VII.C.001

Burkitt lymphoma. Lymph node biopsy. Low power. H&E stain. Characteristic sheets of lymphoblasts with interspersed macrophages, the latter giving it a “starry sky” appearance.

VII.C.002

Burkitt lymphoma. Lymph node biopsy. Ki-67 nuclear stain giving a red-brown color to the lymphoblasts and confirming high proliferative rate of >90% of cells. Ki-67 is cell cycle regulatory protein.

VII.C.003

Burkitt lymphoma. Lymph node biopsy. Wright’s Giemsa stain of air-dried lymph node touch preparation shows blast-like large lymphoid cells with prominent nucleoli and frequent cytoplasmic vacuoles. Mitotic figures. Tissue equivalent of acute lymphoblastic leukemia of Burkitt type.

VII.C.004

Burkitt lymphoma. Lymph node biopsy. Low power view. Note areas of clearing that impart the so-called “starry sky” appearance. These areas represent tingible-body macrophages within the tumor that are recruited to phagocytize cellular debris. A similar appearance may also be seen in other lymphomas that have a high proliferative rate.

VII.C.005

Burkitt lymphoma. Lymph node. Biopsy. Higher power view. Individual tumor cells have a high nuclear: cytoplasmic ratio, round nuclear contours, and small, barely perceptible nucleoli (sometimes called “inconspicuous” nucleoli). These overall features are often referred to as a “small non-cleaved” cell or “small transformed” cell cytology.

VII.C.006

Burkitt lymphoma. Lymph node biopsy. (A) Lower power view showing diffuse replacement of nodal tissue with Burkitt lymphoblasts with classical interspersed macrophages presenting a starry sky appearance. (B) Higher power view. Burkitt lymphoblasts with prominent nucleoli. Interspersed macrophages with ingested cellular debris. Relative increase in mitotic figures.

VII.C.007

Burkitt lymphoma. Lymph node biopsy. (A) Lower power view showing diffuse replacement of nodal tissue with Burkitt lymphoblasts with classical interspersed macrophages presenting a starry sky appearance. (B) Higher power view. Burkitt lymphoblasts with prominent nucleoli. Interspersed macrophages with ingested cellular debris.

VII.C.008

Cryoglobulinemia. Blood films. (A) Gray precipitates in blood taken from a finger stick (acral cooling). Hypersegmented neutrophil. (B) Gray precipitates in blood taken from finger stick (acral cooling). Small platelet aggregate.

VII.C.009

Cryocrystalglobulinemia. Blood films. Patient with circulating immunoglobulin that crystallized at room temperature. (A) Higher power image of blood film prepared at room temperature with precipitated crystals, ranging from about 5 to 60μM in length. (B) Lower power blood film displaying precipitated crystals. No crystals were evident at 37^oC. The white count fluctuated unpredictably based on the temperature of blood during white cell counting. At temperatures closer to room temperature the crystals were being counted as white cells by the electronic particle counter. This type of phenomenon is less of a problem with more modern analyzers that rely on light scatter to identify and enumerate blood cells than on older analyzers that used electrical impedance (Coulter principle) to detect blood cells.

VII.C.010

Cryocrystalglobulinemia. Blood films. Patient with circulating immunoglobulin that crystallized at room temperature. (A) Blood film prepared at room temperature with precipitated crystals. (B) Precipitated crystals. Note very long crystals approaching 100μM in length. No crystals were evident at 37^oC. The white count fluctuated unpredictably based on the temperature of blood during white cell counting. At temperatures closer to room temperature the crystals were being counted as white cells by the electronic particle counter. This phenomenon is less of a problem with more modern analyzers that rely on light scatter to identify and enumerate blood cells than on older analyzers that used electrical impedance (Coulter principle) to detect blood cells.

VII.C.011

Cryocrystalglobulinemia. Blood. Room temperature. (A) Phase contrast micrograph. Precipitated crystals in a patient with cryocrystalglobulinemia. (B) Transmission electron micrograph of crystals.

VII.C.012

Cryocrystalglobulinemia. Scanning Electron Micrographs. (A)Characteristic long thin crystals at room temperature.(B) Leukocyte trapped in tangle of crystal network. (C) Appearance of crystals on a blood film at room temperature.

VII.C.013

Diffuse large B-cell lymphoma. H&E stained histologic section shows a diffuse infiltrate of neoplastic centroblasts with a high nuclear:cytoplasmic ratio, irregular nuclear contours, and prominent nucleoli. In addition, mitotic figures and apoptotic nuclei are seen, indicating a high proliferative rate in this tumor.

VII.C.014

Diffuse large B-cell lymphoma. CD20 immunostain shows diffusely positive staining on tumor cells, confirming a B-cell origin. Smaller reactive T lymphocytes are also present and unstained.

VII.C.015

Diffuse large B-cell lymphoma. Normal tissue architecture is replaced by a diffuse sheet of neoplastic centroblasts with large nuclei, a high nuclear:cytoplasmic ratio, and prominent nucleoli.

VII.C.016

Diffuse large B-cell lymphoma. CD20 immunostain confirms that neoplastic cells are of B-cell origin. Positive staining is denoted by a cytochemical reaction forming a brown insoluble product.

VII.C.017

Extranodal marginal cell lymphoma of mucosa-associated lymphoid tissue marginal zone lymphoma. Endoscopic gastric biopsy showing MALT lymphoma. (A) Small lymphocytes in gastric mucosa, a site normally devoid of lymphocytic cells and with no native lymphoid follicles except in states of chronic inflammation. Lymphocytes are also seen invading the epithelium (arrows). (B) CD20 immunostain confirms that the infiltrating lymphocytes are CD20+ B cells (arrows). PCR demonstrated a clonal rearrangement of the immunoglobulin heavy chain locus (clonal B-cell population). This subtype of lymphoma is linked to chronic gastritis caused by Helicobacter pylori infection, and these organisms can often be seen on tissue biopsy when in the chronic inflammatory stage. In this case, as in most cases of MALT lymphoma, no H pylori were seen histologically.

VII.C.018

Extranodal marginal cell lymphoma of mucosa-associated lymphoid tissue (MALT). Pulmonary lobe resection showing typical “fish flesh” appearance of lymphoma. In this case, the tumor is an extranodal marginal zone lymphoma of extranodal mucosa associated lymphoid tissue, so-called MALT lymphoma.

VII.C.019

Extranodal marginal cell lymphoma of mucosa-associated lymphoid tissue (MALT) marginal zone lymphoma. Section of lung shown in VII.C.046 showing lymphoepithelial lesion characteristic of MALT lymphoma. Epithelial cell layer (arrow) with infiltrate of small lymphocytes.

VII.C.020

Extranodal marginal cell lymphoma of mucosa-associated lymphoid tissue (MALT) marginal zone lymphoma. Salivary gland. High power view showing characteristic small lymphocytes with monocytoid B cell appearance infiltrating epithelial elements (so-called “lymphoepithelial lesions”).

VII.C.021

Follicular Lymphoma. Follicular lymphoma. Lymph node biopsy. Low power. H&E stain. Back-to-back follicular nodules that replace normal nodal tissue.

VII.C.022

Follicular lymphoma. Lymph node biopsy. Low power. H&E stain. Back-to-back follicular nodules that replace normal nodal tissue.

VII.C.023

Follicular Lymphoma. Follicular lymphoma. Lymph node. The major cell type in follicular lymphoma is a cleaved, small lymphocyte or centrocyte. Note lymphocytes with nuclear irregularities, some resembling folded or clefted nuclei (typical centrocyte appearance).

VII.C.024

Follicular lymphoma. Lymph node biopsy. High power view of the central portion of a neoplastic follicle showing small, cleaved cell cytology (centrocytes) as the predominant cell type. These are features associated with grade 1 histology using the 3 grade system in use by the World Health Organization Classification of Hematological Malignancy.

VII.C.025

Follicular lymphoma. Lymph node biopsy. Admixed amongst the centrocytes are scattered large cells with prominent nucleoli called centroblasts (arrow). Follicular lymphoma can be graded histologically based on the number of centroblasts from low grade (grade 1) to more aggressive (grade 3) cases. In the particular case illustrated, the majority of the tumor met criteria for histologic grade 2.

VII.C.026

Follicular lymphoma. CD20 immunostain. Lymph node section. The reddish-brown color reaction confirms a B-cell origin of the lymphoma cells.

VII.C.027

Follicular lymphoma. CD10 immunostain. Lymph node biopsy. Reddish-brown staining of neoplastic follicular cells, an immunophenotype that resembles normal germinal center B-cells.

VII.C.028

Follicular lymphoma. Lymph node biopsy. BCL-2 immunostain shows reddish-brown staining of neoplastic follicular cells. Normal germinal center cells are negative for BCL-2, an anti-apoptotic protein. In follicular lymphoma, tumor cells over express BCL-2 as a result of a t(14;18) translocation in which the BCL-2 gene locus is translocation next to the immunoglobulin heavy chain locus, resulting in constitutive over expression of this gene product.

VII.C.029

Follicular lymphoma, large cell type, histologic grade 3a. Lymph node biopsy. This specimen illustrates a case of follicular lymphoma at the more high-grade end of the histologic spectrum of cases. In grade 3a histology, more than 15 centroblasts can be seen per standard 40x (high power) microscopic field. In grade 3a, centroblasts are seen as single cells scattered within a background of centrocytes. In grade 3b, these centroblasts form large clusters or sheets. Survival curves in clinical trials have clearly established the more aggressive nature of grade 3 histology over grade 1 histology. More recent studies have suggested also that separation into grade 3a and grade 3b (as outlined above) may also help to predict more aggressive from more indolent cases within that particular subtype.

VII.C.030

Intravascular large B-cell lymphoma. Lung biopsy. H&E section. This rare type of large cell lymphoma shows neoplastic centroblasts in small blood vessels. The centroblasts remain confined to the intravascular space. Scattered microinfarctions are often present. Two arrows point to microvasculature plugged with tumor cells.

VII.C.031

Intravascular large B-cell lymphoma. Lung biopsy. Low power section. H&E stain. Note neoplastic centroblasts in microvasculature. (Two representative vessels indicated by arrows.)

VII.C.032

Lymphomatoid granulomatosis. (A) Angiocentric-angioinvasive and destructive lesion that is Epstein-Barr virus–driven and occurs commonly in lungs, liver, brain, and skin but can be seen at any site. This is a grade 1 lesion. The majority of background cells are reactive T cells. Lesions are graded on a scale of 1 to 3 based on the number of large cells and nuclear atypia. Grade 3 lesions are considered to be a form of large B-cell lymphoma, an aggressive neoplasm. (B) The admixed large CD20+ B cells are positive for Epstein-Barr virus latent RNA (EBER) as indicated by the blue-black nuclear reaction product in two B cells. The nuclei of non-reactive cells are stained pale pink.

VII.C.033

Mantle Cell Lymphoma. Mantle cell lymphoma. Lymph node biopsy. Low power. H&E stain. Sections show a nodular infiltrate of small lymphocytes that replace normal lymph node architecture. Unlike follicular lymphoma, true follicle formation is not present.