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Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 222-226
Primary cutaneous marginal zone lymphoma (immunocytoma like) with lymphoepithelioid or Lennert's lymphoma like involvement of nodes

1 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India
2 Department of Molecular Pathology, Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, India
3 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai; Department of Molecular Pathology, Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, India

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Date of Web Publication3-Jul-2012


Primary cutaneous marginal zone lymphomas (PCMZL) have a wide range of morphology from tumors with monocytoid B cells to those composed entirely of plasma cells and the T-cell rich variants. We report a 60-year-old male with a PCMZL rich in plasma cells of the foot with a lymphoepithelioid-like pattern of dissemination to the lymph nodes posing problems in the diagnosis. The patient had a lesion on the dorsum of the foot which histologically revealed dense perivascular collections of lymphoid cells and plasma cells amidst fibrous tissue. Though the plasma cells did show light chain restriction, CD20 and CD3 did not reveal an overwhelming B/T-cell population and hence a diagnosis of a reactive process was offered. Subsequently the patient developed inguinal nodes with diffuse loss of architecture and replacement by epithelioid histiocytes and reactive T cells with few large B cells (lymphoepithelioid-like pattern). On pathology review it was realized that the two lesions may be related and clonality studies were asked for. The skin lesion showed clonally rearranged IgH receptor while the T-cell receptor rearrangement was negative. The patient developed disseminated disease and received six cycles of chemotherapy with partial response and 6 years after the initial presentation was alive with nonprogressive disease. Thus, the polymorphous background in PCMZL is evolving and an immunocytoma-like tumor can show a T-cell rich or Lennert's like growth pattern of spread and early recognition these odd patterns may aid in appropriate management of patients.

Keywords: Immunocytoma, lymphoepithelioid lymphoma, lymphoma, primary cutaneous marginal zone lymphoma

How to cite this article:
Shet T, Basak R, Epari S. Primary cutaneous marginal zone lymphoma (immunocytoma like) with lymphoepithelioid or Lennert's lymphoma like involvement of nodes. Indian J Pathol Microbiol 2012;55:222-6

How to cite this URL:
Shet T, Basak R, Epari S. Primary cutaneous marginal zone lymphoma (immunocytoma like) with lymphoepithelioid or Lennert's lymphoma like involvement of nodes. Indian J Pathol Microbiol [serial online] 2012 [cited 2022 May 20];55:222-6. Available from: https://www.ijpmonline.org/text.asp?2012/55/2/222/97882

   Introduction Top

Marginal zone lymphomas at most sites are a diagnosis of exclusion as they are morphologically extremely heterogeneous with polymorphous population of marginal zone (centrocyte-like) cells, lymphoplasmacytoid cells, and plasma cells with variable prominence of one cell or other. [1] Generally a dominance of B cells in a cutaneous infiltrate points toward a possibility of B-cell lymphoma. However primary cutaneous marginal zone lymphomas (PCMZL) are notorious and may show tumors with dominance of plasma cells mimicking plasmacytoma and tumors with T-cell rich areas mimicking primary cutaneous T-cell lymphomas-like mycosis fungoides or even reactive processes. [1],[2] All of these entities though indolent have different management options and hence it is crucial to recognize this odd spectrum of PCMZL.

We describe an immunocytoma-like PCMZL which was misdiagnosed as a reactive lesion at the onset and which went on to progress into a systemic disease with lymphoepithelioid or Lennert's T-cell lymphoma-like growth pattern.

   Case Report Top

A 60-year-old man complained of nonpainful nodular swelling on the dorsum of the left foot 5.5 × 3 × 1.5 cm which waxed and waned over last 2 years. The patient was manual laborer, nondiabetic, and gave no other significant clinical history. On examination the lesion was hard to feel and the skin over the swelling was puckered, but not ulcerated. The patient was also found to have a 1 cm sized palpable inguinal node on the same side. Subsequently the foot lesion was completely excised due to inconvenience in walking and under the impression of a chronic fibrosed abscess by a general surgeon in 2004. The inguinal node was not excised. Following the diagnosis of a nonspecific inflammatory pathology, the patient was given a course of antibiotics and kept on close follow-up. A year later the patient observed a progressive increase in the inguinal node but as the skin scar was healthy; he was kept under observation till the node became 3 cm in size and hence was excised in 2008. The histologic impression on this node biopsy was peripheral T-cell lymphoma of Lennert's type and patient was referred to our institute for therapy.

In the lymphoma clinic it was realized that both the lesions might be linked and a review of previous histology was asked for. After clonality studies and literature review the diagnosis on the foot lesion was revised to primary cutaneous marginal zone lymphoma plasma cell rich with Lennert's like spread to nodes and patient was further investigated. A positron emission tomography (PET) scan with computerized tomography (CT) revealed multiple nodes in abdomen and bilateral axillary nodes ranging in size from 1 cm to 2 cm. As he was asymptomatic he was further followed up till he developed multiple mediastinal and cervical lymph nodes with weight loss and loss of appetite in late 2009. Bone marrow examination remained unremarkable all throughout the course of the disease. He was given two cycles of CVP (cyclophosphamide, vincristine, prednisone) followed by four cycles of CHOP (cyclophosphamide, adriamycin, oncovin, prednisolone) with symptomatic improvement and 70% reduction in lymphadenopathy. Rituximab was not given, as CD20-positive cells within the nodes were minimal. He subsequently received palliative radiotherapy and had static nonprogressive disease till March 2011 (8 years after initial presentation and 6 years after foot lesion excision).

   Histologic Findings Top

Primary Skin Lesion

The specimen of the foot lesion was 5.5 × 3 × 1.5 cm and showed a skin covered bosselated lesion with firm white cut surface. The excision specimen histology revealed dense fibrosis with nodules of plasma cells and lymphoid cells centered around the blood vessels. The lymphocytes were mature and admixed with scattered immunoblasts [Figure 1]a and b. At places the plasma cells formed large nodules with frequently binucleate cells [Figure 2]. Immunohistochemistry was performed using the ABC technique. The lymphoid cells showed mature T cells admixed with CD20 and CD30 positive immunoblasts [Figure 3]a and b. Overall the CD4:CD8 ratio was 1:2. The plasma cell light chain restriction studies were ordered much later during the review and a lambda chain restriction was noted [Figure 4]. CD56, EBER-ISH (Novocastra kit), HHV8-LNA1, Granzyme B, and ALK 1 were negative.
Figure 1: (a) The foot lesion on microscopy revealed dense fibrosis with nodules (Hematoxylin and eosin, × 200). (b) These nodules revealed small mature lymphoid cells, plasma cells, and immunoblasts (arrow)(Hematoxylin and eosin, × 400)

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Figure 2: Areas with nodules of plasma cells with frequent binucleate forms (Hematoxylin and eosin, × 200)

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Figure 3: (a) On immunohistochemistry CD 3 stains reactive mature T lymphocytes (ABC, × 100). (b) CD20 stained scattered larger B cells (ABC, × 400)

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Figure 4: Lambda restriction within the plasma cells in the lesion (ABC, ×400)

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Lymph Node Histology

The inguinal nodes were 2 cm in size and had a fleshy cut surface. On microscopy they revealed a diffuse loss of architecture with diffuse replacement of node by small T cells and epithelioid histiocytes in a lymphoepithelioid lymphoma (Lennert's like) pattern with delicate fibrous bands [Figure 5]a and b. Two-thirds of cells in node stained with CD3 while CD20 stained clusters of both small and larger immunoblast-like cells [Figure 6]a and b. The epithelioid histiocytes stained with CD68/CD163. No plasma cells were observed within this lesion and hence Kappa and lambda were not done. However as opposed to a Lennert's lymphomas high endothelial venules were not seen. The CD4:CD8 ratio was similar 1:2. MIB1 was uniformly low at 15%.
Figure 5: (a) Inguinal node histology reveals total replacement by epithelioid histiocytes, mature lymphocytes arranged in a Lennert's/lymphoepithelioid-like pattern (Hematoxylin and eosin, ×100). (b) Higher power shows admixture of smaller T cells, epithelioid histiocytes, and an occasional immunoblasts separated by delicate bands of fi brosis (Hematoxylin and eosin, ×400)

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Figure 6: Immunohistochemistry on lymph node revealed (a) predominance of CD3 positive T cells (ABC, ×100), (b) while B cells were in small clusters on CD20 staining (ABC, ×200)

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Molecular Studies

IgH and T-cell receptor rearrangement studies were asked for during the review and were done on paraffin-embedded material using the following method:

DNA extraction -- Total cellular DNA from tissue biopsy samples was extracted from 10 formalin fixed paraffin-embedded sections (FFPE) (each 10 μm thick) using a QIAamp DNA Mini kit from Qiagen. Amplification of a fragment of the housekeeping gene β-actin was used as a positive control for successful amplification of the extracted DNA. All standard precautions were taken to guard against cross-contamination of amplified DNA. Polyclonal DNA (reactive lymphoid tissues) and negative (sterile water [blank]) controls were systematically included.

Primer design --
Analysis of IgH gene rearrangements was performed by seminested PCR (sn-PCR) according to the method of Trainor et al.[3] using FRIII-VH-specific primer amplifications. The primers used for amplifying the IgH gene were: FR3A- 5΄-ACA CGG C(C/T)(G/C) TGT ATT ACT GT-3΄ for the 3΄ end of the V region; and LJH-5΄-TGA GGA GAC GGT GAC C-3΄ and VLJH-5΄-GTG ACC AGG GTN CCT TGG CCC CAG-3- for the 3΄ end of the J region. The demonstration of TcR-γ gene rearrangements was performed by using a multiplex PCR with a set of four primers primers. [4],[5] These primers were: VγI cons: 5΄-CTG GTA CCT ACA CCA GGA GGG GAA-3, Jγ 2S2: 5΄-CCT GTG ACA ACA AGT GTT GT-3΄, JP: 5΄-TTG TTC CGG GAC CAA ATA CC-3΄, JP1/2: 5΄-CCA GGT GAA GTT ACT ATG AG-3΄

PCR conditions -- The PCR was performed using 1 × Master mix (Qiagen), 10 pico moles of each primer, and 100--200 ng of template DNA. For amplification of the TCRγ gene, mixed primers were used and a single round of PCR (40 cycles of 94°C for 1 minute, 55°C for 1 minute, and 72°C for 1 minute) was performed. For amplification of the IgH genes, a seminested PCR was performed: a first round of 30 cycles with primers LJH and FR3A, followed by a 1:100 dilution, and then a second round of 25 cycles with primers VLJH and FR3A. Each PCR round was preceded by a 5-minute denaturation at 94°C and was followed by a final extension of 20 minutes at 72°C. Five microliters of the reaction product was electrophoresed through 2% agarose or 6% polyacrylamide in the TBE buffer (89 mmol/l Tris, 89 mmol/l boric acid, 2 mmol/l EDTA), and examined under short-wavelength UV light after ethidium bromide staining.

   Results Top

In this case, PCR with the IgH primers resulted in one discrete band of amplified material, 100--120 bp in size. The amplification was observed with FR3a/JH primer pairs [Figure 7]. Conversely, PCR with the TCR primers was negative. IgH receptor rearrangements and TCR on inguinal node could not be done as the material was depleted.
Figure 7: Gel electrophoresis image to shows a band in the 100--120 bp (dotted circle) using FR3 primers indicating an IgH receptor rearrangement

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   Discussion Top

PCMZL with extensive plasmacytic differentiation have been labeled as cutaneous primary immunocytoma but in the present WHO 2008 classification they have been clubbed with PCMZL as essentially both represent the same disease entity with similar management options. [1] Differentiating plasma cell-rich PCMZL from plasmacytomas and reactive inflammation is crucial given the different management options [6],[7] and misdiagnosis is common as was also noted in the case we report. In retrospect the presence of a fair number of mature lymphoid cells with arrangement around blood vessels, in the absence of an infective etiology, was a pointer toward a neoplastic process like PCMZL. The presence of any lymphoid follicles, B cells, and follicular dendritic cells also tends to exclude plasmacytoma and favors a PCMZL in any plasma cell-rich infiltrate in skin. [7] Finally the presence of IgH gene rearrangement also helps in differentiating cutaneous plasmacytomas from PCMZL (immunocytoma like) and in confirming the clonal nature of the proliferation. It is essential to know that this excess plasma cell differentiation fluctuates in a PCMZL and the subsequent recurrences may be totally devoid of plasma cells. [2]

PCMZL admixed with large population of T cells or T-cell rich PCMZL have been recently reported and stand a chance of being misdiagnosed as reactive processes or mycosis fungoides. [2] As with the plasma cell-rich variants of PCMZL, polymorphous clusters of scattered immunoblasts, lymphoplasmacytoid cells, and plasma cells at the periphery of the T-cell rich infiltrates are clues to recognize them as B-cell lymphomas. [8] Also there was no epidermotrophism seen in mycosis fungoides and clonality studies further help in differentiating a T-cell process from a B-cell process.

Dr. Lennert's group described nodal lymphoplasmacytoid immunocytoma with high content of epithelioid cells that closely mimicked T-cell lymphomas especially the lymphoepithelioid or Lennert's subtype and Hodgkin's lymphoma. [9] Through evolving definitions in classification of non-Hodgkin's lymphoma it is likely that this group would be reclassified as the T-cell and histiocytic rich variants of nodal marginal zone lymphomas. Among the 39 cases discussed in that paper, immunoblasts and plasmablasts were seen in large amounts in 79% of cases and typical RS cells were observed in 2--6% of tumors which were otherwise composed of sheets of epithelioid histiocytes. [9] A similar pattern was observed in the node in the case we discuss and was misdiagnosed as peripheral T-cell lymphoma (PTCL) Lennert's type. A good histological clue was that high endothelial venules which are usually seen in PTCL were absent. It is only when we put the clinical history in appropriate context the whole case evolved. Though we could not confirm clonality on node due to depletion of tissue, clinically the patient had disease progression starting from the inguinal region onward and it was likely that the nodal disease was indeed due to dissemination of the PCMZL. Such lymphoepithelioid pattern has been described in PCMZL of the skin but to the best of our knowledge there is no literature report of PCMZL plasma cell-rich variant producing a lymphoepithelioid-like pattern of spread within the lymph nodes.

The waxing and waning of the skin lesion made us first think of lymphomatoid papulosis given the CD30-positive cells. But the CD30 expression was seen with CD20 expression attesting to their B-cell nature. The presence of IgH rearrangement further indicated a B-cell lymphoma. Waxing and waning is known in PCMZL which may also undergo spontaneous resolution at least during the first months of the disease. [1]

The recurrence rate in PCMZL ranges from 30% to 70% and appears independent of the treatment modality used. [10] Recurrence rates in the T-cell rich variants of PCMZL are similar to these rates, with relapsing disease present in 40% of patients in the T-cell rich group, indicating that the T-cell rich variant of PCMZL has no prognostic implications. Extracutaneous spread of PCMZL is noted in 8--17% of patients. [2],[10] While multiagent chemotherapy is rarely used for PCMZL, CHOP regimen (cyclophosphamide, adriamycin, oncovin, prednisone) lead to 85% complete remission in published studies with 57% relapse rates and should be restricted to patients with more aggressive disease such as the presence of B symptoms, high LDH level and progression or transformation. [10] The patient we discuss had dissemination with an refractory but indolent disease; whether the transformation to the lymphoepithelioid pattern had a role to play is not clear.

To conclude PCMZL is a heterogeneous disease with T-cell rich and plasma cell-rich variants but the background population of the reactive cells is constantly evolving and hence it is not unusual that a plasma cell rich variant of PCMZL showed a lymphoepithelioid pattern of spread of dissemination to the regional nodes. Awareness of such cases may help institute therapy earlier and probably alter the course of disease.

   References Top

1.Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, et al. EORTC classification for primary cutaneous lymphomas: A proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997;90:354-71.  Back to cited text no. 1
2.Geyer JT, Ferry JA, Longtine JA, Flotte TJ, Harris NL, Zukerberg LR. Characteristics of cutaneous marginal zone lymphomas with marked plasmacytic differentiation and a T cell-rich background. Am J Clin Pathol 2010;133:59-69.  Back to cited text no. 2
3.Trainor KJ, Brisco MJ, Wan JH, Neoh S, Grist S, Morley AA. Gene rearrangement in B- and T-lymphoproliferative disease detected by the polymerase chain reaction. Blood 1991;78:192-6.  Back to cited text no. 3
4.Al Saati T, Galoin S, Gravel S, Lamant L, Roda D, Chittal S, et al. IgH and TcR-g gene rearrangements in Hodgkin's disease by PCR demonstrate lack of correlation between genotype, phenotype and Epstein-Barr virus status. J Pathol 1997;181:387-93.  Back to cited text no. 4
5.Macintyre EA, d'Auriol L, Duparc N, Leverger G, Galibert F, Sigaux F. Use of oligonucleotide probes directed against T cell antigen receptor gamma delta variable-(diversity)-joining junctional sequences as a general method for detecting minimal residual disease in acute lymphoblastic leukemias. J Clin Invest 1990;86:2125-35.  Back to cited text no. 5
6.Rijlaarsdam JU, van der Putte SC, Berti E, Kerl H, Rieger E, Toonstra J, et al. Cutaneous immunocytomas: A clinicopathologic study of 26 cases. Histopathology 1993;23:117-25.  Back to cited text no. 6
7.Magro CM, Porcu P, Ahmad N, Klinger D, Crowson AN, Nuovo G. Cutaneous immunocytoma: A clinical, histologic, and phenotypic study of 11 cases. Appl Immunohistochem Mol Morphol 2004;12:216-24.  Back to cited text no. 7
8.Cerroni L, Signoretti S, Höfler G, Annessi G, Pütz B, Lackinger E, et al. Primary cutaneous marginal zone B-cell lymphoma: A recently described entity of low-grade malignant cutaneous B-cell lymphoma. Am J Surg Pathol 1997;21:1307-15.  Back to cited text no. 8
9.Patsouris E, Noël H, Lennert K. Lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells. Histologic and immunohistochemical findings. Am J Surg Pathol 1990;14:660-70.  Back to cited text no. 9
10.Dalle S, Thomas L, Balme B, Dumontet C, Thieblemont C. Primary cutaneous marginal zone lymphoma. Crit Rev Oncol Hematol 2010;74:156-62.  Back to cited text no. 10

Correspondence Address:
Tanuja Shet
Professor and Pathologist, Department of Pathology, 8th Floor, Annex building, Tata Memorial Hospital, Parel, Mumbai - 400 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.97882

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