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Year : 2022  |  Volume : 65  |  Issue : 2  |  Page : 503-505
Follicular lymphoma behind a facade of Castleman disease, a diagnostic challenge

1 Department of Pathology, The University of Jordan, Amman, Jordan
2 Department of Hematology and Medical Oncology, The University of Jordan, Amman, Jordan

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Date of Submission07-Aug-2020
Date of Decision18-Apr-2021
Date of Acceptance23-Apr-2021
Date of Web Publication14-Apr-2022

How to cite this article:
Aladily TN, Al-Fararjeh F, Bustami N, Mansour AT. Follicular lymphoma behind a facade of Castleman disease, a diagnostic challenge. Indian J Pathol Microbiol 2022;65:503-5

How to cite this URL:
Aladily TN, Al-Fararjeh F, Bustami N, Mansour AT. Follicular lymphoma behind a facade of Castleman disease, a diagnostic challenge. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Dec 4];65:503-5. Available from:

Dear Editor,

We describe a case of follicular lymphoma (FL) in which the histomorphology was potentially mistaken as hyaline-vascular type of Castleman disease (HV-CD). A 70-year-old man was incidentally found to have cervical, axillary, and inguinal lymphadenopathy during the physical examination for a suspected deep vein thrombosis in the lower limbs. Imaging studies revealed additional lymphadenopathies above and below the diaphragm. The patient underwent excisional biopsy of cervical lymph nodes, where the largest one was 1.5 cm in diameter. Microscopically, the architecture was disturbed by proliferating follicles of variable sizes, many of which were atretic. The entire follicles lacked normal polarization and the presence of tangible-body macrophages. The mantle zone of many follicles was preserved and exhibited concentric Indian-file arrangement as well as the presence of penetrating vessels into germinal centers and occasional sclerosis, characteristic of “onion skinning” and “lollipop” lesions of HV-CD. In addition, some follicles harbored two or more germinal centers “twinning” [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e. The follicular dendritic cells (FDC) were readily discernible and appeared dysplastic in very few follicles [Figure 1]f. The interfollicular area was expanded by small monotonous lymphocytes of cleaved shape and exhibited increased vascularity, which was also evident by immunohistochemistry staining for smooth muscle actin [Figure 1]k, CD34, CD105. Plasma cells were not increased and there was no large cell transformation.
Figure 1: Histologic findings. (a) Medium power view of a follicle with a typical “lollipop” lesion [H and E], ×400. (b) Low power view of a follicle demonstrating two piercing blood vessels and three small germinal centers (arrows) [H and E], ×200. (c) Another follicle contains two germinal centers “twinning” (arrows) and a small penetrating vessel (arrowhead) [H and E], ×200. (d) This follicle demonstrates prominent onion skinning; however, the border between the mantle zone and the center is indistinct. [H and E], ×200. (e) A focus of sclerosis (arrow) is noted in this follicle [H and E], ×200. (f) Follicular dendritic cells (arrows) exhibit enlargement, coarse chromatin, and prominent nucleoli in few follicles, note the prominent onion skinning. Another example is in the inset [H and E], ×400 (g) The sinuses are patent and show dissemination of small lymphocytes (arrows), a common feature in low-grade B-cell lymphomas. Note the penetrating vessel (arrowhead) [H and E], ×200. (h) Capsular permeation by follicles is evident in this lymph node (arrows), which is a feature of follicular lymphoma rather than Castleman disease [H and E], ×20. (i) In other areas of the lymph node, the follicles had the typical morphology of follicular lymphoma, by virtue of lacking polarization and tangible body macrophages [H and E], ×200. (j) Bone marrow trephine biopsy shows sheets of small lymphocytes around bone trabeculae (arrows), which is characteristic of follicular lymphoma [H and E], ×20. (k) The follicles are positive for PAX5, Bcl-6, and Bcl-2 immunohistochemical stains. Smooth muscle active (SMA) reveals exuberant positivity in the interfollicular areas, similar to HV-CD pattern [Hematoxylin counter stain], ×20

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The abovementioned morphologic features strongly suggest the diagnosis of HV-CD. Yet, there were clues for an otherwise diagnosis of neoplastic disease. The border between the mantle zone and the germinal center was blurred and inconspicuous, instead of being sharp as in HV-CD [Figure 1]d. The lymph node sinuses were patent and showed intraluminal dissemination of small lymphocytes [Figure 1]g. In addition, the lymph node capsule was involved by proliferating follicles [Figure 1]h. More importantly, areas of classic follicular lymphoma were evident, especially in the small follicles [Figure 1]i, which are appeared different from the lymphocyte-depleted atrophic follicles of HV-CD. All follicles were positive for Bcl2, Bcl6, CD10, CD20, and PAX5 by immunohistochemistry [Figure 1]k. Flow cytometry study showed monotypic B-cells. Overall, the neoplastic follicles qualified for grade-II follicular lymphoma, and ki-67 was positive in approximately 30% of cells. Lastly, bone marrow trephine biopsy was positive for follicular lymphoma [Figure 1]j. Thus, the patient was in stage IV disease with a score of 3 (high-risk) according to Follicular Lymphoma International Prognostic Index. Treatment was indicated, given local progressive symptoms.

Follicular lymphoma is a common non-Hodgkin lymphoma, and the histologic diagnosis is frequently straightforward. Yet, the presence of unusual morphologic variants may impose difficulty in making the correct diagnosis due to their rare incidence and resemblance to other diseases, but they generally do not affect the prognosis. Thus, pathologists must be aware of the wide spectrum of morphologic variants in order to reach the correct diagnosis. The morphologic features of HV-CD were described in some cases of HIV-related lymphadenopathy, follicular lymphoma, mantle cell lymphoma, and Hodgkin lymphoma.[1] Follicular lymphoma with features of HV-CD is a very rare variant that was first described in 1992, and until now, only 13 cases were reported in the literature including our case.[2] Although FDC dysplasia was focally present in our case, this finding was not reported in any of the previous 12 cases, which could further complicate the morphologic picture.[3] The pathogenesis is unclear but could be explained by a sequential development of follicular lymphoma in an otherwise HV-CD, or by an emergence of additional FDC mutations in follicular lymphoma that results in HV-CD changes. It is imperative to differentiate this variant from true Castleman disease, as they have different prognosis and therapy regimens. The distinction depends on careful morphologic examination of the lymph nodes with an emphasis on the points we mentioned earlier. Finally, ancillary studies help elucidate the nature of these follicles whenever the pathologist is in doubt.

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.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Sevilla-Lizcano DB, Frias-Soria CL, Ortiz-Hidalgo C. Castleman disease. Histopathological and immunohistochemical analysis of 39 cases. Gav Med Mex 2017;153:550-8.  Back to cited text no. 1
Koh J, Jeon YK. Morphologic variant of follicular lymphoma reminiscent of hyaline-vascular Castleman disease. J Pathol Transl Med 2020;54:253-7.  Back to cited text no. 2
Pina-Oviedo S, Miranda RN, Lin P, Manning JT, Medeiros LJ. Follicular lymphoma with hyaline-vascular Castleman-like features: Analysis of 6 cases and review of the literature. Hum Pathol 2017;68:136-46.  Back to cited text no. 3

Correspondence Address:
Tariq N Aladily
Department of Pathology, The University of Jordan, P. O. Box 142725, Amman 11814
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_942_20

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