LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 2046
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size
IJPM is coming out with a Special issue on "Genitourinary & Gynecological pathology including Breast". Please submit your articles for these issues


 
  Table of Contents    
LETTERS TO EDITOR  
Year : 2019  |  Volume : 62  |  Issue : 4  |  Page : 632-634
EBV positive mucocutaneous ulcer of palate: A mimicker of malignancy


1 Department of Pathology, Artemis Hospitals, Gurugram, Haryana, India
2 Department of Head and Neck Surgery, Fortis Hospitals, New Delhi, India

Click here for correspondence address and email

Date of Web Publication14-Oct-2019
 

How to cite this article:
Goel D, Singh M. EBV positive mucocutaneous ulcer of palate: A mimicker of malignancy. Indian J Pathol Microbiol 2019;62:632-4

How to cite this URL:
Goel D, Singh M. EBV positive mucocutaneous ulcer of palate: A mimicker of malignancy. Indian J Pathol Microbiol [serial online] 2019 [cited 2019 Nov 18];62:632-4. Available from: http://www.ijpmonline.org/text.asp?2019/62/4/632/269072




Editor,

Epstein--Barr virus (EBV) is a ubiquitous herpes virus. After primary infection at an early age, EBV establishes latent infection in B-cells. A higher EBV prevalence rate is found in immunosuppressed compared with healthy individuals. EBV is able to elicit B-cell transformation and proliferation, which is kept in check by T-cell immune surveillance. Iatrogenic immunosuppression (IS) for autoimmune disorders, the post-transplant setting, as well as age-related immunosenescence can lead to the emergence of EBV-positive B-cell lymphoproliferative disorders (B-LPDs).[1]

EBV-positive mucocutaneous ulcer (EBVMCU) is a newly recognized entity in 2017 revised edition of World Health Organization (WHO) classification of lymphoid neoplasms. Dojcinov et al. reported this entity for the first time in 2010. In a series of 26 patients, 17 were associated with age-related immunosenescence and nine were on IS drugs. The pathologic features were identical regardless of the anatomic site or cause of immunosuppression. Forty-five percent patients regressed spontaneously with no treatment and 15% were characterized by a relapsing and remitting course. All of the iatrogenic lesions, with available follow-up responded to reduction of IS.[2]

Since then, EBVMCU has been reported in many clinical settings other than IS drugs and immunosenescence. Drugs such as methotrexate, azathioprine, cyclosporine, and mycophenolate has been reported as the cause of immunosuppression.[3],[4],[5] Hart et al. reported EBVMCU in solid organ transplant recipients. In a cohort of 70 transplant recipients with EBV LPDs, they observed seven patients with EBVMCU.[6]

A 76-year-old male patient came to our hospital for review of surgical biopsy slides. He had a palatal ulcer since 4 weeks for which he first underwent a biopsy in his hometown. The biopsy was reported as poorly differentiated carcinoma. The biopsy was again reviewed at other hospital and was reported the same on morphological features. On the basis of these reports, patient underwent wide local excision with lymph node resection. All the slides were submitted for review. The patient gave history of intake of IS drugs. He was taking azathioprine since 4 years and before that he was on methotrexate for 3 years as he was suffering from rheumatoid arthritis.

Microscopy from resected specimen revealed mucosal ulceration with pseudoepitheliomatous hyperplasia of adjacent epithelium. Beneath the ulcer, there was dense polymporphous infiltrate with variable number of lymphocytes, plasma cells, and eosinophils [Figure 1]a. There are scattered large transformed cells resembling Hodgkin/Reed—Sternberg-like cells (R--S) or atypical immunoblasts [Figure 1]b. Areas of apoptotic debris and necrosis were seen. The infiltrate was reaching upto the bone, however bony infiltration was not seen. Immunohistochemistry (IHC) revealed positivity for CD3 [Figure 1]c and CD8 [Figure 1]d in background lymphoid cells. Positivity for CD20, CD30 [Figure 1]e, EBV-LMP1 [Figure 1]f, Pax5 [Figure 1]g, MUM1 [Figure 1]h was noted in the large cells. They were immunonegative for CD15, Alk-1, and CD68. CK and p40 [Figure 1]i were also negative. All the lymph nodes resected were reactive. The initial biopsy was also reviewed. Fragmented biopsy showed granulation tissue with polymorphous infiltrate and scattered atypical R--S like/immunoblasts, which were mistaken for malignant epithelial cells [Figure 2]. These cells showed similar immunoprofile as described above. Final diagnosis of EBVMCU was rendered.
Figure 1: (a): Ulcer with polymorphous infiltrate at the base. (H and E × 100), (b): Scattered large transformed cells. (H and E × 400), (c): Backgound lymphocytes are immunopositive for CD3 (× 200), (d): Backgound T- lymphocytes are mainly immunopositive for CD8 (× 200), (e): Scattered large transformed cells show positivity for CD30 (× 400), (f): Scattered large transformed cells show positivity for EBV-LMP1 (× 400), (g): Nuclear positivity in large cells for Pax5 (× 200), (h): Nuclear positivity in large cells for MUM1 (× 400), (i): Large cells are immunonegative for p40. (× 200)

Click here to view
Figure 2: Initial biopsy with dense polymorphous infiltrate and scattered large cells. (Red arrows: H and E × 400)

Click here to view


EBVMCU were first identified as a distinct clinicopathological entity in 2010. Dojcinov et al. reported a study of 26 cases of ulcerative lesions arising in the skin, oropharynx, and GIT. These lesions displayed an indolent self-limited course, often regressing spontaneously or with reduction of immunosuppression, and with no reports of progression to disseminated disease.[2]

This is the third case report from India. Priyanka et al. reported a case of 59-year-old female on methotrexate having a lesion in lower gingivobuccal sulcus.[3] Arneja et al. described a case of 70-year-old male on azathioprine presented with anal ulcer.[4] We report a case of palatal ulcer that had been on methotrexate initially and azathioprine afterwards.

The main differential diagnosis is with classical Hodgkin lymphoma (CHL), which also shows similar kind of infiltrate. But CHL almost always presents as mass lesion, which is not seen in our case. Moreover, lymph nodal involvement was also absent in present case. CHL presenting as extranodal disease in the absence of nodal involvement is extremely rare, and the presence of an intact B-cell program with CD45 expression in EBVMCU allows distinction.

Poorly differentiated carcinoma came into differential diagnosis because of scant and fragmented nature of biopsy with exuberant granulation tissue formation and scattered large atypical cells. The atypical cells in carcinoma usually form nests and islands surrounded by desmoplastic stroma. In this case, the cells were singly scattered in a polymorphous background. There were binucleate and multilobated forms. Lack of availability of IHC, scant nature of tissue, and lack of awareness of this entity were the possible causes of misinterpretation. Poorly differentiated carcinoma in a setting of IS has a poor prognosis. The patient in present scenario not only required surgery but also adjuvant radiation therapy, in contrast to the benign course of EBVMCU. Au et al. studied head and neck EBVMCU and observed that 96.6% of patients with follow-up greater than 2 months achieved complete remission with conservative management.[7]

EBV-positive B- LPDs is also one of the close differentials in which the cytologic composition and phenotype is indistinguishable from EBVMCU. Some are identical to EBV + diffuse large B- cell lymphoma (DLBCL). Clinical features are of paramount importance in making the distinction, particularly the localized nature of EBVMCU and absence of a mass lesion. Peripheral blood EBV-DNA load may also be useful, and a putative diagnosis of EBVMCU should be questioned if elevated. However, in this patient, serum EBV-DNA was neither done at the time of initial biopsy nor at the time of resection. Pathologically, the sharp circumscription of EBVMCU with a band of small T cells at the base of the lesion helped differentiation from the more infiltrative pattern seen with polymorphic B-LPD and EBV + DLBCL. Immunostaining for EBV typically reveals a type II or type III latency pattern. Monoclonal immunoglobulin gene rearrangement can be identified in around half of cases.[8]

Age-associated EBVMCU has a high likelihood of spontaneous remission without treatment. Reduction in immunosuppression is preferred in patients on IS drugs. Persistent and progressive disease may require treatment with rituximab or radiotherapy.[9] Immunosuppression was reduced in our patient to prevent involvement of any other site. No adjuvant radiotherapy given. Patient was suggested regular follow-up. After 3 months follow-up, no disease progression is seen.

To conclude, EBVMCU is a newly recognized entity with a self-limiting course. Awareness of this entity, proper clinical history, and ancillary studies can avoid misinterpretation and over management. Reporting pathologist as well as clinician should be aware of this rare clinicopathological entity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Ambrosio MR, Rocca BJ, Ginori A, Mourmouras V, Amato T, et al. A look into the evolution of Epstein-Barr virus induced lymphoproliferative disorders: A case study. Am J Clin Pathol 2005;144:817-22.  Back to cited text no. 1
    
2.
Dojcinov SD, Venkataraman G, Raffeld M, Pittaluga S, Jaffe ES. EBV positive mucocutaneous ulcer--A study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010;34:405-17.  Back to cited text no. 2
    
3.
Ravi PY, Sigamani E, Jeelani Y, Manipadam MT. Methotrexate-associated Epstein-Barr virus mucocutaneous ulcer: A case report and review of literature. Indian J Pathol Microbiol 2018;61:255-7.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Arneja S, Balsara KP, Modhkarkar S. Azathioprine induced Epstein- Barr virus positive mucocutaneous ulcer: A case report. J Mod Hum Pathol 2018;3:1-3.  Back to cited text no. 4
    
5.
Kanemitsu M, John D, Lim A, Jaffe ES, Aoki J. Clonal Epstein-Barr virus-positive mucocutaneous ulcer mimicking a mature B-cell lymphoma in a patient with mycophenolate-induced immune suppression. Leuk Lymphoma 2015;56:1908-10.  Back to cited text no. 5
    
6.
Hart M, Thakral B, Yohe S, Balfour HH, Singh C, Spears M, et al. EBV-positive mucocutaneous ulcer in organ transplant recipients: A localized indolent posttransplant lymphoproliferative disorder. Am J Surg Pathol 2014;38:1522-9.  Back to cited text no. 6
    
7.
Au JK, Said JW, Sepahdari AR, St John MA. Head and neck Epstein-Barr virus mucocutaneous ulcer: Case report and literature review. Laryngoscope 2016;126:2500-4.  Back to cited text no. 7
    
8.
Kuppers R. B-cells under the influence: Transformation of B-cells by Epstein-Barr virus. Nat Rev Immunol 2003;3:801-12.  Back to cited text no. 8
    
9.
Roberts TK, Chen X, Liao JJ. Diagnostic and therapeutic challenges of EBV-positive mucocutaneous ulcer: A case report and systematic review of the literature. Exp Hematol Oncol 2016;5:13.  Back to cited text no. 9
    

Top
Correspondence Address:
Deepa Goel
Artemis Hospitals, Sector - 34, Gurugram, Haryana
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_51_19

Rights and Permissions


    Figures

  [Figure 1], [Figure 2]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  


    References
    Article Figures

 Article Access Statistics
    Viewed102    
    Printed2    
    Emailed0    
    PDF Downloaded12    
    Comments [Add]    

Recommend this journal