Diagnosis Of Marginal Zone B-cell Lymphoma Research Articles

Deciphering the spectrum of cutaneous lymphomas expressing TFH markers

T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the “TFH-spectrum” is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL (TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD (TET2), 40% of PCTFHL (SOCS1 (20%), ARID1A (20%)) and 64% of cAITL (TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases.

Primary marginal zone B-cell lymphoma of the cavernous sinus: a case report and review of the literature

BackgroundPrimary lymphoma of the cavernous sinus is a rare form of extranodal non-Hodgkin lymphoma, of which very few cases have been reported in the published literature. This report presents the MRI findings with apparent diffusion coefficient (ADC) value in an exceedingly rare primary marginal zone B-cell lymphoma (MZBCL) of the cavernous sinus.Case presentationThe case in this study is a 59-year-old immunocompetent male patient with a 2-month history of right ptosis and blurred vision. Right third cranial nerve palsy and binocular diplopia were observed upon neurological examination. Preoperative brain CT showed an extra-axial enhancing mass lesion in the right cavernous sinus. On MRI, ipsilateral internal carotid arterial encasement was noted without causing stenosis of the vessel. Isointense signal on T1-weighted and T2-weighted images, homogeneous contrast enhancement, and diffusion restriction were also observed. The mean ADC value of the tumor is 0.64 × 10–3 mm2/s (b value = 1000 s/mm2). Subtotal resection of the tumor was performed, and improvement of clinical symptoms were observed. The pathologic diagnosis of MZBCL was established by immunohistochemical examinations.ConclusionsPrimary MZBCL of the cavernous sinus is exceedingly rare, and preoperative confirmation poses a major challenge with CT and conventional MRI only. In this case, preoperative quantitative ADC value is shown to offer valuable additional information in the diagnostic process.

Marginal-Zone Lymphoma Mimicking Adrenal Myelolipoma on Computed Tomography Scan

A 69-yr-old woman was referred for a left adrenal mass incidentally discovered at computed tomography (CT) scan that was performed for abdominal pain. Clinical examination showed no signs of corticosteroid or catecholamine excess, and hormone assays revealed no abnormality. At CT scan, the lesion appeared as a 6-cm heterogeneous mass containing low-density fat surrounded by dense tissue (Fig. 1A). The neoplasm was associated with infiltration of the left perirenal fascia evocative of an inflammatory process (Fig. 1B). The diagnosis of adrenal myelolipoma complicated by extracapsular hemorrhage was suggested (1), and surgical removal of the lesion was performed through retroperitoneoscopy. Pathology showed no adrenal neoplasm but revealed an invasion of the periadrenal fat tissue by proliferation of monomorphic small lymphocytes (Fig. 1, C and D, and Fig. 2A). Immunolabeling of the tissue (Fig. 2, B and C) allowed establishing the diagnosis of marginal-zone B-cell lymphoma (MZL). Staging procedures showed involvement of spleen and bone marrow. Considering the good prognosis of MZL, therapeutic abstention was decided. Non-Hodgkin’s adrenal lymphomas are usually diffuse extranodal large B-cell lymphomas with poor prognosis. When bilateral, destruction of the adrenals by the proliferative lymphocytic process frequently results in adrenal insufficiency (2). Very rarely, lymphomas of the adrenal areas belong to the MZL subtype, also called small B-cell lymphoma (2, 3). MZLs arise from a marginal-zone B cell present in lymph nodes and extranodal tissues and are considered as indolent malignancies (3). In the patient’s case, invasion of periadrenal fat tissue by lymphocytic proliferation mimicked the appearance of adrenal myelolipoma on CT scan, i.e. a heterogeneous mass with mature fat intermingled with dense myeloid tissue (4).

Asymptomatic bone marrow involvement in patients presenting with cutaneous marginal zone B-cell lymphoma

Conflicts of interest: none declared. Sir, Marginal zone B‐cell lymphoma (MZL) is one of the most frequent B‐cell lymphomas of the skin. In the recent WHO–EORTC classification primary cutaneous B‐cell lymphoma is defined as lymphoma involving the skin with no evidence of extracutaneous disease at the time of diagnosis.1 An MZL located to the skin can be a primary cutaneous MZL (PCMZL) or a secondary cutaneous spread of a disseminated MZL. We aimed to determine the initial presentations and outcomes for our patients presenting with a skin lesion of MZL. Patients who were registered in our dermatopathological database between January 2000 and June 2006 and for whom the diagnosis of MZL was retained were studied. Five other patients had a diagnosis of extracutaneous MZL before the onset of cutaneous lesions (not analysed in clinical results). Biopsy specimens were reviewed by two pathologists (B.B., F.B.) using criteria of the WHO–EORTC classification of cutaneous lymphoma. Polymerase chain reaction analysis of IgH gene found clonal rearrangement in 31 of 39 cases (79%).

Primary cutaneous marginal zone B-cell lymphoma: a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases.

Primary cutaneous marginal zone B-cell lymphoma (MZCL) has recently been described. Differentiation from follicular centre cell lymphomas and lymphocytomas is often difficult due to insufficient experience and a lack of large series of patients. To characterize primary cutaneous MZCL better, we report clinical, histopathological, immunophenotypic and molecular genetics features in a series of 22 patients. All patients were treated and followed up at the same institution. Diagnosis of MZCL was based on the World Health Organization classification criteria. All samples were routinely tested with a wide panel of monoclonal antibodies. DNA was extracted from every sample following standard methods. IgH rearrangement and t(14;18)(q32;q21) studies were performed in all samples. Twenty-two patients (20 men, two women; mean age 50 years, range 24-77) were included. The mean follow-up was 43 months. Seventy per cent of patients presented with characteristic skin lesions on the trunk or extremities, consisting of deep red to violaceous infiltrated plaques, nodules or tumours frequently surrounded by diffuse or annular erythema. Four patients presented with lesions on the head and neck area. Two patients had disseminated skin lesions. The main histopathological features were non-epidermotropic, dense lymphocytic infiltrates mainly distributed in a nodular pattern. Adnexal involvement was usually present, with eventual formation of lymphoepithelial complexes. Cytologically, the infiltrate was polymorphous with marginal zone B cells and B-monocytoid cells. Blastoid CD30+ cells were often observed. Colonized reactive germinal centres and lymphoplasmocytoid differentiation were frequently present. Neoplastic cells were CD20+, CD79a+, CD5- and CD10-. Monotypic expression of light chains was observed in 18 cases (13 kappa; five lambda). Clonal IgH rearrangements were detected in 14 cases. The bcl-2 mutation t(14;18)(q32;q21) was demonstrated in two cases. Most patients were treated with local radiotherapy. Complete response rate with this approach was 100%. Six patients (27%) had skin recurrences from 6 months to 8 years after first treatment. Five patients (23%) had extracutaneous involvement. Two of them had a large cell transformation and one died of lymphoma. Three of four patients with head and neck presentation developed extracutaneous disease. MZCL appears to be a well recognizable entity, clinically, histologically and immunophenotypically. Although prognosis is generally good, the disease has potential for skin as well as extracutaneous recurrences. Large cell transformation and head and neck presentation may be associated with a worse prognosis.