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CASE REPORT
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Signet ring cell lymphoma of follicular type with BCL2 gene rearrangement: A rare case with a short review of literature


1 Department of Pathology and Lab Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
2 Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
3 Department of Cytogenetics, Tata Memorial Center, Kolkata, West Bengal, India

Date of Submission30-Aug-2019
Date of Decision30-Aug-2019
Date of Acceptance24-Jan-2020
Date of Web Publication22-Jun-2022

Correspondence Address:
Mukund Sable,
Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_676_19

 > Abstract 


A case of signet ring cell lymphoma of presacral lymph node is reported. The patient was diagnosed as follicular lymphoma on the basis of clinical and laboratory features, including immunohistochemistry (IHC) and gene rearrangement studies. Light microscopy examination showed neoplastic atypical cells with signet ring cell morphology in core biopsy of lymph node that stained for B-cell markers by IHC. In addition, the neoplastic cells expressed CD20, CD10, BCL-2, and BCL-6, indicating follicular center origin. Fluorescence in situ hybridization study demonstrated BCL2 gene arrangement. Especially in the case of deep-seated intra-abdominal lymph nodes with atypical presentation, the differential diagnosis arises with nonhemopoietic tumors, and this needs to be distinguished by specific immunostaining and gene arrangement studies.

Keywords: BCL2, fluorescence in situ hybridization, follicular lymphoma, signet ring cells



How to cite this URL:
Mishra P, Adhya AK, Kar M, Parihar M, Samal S, Sable M. Signet ring cell lymphoma of follicular type with BCL2 gene rearrangement: A rare case with a short review of literature. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 2]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=347791




 > Introduction Top


Signet ring cell lymphoma (SCL) is an uncommon variant of non-Hodgkin lymphoma (NHL). Although SCL is not a distinct clinicopathological entity according to the WHO classification for hematolymphoid tumors, different subtypes of lymphoma display it as a morphological variant. Within the B-cell lymphomas, SCL is a rare variant and commonly seen in follicular lymphoma (FL).[1] Signet ring cell morphology could be deceptive, especially in deep-seated lymphoid tissues such as intra-abdominal and retroperitoneal lymph nodes and extranodal sites. The cytoplasm may appear clear or eosinophilic mimicking an epithelial malignancy: signet ring cell carcinoma in needle core biopsies. Due to its rarity, the possibility of SCL should be kept in mind, which can be further substantiated by immunohistochemistry (IHC) and molecular analysis. Herein, we present a case of SCL with follicular type in a presacral lymph node, which was confirmed by IHC and with BCL2 gene rearrangement.


 > Case Report Top


A 64-year-old male patient presented with weakness for 3 months. There was no history of fever or weight loss. Ultrasonography of the abdomen revealed a well-circumscribed large cystic lesion measuring 8 cm × 7 cm × 6.5 cm posterior to the urinary bladder. Magnetic resonance imaging of the abdomen and pelvis revealed a well-defined nonenhancing presacral mass in retroperitoneum with cystic changes. Fluorodeoxyglucose (FDG) positron-emission tomography (PET) study showed a large presacral lymph nodal mass measuring 9.8 cm × 7.7 cm × 6.5 cm (SUVmax 18.3). The mass abuts upper part of the rectum focally but the fat plane between mass and urinary bladder is well maintained. Few peripancreatic, retropancreatic, paraaortic, left common iliac, and mesenteric nodes were seen, the largest node was measuring 2.3 cm × 2.1 cm. In addition, spleen showed heterogeneously increased FDG uptake. Although there was prostate enlargement, it did not show any focus of FDG avidity.

Hemogram revealed bicytopenia with hemoglobin level 8.9 g/dl, peripheral smear examination did not reveal any atypical lymphoid cells. The serum lactate dehydrogenase level was 282.4 U/L. In addition, serological markers for hepatitis B infection were positive, whereas negative for HIV and hepatitis C infection. Ultrasonography-guided trucut biopsy from the presacral mass was done.

Histopathology

Histopathological study of the trucut biopsy revealed linear cores of tissue showing atypical lymphoid cells arranged in vague nodules [Figure 1]a. These lymphoid cells were small to intermediate size with cleaved nucleus [Figure 1]b. Scattered centroblast is also seen. In addition, many cells showing eccentrically placed nuclei and vacuolated cytoplasm indicating signet ring cell-like morphology were noted within the nodules [Figure 1]c.
Figure 1: (a) Linear cores of tissue showing proliferation of atypical lymphoid cells (H and E, ×40); (b and c) Vacuolated signet ring cells interspersed within the nonvacuolated lymphoma cells. (H and E, ×200, ×400); (d) Atypical lymphoid cells showing immunopositivity for CD20 (IHC, ×100), (e) CD10 (IHC, ×100), (f) BCL2 (IHC, ×100), and (g) immunonegative for Cyclin D1 (IHC, ×100). (h) Atypical lymphoid cells are also positive for BCL6 (IHC, ×100), (i) CD23 highlighted the follicular dendritic cells (IHC, ×100) (j) MIB-1 index approximately 55%–60% (IHC, ×100) (k) fluorescence in situ hybridization showing BCL2 rearrangement.

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On IHC, the atypical lymphoid cells and the signet ring like cells were diffusely immunopositive for CD20 [Figure 1]d, CD79a, CD10 [Figure 1]e, BCL-2 [Figure 1]f, and BCL-6 [Figure 1]h, whereas immunonegative for CD3, CD5, MUM1, CD30, and Cyclin-D1 [Figure 1]g. CD23 highlighted the follicular dendritic cells [Figure 1]i. Epithelial (pan-cytokeratin) and mesenchymal markers (desmin) were negative. The proliferative index was 55%–60% [Figure 1]j. To exclude the possibility of adipocytes, immunostain for S100 was negative. Special stain for mucicaramine was negative. Based on histomorphology and IHC results, a diagnosis of FL, Grade 3, signet ring cell variant was rendered. Fluorescence in situ hybridization analysis demonstrated BCL2 gene rearrangement on chromosome 18, band q21 in 100% of cells [Figure 1]k. There was no evidence of bone marrow involvement. Ann Arbor stage was A-Abscence of B symptoms S-Spleen involvement (IIIAS), and ECOG score was 0–1.

The patient was started with R-CHOP regimen. After completion of six cycles of chemotherapy and 36 GY of radiation (20 cycles), PET/computed tomography showed significant decrease in the size and metabolic activity of the presacral lymph node suggestive of significant response to chemotherapy. No metabolic activity was seen in the spleen and other lymph nodes [Figure 2]. The patient is doing well, and there is no recurrence after 14 months of therapy.
Figure 2: Pre-and post-treatment positron-emission tomography -computed tomography scan showing significant decrease in uptake in lymph node with significant reduction in size with absence of new lesion

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 > Discussion Top


SCL is a rare morphological variant of NHL first noticed by Kim et al.[2] Although it is not a separate entity, the signet ring cell morphology was described in large variety of B-cell and T-cell lymphomas, including FL,[1] diffuse large B-cell lymphoma,[3] small lymphocytic lymphoma,[4] mucosa associated lymphoid tissue lymphoma,[5] multiple myeloma,[6] T-cell lymphoma,[7] and anaplastic large cell lymphoma.[8]

On review of the English literature, 38 cases[2],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25] (including the present case) of SCL FL type were described till date. Detailed clinicopathological features of all the cases are summarized in [Table 1]. Mostly, the cases that are described are in the form of case reports and short series. In majority of cases, the site of involvement was lymph node. Although extranodal sites such as thyroid, skin, uterus, and small bowel are described, they are uncommon sites.[16],[17],[20],[21] Age of presentation ranged from 23 to 81 years, majority of the patients were above 50 years.
Table 1: Clinicopathological features of signet ring cell lymphoma . follicular lymphoma published in the English literature

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All the cases reported in the past two decades had IHC results and showed positivity for CD20, CD10, and BCL2, whereas negative for CD5, Cyclin D1, and T-cell markers. However, the BCL2 gene rearrangement was seen in only four cases, including the present case [Table 1]. In the series by Zhang et al.,[24] who reported five cases of FL with signet morphology, four cases lacked IgH/BCL2 translocation although BCL2 immunoexpression was seen in all. Interesting to note that the case reported by Sarro et al.,[20] showed FL Grade 1 of the cervical node but without a signet ring cell morphology. The disease recurred after 5 years as an intramural uterine tumor, which showed medium-to-large-sized atypical lymphoid cells with signet ring cell morphology and was diagnosed as FL, Grade 1–2. However, both biopsies showed BCL2 rearrangement.

Most of the reported cases are on tissue sections; however, Wang et al.[23] reported the largest series of SCL in fine-needle aspiration samples. The cytologic features that favored a diagnosis were the signet ring cells in a background of nonvacuolated lymphomatous cells, lymphoglandular bodies, and cytoplasmic rings. In cytology preparations, the signet cells contained a single, intracytoplasmic vacuole, whereas minority of cells contained more than two vacuoles that indented the nucleus into a scalloped or stellate configuration. They highlighted the fact that the diagnostic clues of SCL on cytology were the similarity in nuclear details between signet ring cells and surrounding nonvacuolated lymphoid cells.

Ultrastructural and IHC studies affirmed that both B- and T-cell lymphomas demonstrated signet ring cell morphology due to aberrant membrane cycling and the accumulation of intracellular immunoglobulins. In B-cell lymphomas, the signet ring cells either have a clear vacuolated cytoplasm due to accumulation of immunoglobulin IgG or eosinophilic cytoplasm containing Russell body-like immunoglobulin IgM (kappa type).[2]

It is important for the surgical pathologist to keep in mind, the signet ring cell morphology in diagnosing lymphomas as this morphology is infrequently encountered in lymphomas. Signet ring cells are quite deceptive and can be seen in various neoplasms such as epithelial, mesenchymal, hematolymphoid, and melanomas. It is imperative to distinguish these lesions as the management varies. The clue to diagnosis is a meticulous observation of the morphologic features. The features that favor a diagnosis of lymphoma are nodular growth pattern even in small areas and angulated or cleaved neoplastic cells scattered among vacuolated or immunoglobulin containing signet ring cells.

To conclude, though signet ring cell morphology is commonly observed in carcinoma, it is important to speculate the rare possibility of signet ring cell morphology in diagnosing lymphomas mainly at extranodal sites. Morphology with judicious use of antibody and molecular analysis are helpful in rendering a correct diagnosis.

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008.  Back to cited text no. 1
    
2.
Kim H, Dorfman RF, Rappaport H. Signet ring cell lymphoma. A rare morphologic and functional expression of nodular (follicular) lymphoma. Am J Surg Pathol 1978;2:119-32.  Back to cited text no. 2
    
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Dardick I, Srinivasan R, Al-Jabi M. Signet-ring cell variant of large cell lymphoma. Ultrastruct Pathol 1983;5:195-200.  Back to cited text no. 3
    
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Ramnani D, Lindberg G, Gokaslan ST, Albores-Saavedra J. Signet-ring cell variant of small lymphocytic lymphoma with a prominent sinusoidal pattern. Ann Diagn Pathol 1999;3:220-6.  Back to cited text no. 4
    
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Zamboni G, Franzin G, Scarpa A, Bonetti F, Pea M, Mariuzzi GM, et al. Carcinoma-like signet-ring cells in gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Am J Surg Pathol 1996;20:588-98.  Back to cited text no. 5
    
6.
Dorfman RF. Multiple myeloma showing signet-ring cell change. Histopathology 1991;18:577-8.  Back to cited text no. 6
    
7.
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8.
Falini B, Liso A, Pasqualucci L, Flenghi L, Ascani S, Pileri S, et al. CD30+ anaplastic large-cell lymphoma, null type, with signet-ring appearance. Histopathology 1997;30:90-2.  Back to cited text no. 8
    
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van den Tweel JG, Taylor CR, Parker JW, Lukes RJ. Immunoglobulin inclusions in non-Hodgkin's lymphomas. Am J Clin Pathol 1978;69:306-13.  Back to cited text no. 9
    
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Moir DH. Signet ring cell lymphoma: A case report. Pathology 1980;12:119-22.  Back to cited text no. 10
    
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Iossifides I, Mackay B, Butler JJ. Signet-ring cell lymphoma. Ultrastruct Pathol 1980;1:511-7.  Back to cited text no. 11
    
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Harris M, Eyden B, Read G. Signet ring cell lymphoma: A rare variant of follicular lymphoma. J Clin Pathol 1981;34:884-91.  Back to cited text no. 12
    
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Pileri S, Serra L, Govoni E, Martinelli G. Signet ring cell lymphoma: A case report. Histopathology 1981;5:165-73.  Back to cited text no. 13
    
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Navas-Palacios JJ, Valdes MD, Lahuerta-Palacios JJ. Signet-ring cell lymphoma. Ultrastructural and immunohistochemical features of three varieties. Cancer 1983;52:1613-23.  Back to cited text no. 14
    
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Silberman S, Fresco R, Steinecker PH. Signet ring cell lymphoma. A report of a case and review of the literature. Am J Clin Pathol 1984;81:358-63.  Back to cited text no. 15
    
16.
Allevato PA, Kini SR, Rebuck JW, Miller JM, Hamburger JI. Signet ring cell lymphoma of the thyroid: A case report. Hum Pathol 1985;16:1066-8.  Back to cited text no. 16
    
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Hanna W, Kahn HJ, From L. Signet ring lymphoma of the skin: Ultrastructural and immunohistochemical features. J Am Acad Dermatol 1986;14:344-50.  Back to cited text no. 17
    
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Nagasaki A, Oshiro A, Miyagi T, Sakihara M, Oshima K, Kikuchi M, et al. Signet-ring cell lymphoma. Intern Med 2003;42:1055-6.  Back to cited text no. 18
    
19.
Coffing BN, Lim MS. Signet ring cell lymphoma in a patient with elevated CA-125. J Clin Oncol 2011;29:e416-8.  Back to cited text no. 19
    
20.
Sarro R, Fiche M, Bisig B, Ketterer N, Benhattar J, Achtari C, et al. An unusual uterine tumor with signet ring cell features. Int J Gynecol Pathol 2012;31:236-41.  Back to cited text no. 20
    
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Basir N, Bickle IC, Telisinghe PU, Abdullah MS, Chong VH. Signet ring cell lymphoma of the small bowel: A case report. Oman Med J 2012;27:491-3.  Back to cited text no. 21
    
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Krause JR. Signet ring lymphoma: A potential diagnostic mishap. Proc (Bayl Univ Med Cent) 2013;26:293-4.  Back to cited text no. 22
    
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Wang J, Katz RL, Stewart J, Landon G, Guo M, Gong Y. Fine-needle aspiration diagnosis of lymphomas with signet ring cell features: Potential pitfalls and solutions. Cancer Cytopathol 2013;121:525-32.  Back to cited text no. 23
    
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Zhang S, Sun J, Fang Y, Nassiri M, Liu L, Zhou J, et al. Signet-ring cell lymphoma: Clinicopathologic, immunohistochemical, and fluorescence in situ hybridization studies of 7 cases. Ann Diagn Pathol 2017;26:38-42.  Back to cited text no. 24
    
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Gore CR, Panicker NK, Kumar H, Buch A, Chandanwale SS. A rare case of signet ring cell lymphoma: Diagnosis aided by immunofluorescent staining. J Cytol 2017;34:56-8.  Back to cited text no. 25
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