A 65-year-old gentleman presented with left groin swelling over the course of two months. Physical exam revealed nontender left inguinal adenopathy, and computed tomography scans detected multiple lymph nodes in the mesenteric, aortocaval, and right common iliac regions. An excisional lymph node biopsy was performed. Pathologic evaluation demonstrated follicular center site which stained positive for PAX5, CD20, CD10, Bcl-2, Bcl-6, and mantle zone cells. These findings demonstrated CCND1 and CD5 positivity, suggesting composite lymphoma comprising follicular lymphoma (FL) with
Composite lymphoma (CL) is defined by two or more morphologically and immunophenotypically distinct lymphomas observed within the same anatomic site [
MCL and FL composite lymphomas.
Case number | Age | Involvement | Immunohistochemistry staining | Treatment | Follow-up | Ref |
---|---|---|---|---|---|---|
Gender | ||||||
1 | 66 F | Waldeyer ring |
MCL: CD5+, CD20+, IgD+, cyclinD1+, Bcl-2+, CD3− |
Corticosteroid | PET scan every 3–6 months | [ |
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2 | M | Ocular adnexa | NA | NA | Poor prognosis mentioned | [ |
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3 | 84 F | Spleen | FL: CD20+, CD23+, Bcl-6+, CD5−, CD43−, Bcl-2− |
Splenectomy |
9 months after splenectomy, CT scan showed intra-abdominal lymphadenopathy and patient died from unknown cause 13 months later | [ |
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4 | 70 F | Cervical LN |
CD20+, CD3−, cyclinD1− |
No chemotherapy | CT of chest and abdomen showed no evidence of lymphadenopathy or hepatosplenomegaly | [ |
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5 | 65 M | Inguinal LN | FL: CD20+, CD79a+, CD10+, Bcl-2+, CD5−, CD230, cyclinD1−, p27+ |
Splenectomy | MCL caused disease progression into spleen. One year after splenectomy, it achieved stable disease | [ |
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6 | 58 F | Mesenteric LN |
MCL: CD5+, CD20+, CD43+ |
22 cycles of chemotherapy over 2 years | Complete remission | [ |
MCL
Case number | Histology | Immunohistochemistry |
FISH/southern blot/PCR | Tissue microdissection | Molecular technique to determine clonal relationships | Results interpretation | Ref |
---|---|---|---|---|---|---|---|
1 | MCL: |
|
NA | Not done | Not done | Not known | [ |
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2 | MCL: |
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t |
Performed | IgH PCR FR1 FR3 JH | Clonally related | [ |
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3 | MCL: |
|
t |
Performed | IgH PCR FR2 D1–6 IgL PCR Vk/Kde | Clonally related | [ |
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4 | MCL: |
|
NA | Not done | Not Done | Not known | [ |
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5 | MCL: |
|
t |
Performed | PCR for IgH | Clonally related | [ |
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6 | MCL: |
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t |
Performed | PCR for IgH | Clonally related | [ |
A 65-year-old male with a history of gastric bypass surgery and left inguinal hernia repair presented with left groin swelling for two months without any other associated symptoms. He initially presented with an enlarged, palpable, nontender left inguinal lymph node measuring 1 × 1.5 cm. Initial laboratory results, including complete blood count, complete metabolic panel, lactate dehydrogenase, and beta-2-microglobulin, were normal. Computed tomography scan detected multiple lymph nodes in the mesenteric, aortocaval, and right common iliac lymph nodes measuring up to 13 mm in diameter. At the time of surgical evaluation, the inguinal lymph node had regressed and was difficult to pinpoint by physical exam. He, therefore, underwent excisional biopsy of a mesenteric lymph node visible on the CT scan (Figure
H & E and immunohistochemical staining of follicular components. Hematoxylin and eosin stained sections showed numerous neoplastic follicles occupying almost the entire lymph node, effacing the normal nodal architecture extending from the cortex to the hilum, and invading beyond the capsule ((a) 4x). The neoplastic follicles consist of small centrocytes with ovoid shape, small angulated nuclei, clumped chromatin, and inconspicuous or absent nucleoli. Rare intermixed centroblasts are seen ((b) 20x and (c) 40 xs). Immunohistochemical staining revealed the germinal center cells expressing the pan B-cell marker CD20 ((d) 10x) in addition to germinal center-associated markers CD10 ((e) 10x), BCL-6 ((f) 10x), and BCL-2 ((g) 10x). The collective histologic and immunophenotype findings indicated a follicular lymphoma, grade 1 of 3.
Immunohistochemical staining of
FL is one of the common non-Hodgkin lymphomas with an estimated incidence of 3.18 cases per 100,000 people in the USA [
MCL is an aggressive and relatively rare lymphoma with an annual incidence of approximately 4–8 cases per million in the USA [
Clinical features, follow-up, and management in
Case number | Age | Site of biopsy | Management | Follow-up | Status | CD5 | Concurrent malignancy | Ref |
---|---|---|---|---|---|---|---|---|
Sex | ||||||||
1 | 70 M | Cervical lymph node | W&W | 4 years | Overt MCL | − | [ | |
2 | 65 F | LN | Chemotherapy | 0.5 years | AND | − | [ | |
3 | 65 M | Appendix | W&W | 4 years | Overt MCL | + | [ | |
4 | 66 M | Pelvic LN | W&W | 4 years | Overt MCL | + | Prostate cancer | [ |
5 | 68 M | LN, mediastinal | W&W | 1 year | AWD | Not tested | [ | |
6 | 82 M | Oropharynx | W&W | 3 years | AWD | + | CLL/SLL | [ |
7 | 82 M | Lymph node | Chemotherapy | 1.5 years | AND | + | CLL/SLL | [ |
8 | 80 M | Inguinal LN | Chemotherapy | N/A | N/A | + | CLL/SLL | [ |
9 | 42 F | Cervical lymph node | W&W | 1 year | Alive with no disease (AND) | − | Breast cancer | [ |
10 | 78 F | Lacrimal gland | Not available (NA) | NA | NA | + | NA | [ |
11 | 42 M | Supraclavicular LN | Radiotherapy | 1.7 years | AND | − | Castleman disease | [ |
12 | 58 M | Intestine | Chemotherapy | 1.4 years | AND | + | none | [ |
13 | 42 F | LN, axillary/inguinal, GIT | Chemotherapy | 6 years | AND | + | [ | |
14 | 70 F | LN, submandibular | W&W | 12 years | AWD in Peripheral blood (PB) | + | Nonspecific granulomas | [ |
15 | 59 M | Cervical lymph node | W&W | 5 years | AND | − | Papillary thyroid cancer | [ |
16 | 80 M | Cervical LN | Chemotherapy | 1.5 years | Died | + | FL | [ |
17 | 65 F | Intramammary LN | Chemotherapy | 5 years | AND | + | FL | [ |
18 | 65 M | Appendix | W&W | 4 years | MCL | + | NA | [ |
19 | 68 M | Mediastinal LN | W&W | 1 year | AND | NA | — | [ |
20 | 41 F | Inguinal lymph node (LN) | Watch and Wait (W&W) | 19.5 years | Alive with disease (AWD) | − | none | [ |
21 | 72 F | Cervical lymph node | Radiotherapy | 2 years | AND | + | Breast cancer | [ |
22 | 34 M | Left supraclavicular LN | Chemotherapy | 1 month | Died | + | FL | [ |
W&W: watch and wait.
AND: alive with no disease.
AWD: alive with disease.
NA: nonavailable.
CLL: chronic lymphocytic leukemia.
SLL: small lymphocytic lymphoma.
LN: lymph node.
GIT: gastrointestinal tract.
Most of MCLIS cells can be divided into two groups: CD5-negative and CD5-positive MCLIS. CD5-negative MCLIS can be typically seen in younger patients, where it often presents with nodal involvement and requires no treatment in most cases. On the other hand, CD5-positive MCLIS is associated with older age, extranodal involvement, and other lymphomas. Patients with CD5-positive MCLIS are more likely to require treatment. Interestingly, no difference in survival has been noted between these two groups [
The t(11; 14) (q13; q32) rearrangement juxtaposing the protooncogene CCND1 to the immunoglobulin heavy chain (IGH) complex is considered a pivotal event in the development of MCL. This translocation occurs within the bone marrow during pre-B stage differentiation with V (D) J recombination of the IGH variable region (IGHV) [
No guidelines have been established for the staging and management of MCLIS. The majority of patients with MCLIS will not develop overt MCL. Therefore, they can be followed up for long periods without treatment [
The significance of MCLIS still remains obscure. At this moment, it is unknown whether MCLIS represents true precursor lesions that will progress to an overt lymphoma or are incidental findings with a low chance of progression. Composite lymphoma with FL and MCLIS can pose diagnostic and therapeutic challenges. However, with new advances in molecular pathology and lymphoma genomics, we have more opportunities to investigate these rare diseases and gain novel insights into their biology in order to benefit the management of affected patients.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors declare that there is no conflict of interests regarding the publishing of this paper.
Josephine Taverna and Anju Nair contributed equally to this work and share first authorship.