| Abstract|| |
ALK+ large B cell lymphoma (LBCL) is a very rare aggressive neoplasm. It accounts for less than 1% of diffuse large B cell lymphoma (DLBCL). This is a case report of ALK+ DLBCL in a 34-year-old woman with an ileocaecal mesenteric mass. Microscopically, the neoplastic cells were of high grade along with a spindle cell component. Immunohistochemistry revealed ALK+, MUM-1+, LCA+, Vimentin+, EMA+ and negative for CK 20, CK 7, neuroendocrine, melanocytic, muscle specific, and GIST panel markers. This case report, hence, presents the rarity of this tumor.
Keywords: Anaplastic lymphoma kinase positive large B cell lymphoma, CLTC-ALK gene, DLBCL, mesentery
|How to cite this article:|
Subramaniam A, Gnanasekaran D, Suruliraj S, Chinnusamy P. Anaplastic Lymphoma Kinase positive large B cell lymphoma of ileocaecal mesentery: A case report. Indian J Pathol Microbiol 2020;63:615-7
|How to cite this URL:|
Subramaniam A, Gnanasekaran D, Suruliraj S, Chinnusamy P. Anaplastic Lymphoma Kinase positive large B cell lymphoma of ileocaecal mesentery: A case report. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Nov 25];63:615-7. Available from: https://www.ijpmonline.org/text.asp?2020/63/4/615/299304
| Introduction|| |
According to WHO classification 2017, this ALK+ large B cell lymphoma (LBCL) is a very rare neoplasm comprising less than 1% of all diffuse LBCLs (DLBCLs) and it occurs more frequently in young men but spans all age groups. The tumor mainly involves lymph nodes or presents as a mediastinal mass. Extranodal involvement is also been reported.
Lymphoma cells show restricted granular cytoplasmic staining which is highly indicative of CLTC-ALK fusion protein. The tumors also strongly express EMA, plasma cell markers such as CD 138, VS38, PRDM1 and XBP1. This is negative for B cell lineage markers. IRF4/MUM1 is also positive. All cases are EBV and HHV8 negative.
The most frequent abnormality encountered in this type of lymphoma is t (2; 17) (p23; q23) responsible for a CLTC-ALK fusion protein. The patients with stages I and II are found to have longer survival than the patients with stage III/IV disease.
| Case History|| |
This 34-year-old young woman presented with abdominal pain for 10 days. She had dyspepsia, nausea and constipation on and off. On investigation, she was found to have a mass in the mesentery following which right hemicolectomy was done with a clinical/radiological impression of suspecting GIST [Figure 1] – top 2 images].
|Figure 1: Gross pictures of the tumor at the top. Bottom H and E pictures showing neoplastic cells in plasmacytoid appearance|
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The mass measured 12 × 7 × 6 cm in the mesentery. Cut sections appeared soft with areas of hemorrhage. Under the microscope, the tumor cells were of high grade with a distinct spindle cell component. Lymphocytic infiltration and necrotic areas were also noted. Adherent colonic mucosa, ileal wall and appendix were all free of tumor invasion. One lymph node out of 17 lymph nodes showed evidence of tumor invasion [Figure 1] – bottom images].
Immunohistochemistry was performed with an extended panel list. The tumor cells were positive for MUM-1, ALK-1 (cytoplasmic granular staining), LCA, Vimentin, Cyclin and EMA. Ki-67 index was about 80%-85%. The neoplastic cells were negative for all PLAP, SALL4, PAX-8, PAX-5, CD30, synatophysin, myogenin, CD56, CD3, CD43, CD20, CD117, CD34, CD23, Dog-1, CD21, CK, S-100, CD138, Tdt, Alphainhibin, Desmin, ER, SMA, HMB-45, Calretinin, cK7 and CK 20 [Figure 2] and [Figure 3].
The patient was given six cycles of chemotherapy with the CHOP regimen including Cyclophosphamide, Adriamycin, Vincristine and Prednisone but passed away after 8 months since diagnosis.
| Discussion|| |
ALK+ LBCL is a very rare type accounting for <1% of DLBCLs. It was first reported by Delsol et al. in 1997. All age groups are affected and it seems to have a male preponderance. Predominantly nodal involvement is seen in ALK+ DLBCL. But in the recent years, many extranodal presentations are increasingly reported.
Several studies revealed sinusoidal growth pattern along with the usual immunoblastic/plasmablastic differentiation. In our case, a prominent spindle cell pattern was also noted. The tumor cells were positive for ALK protein, LCA, MUM-1, Vimentin and EMA. The neoplastic cells showed ALK positivity in a cytoplasmic granular pattern suggesting the expression of Clarithin gene (CLTC-ALK protein).
The LCA was positive for tumor cells but CD 20 was negative and hence insensitive to Rituximab. The common genetic rearrangement seen is Clarithin-ALK in most of the cases and in a subset of 17% NPM-ALK fusion has also been reported. In another subset of cases, this tumor lacked the frequent 2; 5 translocation.
Cyclin D1 is generally overexpressed in mantle cell lymphoma and has been considered a critical oncogene in the tumor owing to its function in promoting the G1/S transition of the cell cycle. Cyclin D1 has also been found to be rarely overexpressed in some other tumors of the lymphoid and hematopoietic system including DLBCL this subset of cases in the literature substantiates the cyclin D1 expression in our case. The study by Wang and co-workers indicates that the expression of cyclin D1 suggests poor prognosis in patients with DLBCL.
The routine chemotherapy regimen for the ALK+ DLBCL patients is the CHOP (Cyclophosphamide, Adriamycin, Vincristine and Prednisone) or CHOEP regimen (CHOP with etoposide).
ALK+ LBCLs are a potential diagnostic pitfall for pathologists. Its diagnostic clues are that neoplastic cells are immunoblastic or/and plasmacytoid with prominent central nucleoli, positive for ALK, EMA, and some markers of late (plasma cell-like) B cell differentiation, such as CD138, VS38 and immunoglobulins, negative for B cell markers such as CD20 and CD79a. One of the studies has shown an unusual CD 33 expression in this tumor as well.
The diagnosis of this tumor is challenging due to its rarity, morphological resemblance to DLBCL, plasma cell neoplasms and epithelial neoplasms and ALK immunostain is not routinely performed in practice.
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Conflicts of interest
There are no conflicts of interest.
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Department of Pathology, GEM Hospital and Research Centre, Coimbatore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]