73:792–799.

Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood. 1996;88:645–656.

Teruya-Feldstein J, Zauber P, Setsuda JE, et al. Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman's disease and primary effusion lymphoma. Lab Invest. 1998;78:1637–1642.

Pan ZG, Zhang QY, Lu ZB, et al. Extracavitary KSHV-associated large B-cell lymphoma: a distinct entity or a subtype of primary effusion lymphoma? study of 9 cases and review of an additional 43 cases. Am J Surg Pathol. 2012;36:1129–1140.

Zhang H, Yang XY, Hong T, et al. Kaposi sarcoma-associated herpesvirus (human herpesvirus type 8)-associated extracavitary lymphoma: report of a case in an HIV-positive patient with simultaneous kaposi sarcoma and a review of the literature. Acta Haematol. 2010;123:237–241.

Pielasinski U, Santonja C, Rodriguez-Pinilla SM, et al. Extracavitary primary effusion lymphoma presenting as a cutaneous tumor: a case report and literature review. J Cutan Pathol. 2014;41:745–753.

Aboulafia DM. HHV-8- and EBV-associated nonepidermotrophic large B-cell lymphoma presenting as a foot rash in a man with AIDS. AIDS Patient Care STDS. 2002;16:139–145.

Deloose ST, Smit LA, Pals FT, et al. High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma. Leukemia. 2005;19:851–855.

van Dongen JJ, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–2317.

Skalova A, Vanecek T, Martinek P, et al. Molecular profiling of mammary analog secretory carcinoma revealed a subset of tumors harboring a novel ETV6-RET translocation: report of 10 cases. Am J Surg Pathol. 2018;42:234–246.

Crane GM, Ambinder RF, Shirley CM, et al. HHV-8-positive and EBV-positive intravascular lymphoma: an unusual presentation of extracavitary primary effusion lymphoma. Am J Surg Pathol. 2014;38:426–432.

Crane GM, Xian RR, Burns KH, et al. Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma. J Cutan Pathol. 2014;41:928–935.

Cox FH, Helwig EB. Kaposi's sarcoma. Cancer. 1959;12:289–298.

Templeton AC. Kaposi's sarcoma. Pathol Annu. 1981;16:315–336.

Taylor JF, Templeton AC, Vogel CL, et al. Kaposi's sarcoma in Uganda: a clinico-pathological study. Int J Cancer. 1971;8:122–135.

Grayson W, Pantanowitz L. Histological variants of cutaneous Kaposi sarcoma. Diagn Pathol. 2008;3:31.

O'Connell KM. Kaposi's sarcoma: histopathological study of 159 cases from Malawi. J Clin Pathol. 1977;30:687–695.

Chapalain M, Goldman-Levy G, Kramkimel N, et al. Anaplastic Kaposi's sarcoma: 5 cases of a rare and aggressive type of Kaposi's sarcoma. Ann Dermatol Venereol. 2018;145:21–28.

Wang B, Matsuoka S, Ballif BA, et al. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007;316:1194–1198.

Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20:764–775.

Solyom S, Aressy B, Pylkas K, et al. Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions. Sci Transl Med. 2012;4:122ra123.

McKay JD, Truong T, Gaborieau V, et al. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS Genet. 2011;7:e1001333.

Ridge SA, Worwood M, Oscier D, et al. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci U S A. 1990;87:1377–1380.

Lamprecht B, Walter K, Kreher S, et al. Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nat Med. 2010;16:571–579.

Hartleben G, Muller C, Kramer A, et al. Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt's lymphoma. EMBO J. 2018;37:pii:e98589.

Jham BC, Ma T, Hu J, et al. Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma. PLoS One. 2011;6:e19103.

Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–792.

Miki Y, Katagiri T, Kasumi F, et al. Mutation analysis in the BRCA2 gene in primary breast cancers. Nat Genet. 1996;13:245–247.

Edwards SM, Kote-Jarai Z, Meitz J, et al. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet. 2003;72:1–12.

Schutte M, da Costa LT, Hahn SA, et al. Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. Proc Natl Acad Sci U S A. 1995;92:5950–5954.

Garcia-Marco JA, Caldas C, Price CM, et al. Frequent somatic deletion of the 13q12.3 locus encompassing BRCA2 in chronic lymphocytic leukemia. Blood. 1996;88:1568–1575.

Orr N, Lemnrau A, Cooke R, et al. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk. Nat Genet. 2012;44:1182–1184.

Nowacka-Zawisza M, Wisnik E, Wasilewski A, et al. Polymorphisms of homologous recombination RAD51, RAD51B, XRCC2, and XRCC3 genes and the risk of prostate cancer. Anal Cell Pathol (Amst). 2015;2015:828646.

Tokunaga E, Yamashita N, Kitao H, et al. Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer. Breast. 2016;25:62–68.

Kofuji S, Kimura H, Nakanishi H, et al. INPP4B is a PtdIns(3,4,5)P3 phosphatase that can act as a tumor suppressor. Cancer Discov. 2015;5:730–739.

Sarbassov DD, Ali SM, Kim DH, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004;14:1296–1302.

El Shamieh S, Saleh F, Moussa S, et al. RICTOR gene amplification is correlated with metastasis and therapeutic resistance in triple-negative breast cancer. Pharmacogenomics. 2018;19:757–760.

Cote GM, He J, Choy E. Next-generation sequencing for patients with sarcoma: a single center experience. Oncologist. 2018;23:234–242.

Ross JS, Wang K, Elkadi OR, et al. Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer. J Clin Pathol. 2014;67:772–776.