Benign Lymphoid Aggregates Research Articles

Colonoscopic red ring sign due to chronic lymphocytic leukemia

The “red ring sign” is a recently described colonoscopic appearance of prominent lymphoid aggregates in the colonic mucosa. 1 Bharadhwaj G Triadafilopoulos G Endoscopic appearances of colonic lymphoid nodules: new faces of an old histopathologic entity. Am J Gastroenterol. 1995; 90: 946-950 PubMed Google Scholar , 2 Kimura M Miki K Ichinose M Hoshino E Sano J Kawamura N et al. Red ring sign—a new endoscopic finding of inflammatory bowel disease. Gastroenterology. 1990; 98 ([abstract]): A181 Google Scholar , 3 Smith MB Blackstone MO Colonic lymphoid nodules: another cause of the red ring sign [letter]. Gastrointest Endosc. 1991; 37: 206-207 Abstract Full Text PDF PubMed Scopus (5) Google Scholar , 4 Fleshner PR Ackroyd FW Shellito PC. The freckle sign—a new endoscopic feature of the cecum. Dis Colon Rectum. 1990; 33: 836-839 Crossref PubMed Scopus (4) Google Scholar , 5 Straub RF Wilcox CM Schwartz DA Variable endoscopic appearance of colonic lymphoid tissue. J Clin Gastroenterol. 1994; 19: 158-165 Crossref PubMed Scopus (5) Google Scholar , 6 Wilcox CM Anorectum. in: Atlas of clinical gastrointestinal endoscopy. W.B. Saunders, Philadelphia1995: 289-290 Google Scholar It consists of a circular red ring 2 to 3 mm in diameter surrounding a pale, slightly raised, 1 mm central area. The pale central area is a well-circumscribed lymphoid nodule, and the red ring may be due to hyperemia in the surrounding mucosal blood vessels. 2 Kimura M Miki K Ichinose M Hoshino E Sano J Kawamura N et al. Red ring sign—a new endoscopic finding of inflammatory bowel disease. Gastroenterology. 1990; 98 ([abstract]): A181 Google Scholar , 3 Smith MB Blackstone MO Colonic lymphoid nodules: another cause of the red ring sign [letter]. Gastrointest Endosc. 1991; 37: 206-207 Abstract Full Text PDF PubMed Scopus (5) Google Scholar , 4 Fleshner PR Ackroyd FW Shellito PC. The freckle sign—a new endoscopic feature of the cecum. Dis Colon Rectum. 1990; 33: 836-839 Crossref PubMed Scopus (4) Google Scholar , 5 Straub RF Wilcox CM Schwartz DA Variable endoscopic appearance of colonic lymphoid tissue. J Clin Gastroenterol. 1994; 19: 158-165 Crossref PubMed Scopus (5) Google Scholar It has been suggested that the colonoscopic red ring appearance is highly specific for underlying benign lymphoid aggregates. 1 Bharadhwaj G Triadafilopoulos G Endoscopic appearances of colonic lymphoid nodules: new faces of an old histopathologic entity. Am J Gastroenterol. 1995; 90: 946-950 PubMed Google Scholar We report a case in which the colonoscopic red ring sign was due to colonic mucosal infiltration by neoplastic lymphocytes in B-cell chronic lymphocytic leukemia (CLL).

Three-dimensional reconstruction of benign lymphoid aggregates in bone marrow trephines.

Distinguishing between deposits of low-grade non-Hodgkin's lymphoma and benign lymphoid aggregates in bone marrow trephine sections is a recognized problem in haematopathology. To test the hypothesis that benign lymphoid aggregates do not make contact with a trabecular surface, three-dimensional models were constructed of five serially sectioned bone marrow trephines, containing a total of 19 lymphoid aggregates known to be benign. The computer-generated images showed that benign lymphoid aggregates were located in the central marrow space and did not become paratrabecular. This suggests that a paratrabecular location may help in some cases to distinguish deposits of low-grade non-Hodgkin's lymphoma from benign lymphoid aggregates.

Follicular dendritic cells in bone marrow lymphoproliferative diseases: an immunohistochemical study including a new paraffin‐resistant monoclonal antibody, DR53

Two-hundred and twenty-one bone marrow biopsies with lymphoid infiltrates were studied histologically and immunohistochemically, to assess the incidence and the pattern of follicular dendritic cells. Three monoclonal antibodies selective for follicular dendritic cells were used: CD21, CD35 and DR53, all reactive on paraffin-embedded material. Follicular dendritic cells were present in two of 38 benign lymphoid aggregates, 92 of 134 low grade B-cell lymphomas (45 of 62 lymphocytic, 16 of 27 lymphoplasmacytoid, 0 of six hairy cell leukaemias, five of six centrocytic, 19 of 21 centroblastic-centrocytic, seven of 12 low grade NOS), one of 23 high grade B-cell lymphomas, 0 of 10 T-cell lymphomas, 0 of three Hodgkin's disease and four of 13 suspicious infiltrates. Follicular dendritic cells were found in lymphomatous involvement with nodular, patchy and massive growth pattern, but not in interstitial ones. They formed follicle-like networks, whose number and size were directly correlated to the tumour mass. The origin and frequency distribution of follicular dendritic cells in bone marrow biopsy lymphomas is discussed and the diagnostic relevance of follicular dendritic cell immunostaining in routine bone marrow biopsy lymphoid infiltrates is assessed.

Discordant morphologic features in bone marrow involvement by malignant lymphomas: use of gene rearrangement patterns for diagnosis.

Discordant morphology between lymph node or extra-nodal site and bone marrow (BM) involvement by non-Hodgkin's malignant lymphoma (NHL) is a common occurrence, causing diagnostic difficulties. Additional diagnostic problems are posed by lymphoid aggregates commonly found in the BM of elderly patients, the age group with the highest incidence of lymphoma. Morphologic features are used to distinguish between benign and malignant lesions but no feature is diagnostic and exceptions are numerous. Immunophenotyping is helpful for detecting B cell monoclonality, but it cannot detect T cell monoclonality. Unique B and T cell gene rearrangement patterns, the molecular "signature" of the lymphoma, can be used to detect monoclonal lymphoid populations. Finding the same rearrangement pattern in the BM as in the primary mass is proof of BM involvement by the same clone of malignant cells. We used B/T and Bcl-2 gene rearrangements to help diagnose cases with discordant morphology between primary site and BM. One hundred and seventy-five specimens, obtained from patients undergoing staging or restaging for NHL, were analyzed for B/T cell and Bcl-2 gene rearrangements by multiple restriction endonuclease digestion and Southern hybridization with 32P labeled JH, JK, CT beta, and Bcl-2 probes. Forty-two specimens (24%) from 24 patients showed discordant morphology: of 13 specimens with atypical lymphoid aggregates, only one had B cell gene rearrangement; of 15 specimens with morphologically benign lymphoid aggregates, one demonstrated B cell gene rearrangement; and of 14 specimens positive for NHL with different morphology than the lymph node, 13 were positive for B cell gene rearrangements. Molecular analysis can aid in the diagnosis of NHL, can establish a "baseline" for detection of recurrence, and is useful in monitoring therapy. These data suggest that it is also a tool for the pathologist in cases of discordant morphology between the primary tumor and BM, and should be strongly considered for each site.

Primary myelodysplastic syndromes: diagnostic and prognostic significance of immunohistochemical assessment of bone marrow biopsies

Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French-American-British [FAB] types: refractory anemia [RA] = 21; RA with ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB criteria were not applicable) was analyzed for bone marrow histologic and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and reticulin stains were used for morphologic assessment. To identify the cell lineage precisely, chloroacetate esterase staining and an indirect immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin- fixed paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment permitted accurate identification of dysplastic features such as mononuclear and binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone marrow histologic and immunohistochemical features observed were heterogeneity of immunohistochemical staining in various cell lineages, megakaryocytic emperipolesis, alteration of bone marrow microarchitecture, intravascular clusters of hematopoietic cells, and the types of benign lymphoid aggregates. The nature of abnormally localized immature precursors (ALIP) was discerned. Three types of clusters of immature cells were found that were difficult to distinguish on Giemsa and H&E morphology, these were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic and monocytic aggregates (n = 32). The bone marrow histologic and immunohistologic patterns permitted the identification of four groups of clinical relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases in group 2 showing the worst prognosis with early death due to increased propensity to leukemic transformation and cytopenia-related complications (P less than .0001). We conclude that immunohistochemistry is feasible on routinely processed BMB and the information obtained is of diagnostic and prognostic importance in P- MDS. The phenotype of ALIP varies with the morphologic and histologic subtypes of MDS and the term should be reserved for cases in whom the clusters in the intertrabecular region are of myeloid (granulocytic and monocytic) lineage on immunohistochemistry.

Primary Myelodysplastic Syndromes: Diagnostic and Prognostic Significance of Immunohistochemical Assessment of Bone Marrow Biopsies

Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French-American-British [FAB] types: refractory anemia [RA] = 21; RA with ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB criteria were not applicable) was analyzed for bone marrow histologic and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and reticulin stains were used for morphologic assessment. To identify the cell lineage precisely, chloroacetate esterase staining and an indirect immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin-fixed paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment permitted accurate identification of dysplastic features such as mononuclear and binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone marrow histologic and immunohistochemical features observed were heterogeneity of immunohistochemical staining in various cell lineages, megakaryocytic emperipolesis, alteration of bone marrow microarchitecture, intravascular clusters of hematopoietic cells, and the types of benign lymphoid aggregates. The nature of abnormally localized immature precursors (ALIP) was discerned. Three types of clusters of immature cells were found that were difficult to distinguish on Giemsa and H&E morphology, these were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic and monocytic aggregates (n = 32). The bone marrow histologic and immunohistologic patterns permitted the identification of four groups of clinical relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases in group 2 showing the worst prognosis with early death due to increased propensity to leukemic transformation and cytopenia-related complications (P less than .0001). We conclude that immunohistochemistry is feasible on routinely processed BMB and the information obtained is of diagnostic and prognostic importance in P-MDS. The phenotype of ALIP varies with the morphologic and histologic subtypes of MDS and the term should be reserved for cases in whom the clusters in the intertrabecular region are of myeloid (granulocytic and monocytic) lineage on immunohistochemistry.

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.

Lymphoid aggregates in bone marrow: study of eventual outcome.

The practical importance of finding a morphologically benign lymphoid aggregate in the bone marrow of patients without known lymphoproliferative disease was assessed in 786 consecutive patients who had had 951 iliac crest bone marrow biopsies performed. Of these, 430 patients known to have lymphoproliferative disease at the time of biopsy were excluded. Of 356 patients, 86 (aggregate group) had at least one lymphoid aggregate in their biopsy specimen biopsy specimen (82 morphologically benign, three suspicious, and one malignant). Another 86 patients without aggregates (control group) were matched by age and sex. Both groups were followed up until death, or for a mean of 21.9 and 22.9 months, respectively, to assess their outcome. Eighteen (22%) of the 82 patients with morphologically benign lymphoid aggregates were later proved to have lymphoproliferative disease compared with none of the 86 control patients. Another 12 patients in the aggregate group and seven in the control group were suspected of having a lymphoproliferative disease on clinical grounds, so that altogether 30 (37%) and seven (8%), respectively, developed confirmed or suspected lymphoproliferative disease. In both cases the differences were highly significant (p less than 0.001). It is suggested that lymphoid aggregates in clinical biopsy material may not be a physiological finding and should alert pathologists or haematologists to the possibility of lymphoproliferative disease.

Benign and malignant (B cell) focal lymphoid aggregates in bone marrow trephines shown by means of an immunogold-silver technique.

A series of 36 iliac crest trephines, previously shown to contain follicular lymphoid aggregates, were examined using the immunogold-silver staining technique. This showed the presence of kappa and lambda surface immunoglobulin in paraffin sections of the specimens. In those trephines from patients known to be suffering from chronic lymphocytic leukaemia there was distinct monoclonality for expression of either kappa or lambda surface light chains on the lymphocyte cell surfaces in and usually between the lymphoid nodules. In specimens containing aggregates, which had previously been diagnosed as benign on morphological and clinical criteria, both kappa and lambda chains were expressed. A small number of trephines containing aggregates of uncertain nature were also examined; these all showed monoclonal expression of either kappa or lambda chains and subsequently proved to be clinically malignant. Dendritic reticulum cells, shown by staining for surface immunoglobulin, were observed only in benign aggregates.