Peter G. Isaacson

Reactive pulmonary lymphoid disorders

The two main reactive pulmonary lymphoid disorders are lymphoid interstitial pneumonia and follicular bronchitis/bronchiolitis, both pathological entities with a variety of aetiologies. We reviewed the morphological and immunohistochemical features of 26 cases with one or other of these two diagnoses, to explore the possibility that they represented overlapping patterns of hyperpiasia of the bronchopulmonary immune system. The polymerase chain reaction was used to determine the clonality of the infiltrates. Histologically, there was a spectrum of changes with two main components. An interstitial infiltrate of mainly T lymphocytes, plasma cells and histiocytes predominated in lymphoid interstitial pneumonia, whilst lymphoid follicles predominated around airways in follicular bronchitis/bronchiolitis. Classification of the disorder rested on which component the pathologists believed to be dominant. In two cases, histology and immunohistochemistry suggested lymphoma, and in one of these cases this diagnosis was confirmed by the polymerase chain reaction. One case of lymphoid interstitial pneumonia produced three bands. The remainder produced polyclonal patterns when samples were adequate. Clinically, there was no clear difference between patients with the two disorders, or patients with pathological features of both.

Pulmonary B‐cell non‐Hodgkin's lymphomas. The value of immunohistochemistry and gene analysis in diagnosis

We reviewed 45 pulmonary B‐cell non‐Hodgkins lymphomas to determine whether their morphology and immunohistochemical features were those of lymphomas arising from mucosa‐associated lymphoid tissue (MALT), as described in other sites. The polymerase chain reaction was used to provide further information on clonality. We found that these lymphomas infiltrate the pulmonary interstitium along bronchovascular bundles and interlobular septa, subsequently spilling out into airspaces and finally destroying the alveolar architecture of the lung. Central hyaline sclerosis and vascular infiltration were common features. All lymphomas stained CD20 positive and were accompanied by variable numbers of reactive CD3 positive T‐cells. Cytokeratin staining with CAM 5.2 was useful in identifying lymphoepithelial lesions. CD21 staining of follicular dendritic cells revealed germinal centres where they were not recognizable on H & E staining. The polymerase chain reaction was performed on paraffin tissue from 28 patients. Twenty were low grade, of which 12 showed a clonal band and eight stiowed a polyclonal smear pattern. Eight were high grade, of which one revealed a clonal band. Three produced polyclonal smear patterns and four cases were inadequate samples. In one patient who had lymphoma at a second extranodal site, identical bands were identified, evidence for ‘homing’ of lymphoid cells towards mucosal epithelium.

Lymphomatoid granulomatosis: evidence that some cases represent Epstein‐Barr virus‐associated B‐cell lymphoma

Lymphomatoid granulomatosis is currently classified as part of a spectrum of angiocentric immunoproliferative lesions. These were initially thought to be of T‐cell phenotype, but recent papers have shown that some cases are B‐cell proliferations, sometimes associated with Epstein‐Barr virus infection. We reviewed the clinicopathological features of 16 patients with pulmonary lymphomatoid granulomatosis, using immunohistochemistry to assess the phenotype of the infiltrate, the polymerase chain reaction to look for immunoglobulin heavy chain and T‐cell receptor gene rearrangements, and in‐situ‐hybridization to look for Epstein‐Barr virus infection. In seven of seven cases the atypical lymphoid population was of B‐cell phenotype, with four cases showing evidence of either monoclonality or oligoclonality. All seven cases, including those that lacked unequivocal proof of malignancy, behaved aggressively. Epstein‐Barr virus RNA was detected in four cases. We conclude that some cases of lymphomatoid granulomatosis are B‐cell lymphomas, sometimes associated with Epstein‐Barr virus infection.

Splenic marginal zone lymphoma: characterization of 7q deletion and its value in diagnosis

The diagnosis of splenic marginal zone lymphoma (SMZL) is frequently a challenge, due to its lack of specific histological features and immunophenotypic markers, and the existence of other poorly characterized splenic lymphomas defying classification. Moreover, the clinical outcome of SMZL is variable, with 30% of cases pursuing an aggressive clinical course, the prediction of which remains problematic. Thus, there is a real need for biomarkers in the diagnosis and prognostication of SMZL. To search for genetic markers, we comprehensively investigated the genomic profile, TP53 abnormalities, and immunoglobulin heavy gene (IGH) mutation in a large cohort of SMZLs. 1 Mb resolution array comparative genomic hybridization (aCGH) on 25 SMZLs identified 7q32 deletion (44%) as the most frequent copy number change, followed by gains of 3q (32%), 8q (20%), 9q34 (20%), 12q23–24 (8%), and chromosome 18 (12%), and losses of 6q (16%), 8p (12%), and 17p (8%). High‐resolution chromosome 7 tile‐path aCGH on 17 SMZLs with 7q32 deletion identified by 1 Mb aCGH or interphase FISH screening mapped the minimal common deletion to a 3 Mb region at 7q32.1–32.2. Although it is not yet possible to identify the genes targeted by the deletion, interphase FISH screening showed that the deletion was seen in SMZL (19/56 = 34%) and splenic B‐cell lymphoma/leukaemia unclassifiable (3/9 = 33%), but not in 39 cases of other splenic lymphomas including chronic lymphocytic leukaemia (n = 14), hairy cell leukaemia (4), mantle cell lymphoma (12), follicular lymphoma (6), and others. In SMZL, 7q32 deletion was inversely correlated with trisomy 18, but not associated with other copy number changes, TP53 abnormalities, or IGH mutation status. None of the genetic parameters examined showed significant and independent association with overall or event‐free survival. In conclusion, 7q32 deletion is a characteristic feature of SMZL, albeit seen in isolated cases of splenic B‐cell lymphoma/leukaemia unclassifiable, and its detection may help the differential diagnosis of splenic B‐cell lymphomas. Copyright

Another look at follicular lymphoma: Immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups

The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl‐2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B‐cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype.

Significantly different bcl‐2 expression profiles in gastric and non‐gastric primary extranodal high‐grade B‐cell lymphomas

Fifty‐five cases of primary extranodal high‐grade B‐cell non‐Hodgkins lymphoma were investigated for bcl‐2 and p53 protein expression as well as for t(14;18) translocations and p53 mutations. Phenotypic and genotypic profiles were compared between tumours of gastric (27 cases) and non‐gastric (28 cases) origin. bcl‐2 protein expression was significantly lower in gastric (11/27) than in non‐gastric (28/28) lymphomas (p<0.0001), while nuclear p53 protein expression did not differ significantly between these two groups. In the stomach, there were no significant differences in either bcl‐2 or p53 expression profiles between high‐grade lymphomas with (n=14) and without (n=13) evidence of a low‐grade component of MALT type. However, secondary high‐grade lymphomas showed a significant down‐regulation of bcl‐2 protein (p<0.0001) and, conversely, an up‐regulation of p53 protein (p<0.0001) as compared with their low‐grade tumour components. In extranodal high‐grade B‐cell lymphomas, bcl‐2 protein expression was not associated with t(14;18) translocation. Only one gastric lymphoma had a p53 point mutation with potential alteration of the amino acid sequence. These findings indicate that primary gastric high‐grade B‐cell lymphomas are immunohistologically distinct from primary extranodal high‐grade B‐cell lymphomas of an origin other than in the stomach. Copyright

Primary lymphoma-like lesions of the uterine cervix; sheep in wolves' clothing.

The authors thank all the participating centres of the French Society of Haematology: CHU Bicêtre, Kremlin Bicêtre (O. Lambotte, T. Boutekedjiret); CHU de Brest (C. Berthou, G. Guillerm, M.T. Blouch); CHU de Limoges (D. Bordessoule, T. Mohamed, N. Gachard, M Donnard, A. Julia, M.P. Chaury); CHU de Nice (E. Rosenthal, F. Sanderson, A. RosenthalAllieri); CHU de Rouen (F. Jardin, J.Y. Borg, P. Chamouni); CHU Hôtel Dieu, Paris (A. Vekhoff); CHU Necker-Enfants Malades, Paris (B. Deau-Fischer, F. Monge); Centre Hospitalier de Mulhouse (B. Drenoud); Hôpital Gilles de Corbeil, Corbeil-Essonnes (C. Salanoubat, I. Lemaire).

Composite primary cutaneous peripheral T-cell lymphoma and Epstein–Barr virus-positive large B-cell lymphoma

Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital and Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Department of Dermatology, Kaohsiung Medical University Hospital, College of Medicine and Center of Excellence of Environmental Medicine, Kaohsiung Medical University, and Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, Department of Histopathology, University College London Hospital, London, UK, and Department of Pathology, Chi-Mei Medical Center, Tainan and Taipei Medical University, Taipei, Taiwan

A rare case of gastric MALT lymphoma resistant to multiple treatment regimens.

In general, patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) run an indolent clinical course and respond favourably to treatment. For example, ∼70% of gastric MALT lymphomas are cured by Helicobacter pylori eradication alone. The remaining cases, which commonly carry t(11;18)(q21;q21)/ API2-MALT1 or t(1;14)(p22;q32)/ BCL10-IGH and do not respond to H pylori eradication, can be effectively treated by radiotherapy or chemotherapy with and without rituximab. Here, we report a case of gastric MALT lymphoma, which showed an aggressive clinical course and resisted multiple regimens of chemotherapy plus rituximab.nnThe patient was in mid-50s and presented with night sweats, weight loss, left pleural effusion, erythema nodosum and a chest wall mass. Full blood count was normal with the exception of a slightly reduced haemoglobin level (9.4u2005g/dl). Lactate dehydrogenase was raised (670u2005units/l). Endoscopy showed gastric mucosa thickening. Biopsies of the gastric body and antral mucosa displayed a heavy infiltration by small lymphocytes with irregularly shaped nuclei and scanty cytoplasm (figure 1A). These lymphocytes invade gastric glands and form extensive …