Chapter 12 Hematolymphoid disorders
INTRODUCTION
In general, hematolymphoid cells manifest as dyshesive cells in cytological specimens.25 However, this is not a hard and fast rule, and exceptions can occur in some instances either as a natural phenomenon or due to artifact. For example, it is known that lymphocytes in tuberculous effusions and in fine-needle aspirations (FNAs) of follicular lymphoma may form ‘lymphoid aggregates’.25,81 
An effusion-based lymphoma simulating carcinoma, even forming apparent ‘glands,’ ‘papillary’ structures, and cytoplasmic vacuoles, has been described in the case of a pleural anaplastic large cell lymphoma.27 Conversely, the cells of non-hematopoietic neoplasms, such as melanoma or desmoplastic small round cell tumor, can appear individually or in loose clusters mimicking a lymphoid neoplasm.8,38 The classic lymphoglandular bodies, representing remnants of lymphocyte cytoplasm, are typically inconspicuous or absent in effusion fluids, in contrast to FNA material from solid specimens.
After determining the lymphoid nature of the cells, the distinction between low-grade lymphoma and reactive lymphocytosis is often difficult by morphology alone, since cellular atypia is often minimal or absent. With high-grade lymphomas, the differential is usually between undifferentiated sarcoma and carcinoma. In most cases, an accurate diagnosis and classification can be achieved by integrating clinical history, cytologic findings, and immunophenotype with immunostains and/or flow cytometry (Table 12.1) along with molecular studies (see Chapter 13) as indicated.
Air-dried Diff-Quik (DQ)- or Wright–Giemsa-stained slides have traditionally been the stains of choice for hematopoietic cells, especially for examining subtle cytoplasmic details and variations (see Chapter 3). However, alcohol-fixed, Papanicolaou (PAP)-stained preparations are better for examination of nuclear detail. In addition to preparing well-stained smears and cell blocks, efforts should be made to save extra samples for ancillary studies such as flow cytometry and molecular studies when assessing possible hematopoietic neoplasms. The value of new cytologic preparations such as Thin-Prep has not been extensively evaluated in examining effusion cytology, particularly regarding hematopoietic cells.
EPIDEMIOLOGY
In adults within the United States, pleural, peritoneal, and pericardial effusions are most commonly related to benign conditions like congestive heart failure, cirrhosis of the liver, and pericarditis. Malignant effusions are most commonly secondary to the epithelial neoplasms (breast, lung, gastrointestinal, and genitourinary cancer). However, non-Hodgkin lymphoma accounts for approximately 10% of all malignant pleural effusions. After lung and breast carcinoma, lymphoma is the third most common cause of a malignant pleural effusion.47,74,83,85 In regards to malignant peritoneal effusions, lymphoma (7%) ranks third after ovary (32%) and breast (13%) carcinoma (see Table 9.2, Figure 9.3).47,74
The most common causes of malignant effusions in children are hematopoietic neoplasms. A study of 508 samples from patients under 18 years of age with serous effusions showed that pleural fluids represented the largest group, constituting 61.4% of the fluids, while ascitic fluid and pericardial fluid represented 25.6% and 7.5%, respectively. Of these 508 cases, 226 (44%) had a documented neoplasm. A positive cytology for neoplastic cells was found in 47.5%, 23.1%, and 42.9% from pleural, ascitic, and pericardial fluids, respectively. The most common tumor types associated with a positive cytology in children were lymphoma/leukemia (52%), neuroblastoma (14%), Wilms’ tumor (9%), germ cell neoplasms (8%), bone and soft tissue sarcomas (7%), epithelial neoplasms (5%), and Ewing’s sarcoma (2%). For each site with a positive cytology, the patients had lymphoma/leukemia in 57.6% of pleural fluids, 33.3% of ascitic fluids, and 100% of pericardial fluids. It is rare for a child to present with a malignant effusion without first having a tissue diagnosis.90
PLEURAL FLUID
Pleural fluid in normal, healthy, non-smoking adults typically consists of macrophages (median 75%), lymphocytes (median 23%), and mesothelial cells (median 1%). Neutrophils (median 0%) and eosinophils (median 0%) are only rarely present. This differential cell count appears to remain constant in patients aged from 17 to 54 years. The total pleural fluid volume in normal adult humans averages 0.26 ± 0.1 mL per kilogram body mass. Non-smokers have a median total white blood cell (WBC) count of 91 × 103/mL. In smokers, an increase in total WBC count (median 147 × 103/mL) and neutrophils (median 1%) can be seen.60,61 Normal pleural fluid cytology in children has not been studied to the same extent as it has been in adults.
PERICARDIAL FLUID
The composition of ‘normal’ pericardial fluid has been determined in patients undergoing elective heart surgery for coronary or valvular disease. Patients with prior (within 3 months) myocardial infarction, any known pericardial disease, systemic or autoimmune disease affecting pericardium, or use of medications associated with pericarditis were excluded from the study. These adult patients had a normal total serum WBC count with a normal leukocyte differential. The mean total pericardial WBC count was 1400/μL with a mean of 53% lymphocytes, 31% neutrophils, 12% monocytes, 1.7% eosinophils, and 1.2% basophils. Thus, a diagnosis of ‘lymphocytosis’ in pericardial effusions should be rendered cautiously.9
Malignant pericardial effusions in the adult are most commonly secondary to lung and breast carcinoma, but metastatic melanoma and lymphoma/leukemia are next in frequency.36,83 Most patients will have a clinical history of malignancy, but rarely pericardial effusion may be the initial presentation of disease. Cardiac involvement of systemic lymphoma has been reported in up to 20% of cases.13,83 Immunocytochemical stains for cytokeratin, S-100, HMB45, and CD45 should be performed when suspicion for a non-epithelial malignant effusion exists.36 Once a lymphomatous/leukemic effusion is favored by this panel, evaluation of the morphologic and immunophenotypic features described in the following sections should be used for further classification.
Pericardial effusions in children are rare. In a large study of serous fluid cytology specimens over a 40-year period, only 7.5% of the pediatric specimens were from pericardial fluid. The only positive malignant cytology in pericardial fluids in these patients was due to Hodgkin lymphoma.90
Fifteen percent of pericardial effusions were malignant. Hypothyroidism (9%), rheumatoid arthritis (7%), Coxiella burnetii (5%), enteroviruses (4%) and systemic lupus erythematosus (3%) were some other causes; 48% of pericardial effusions did not have an identifiable cause and remained ‘idiopathic.’50
LYMPHOCYTIC EFFUSIONS
A lymphocytic pleural effusion is defined as a lymphocyte differential cell count exceeding 50%.56 The lymphocytic effusions may be either transudative or exudative and reactive or neoplastic. The variation in type and etiology of the effusion depends on the patient population.
Lymphomatous and leukemic pleural effusions are classically exudative. Unusual cases of transudative effusions are seen in patients who have concomitant diseases such as renal failure or heart failure.5 Non-Hodgkin lymphoma accounts for approximately 10% of all malignant pleural effusions. Patients with non-Hodgkin lymphoma may develop a pleural effusion in 10–20% of cases,30,56 but in only 60–90% is a positive cytologic diagnosis made.30 The reason for negative cytology may be related to: (1) the effusion may be benign and secondary to obstruction of lymphatic drainage or (2) the patients may have concurrent unrelated disease causing an effusion.30 The patients with Hodgkin lymphoma may develop benign pleural effusions in up to 20% of cases due to obstruction of mediastinal or pulmonary lymphatic drainage.63
Non-Hodgkin lymphoma is a common cause of chylothorax, which is an accumulation of lymphatic fluid in the pleural space and is associated with increased pleural fluid triglyceride levels (greater than 110 mg/dL is highly suggestive of a chylous effusion).78 In over 50% of patients with a malignant effusion associated with a chylothorax, the malignant tumor is a lymphoma.83
REACTIVE LYMPHOCYTIC EFFUSIONS
Congestive heart failure
In regions with low rates of tuberculosis and/or with a high incidence of heart disease (e.g. the United States), congestive heart failure is the most common cause of lymphocytic effusions in adults. It results in a transudative lymphocytic effusion, and exudative effusions are rare.29
Pulmonary embolism
The differential WBC count in patients with pulmonary embolism is more often predominated by neutrophils (60% of patients), but in 40% of patients, lymphocytes predominate. Greater than 10% eosinophils can be seen in up to 18% of effusions secondary to pulmonary embolism. The effusion characteristically is an exudate and frequently shows increased mesothelial cells and red blood cells (RBCs).71
Syphilitic pleuritis
A single rare case of syphilitic pleuritis diagnosed by cytopathology reported involvement of the lung and pleura by Treponema pallidum, which resulted in a pleural effusion. The 68-year-old patient described in this report had been diagnosed previously with syphilis.92 Cytologic examination of the pleural fluid by alcohol-fixed PAP and air-dried Giemsa-stained smears showed many lymphocytes and smaller numbers of plasma cells. Aggregates of histiocytes with foamy cytoplasm were also present. In the Giemsa-stained preparations, rare purple-stained spirochetes could be seen free in the background and in the cytoplasm of histiocytes. In the later stages of syphilis, epithelioid granulomas may appear and the distinction from tuberculosis and sarcoidosis may be difficult. Dark-field illumination or immunofluorescent microscopy are superior methods to Giemsa staining in detecting spirochetes.
Viral pericarditis
Viral pericarditis is most commonly caused by Coxsackie B virus. Coxsackie virus, which belongs to the genus of enteroviruses, may cause a rapidly fatal myopericarditis. In some cases, the lymphocytes in the effusion fluid may be highly reactive and atypical.52 The differential diagnosis in such cases includes cardiac lymphoma, and ancillary studies should be performed to rule out a malignancy.
Tuberculosis
In regions with high tuberculosis rates, the most common etiology of lymphocytic pleural effusions is pulmonary infection with Mycobacterium tuberculosis.42,53,54,85 Tuberculosis is associated with an exudative effusion containing numerous (>50%) lymphocytes and usually very few mesothelial cells. 
The small lymphocytes may be numerous and difficult to distinguish from lymphoma or leukemia. The lymphocytes are virtually all T cells. Multinucleated giant cells are usually not seen in pleural fluid cytology but may be seen in 60–80% of pleural biopsies.19,83 The lymphocytes in tuberculous effusions can form lymphoid groups or clusters, presumably because of fibrin trapping.25 In some patients, pleural fluid may contain greater than 10% eosinophils (see section on eosinophilic effusions) and increased numbers of mesothelial cells.53
NEOPLASTIC LYMPHOCYTIC EFFUSIONS (TABLE 12.2)
Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
CLL is the most common leukemia in adults over 50 years old.41,79 CLL and SLL are now recognized as being two ends of the spectrum of a single disease distinguished only by the main site of neoplastic involvement. CLL by definition involves the peripheral blood and bone marrow at the time of diagnosis. Approximately 3.5% of CLL/SLL patients will eventually develop a high-grade lymphoma (Richter syndrome), which is most often a diffuse large B-cell lymphoma. Sheets of immunoblasts suggest transformation to a diffuse large B-cell lymphoma. CLL/SLL patients may also develop Hodgkin lymphoma in 0.5% of cases.41
Pulmonary complications are a common cause of morbidity and mortality in CLL patients. The most common pulmonary illnesses are pneumonia (75%), followed by malignant pleural effusion due to CLL (5%). 
In many cases with clinically suspected serous cavity involvement, if flow cytometry is not performed, the distinction from reactive lymphocytes may be difficult by cytology alone.1 Thus, the true incidence of malignant effusion secondary to CLL may be underestimated.
The classically described cytomorphology of CLL/SLL (see Table 12.1) is that of a neoplasm composed of mostly monomorphic, small, round lymphocytes with clumped chromatin, scant cytoplasm, and indistinct or absent nucleoli (Figure 12.1b,c). The chromatin pattern has been described as ‘soccer-ball-like.’ Compare the CLL/SLL lymphocyte with the cleaved centrocyte of a germinal center or in follicular lymphoma (Figure 12.1a). CLL/SLL, however, is also composed of varying numbers of prolymphocytes, paraimmunoblasts, and plasmacytoid lymphocytes that differ from the classically described small round lymphocyte. In tissue sections, these prolymphocytes and paraimmunoblasts collect to form ‘pseudo-follicles’ or ‘proliferation centers’ that can readily be seen as lighter areas on low-power magnification. Prolymphocytes are medium sized (approximately twice the size of a small lymphocyte), have a small but distinct nucleolus, and have an increased amount of cytoplasm. Paraimmunoblasts are medium to large cells (2–3 times a small lymphocyte) with round to oval nuclei, multiple peripheral nucleoli or a single large prominent central nucleolus, and slightly basophilic cytoplasm on Wright–Giemsa stain.17,41
The challenge in diagnosing a malignant effusion due to CLL/SLL stems from (1) distinguishing it from a reactive lymphocytosis and (2) determining whether there is contamination with peripheral blood lymphocytes secondary to a traumatic/bloody thoracentesis. The lymphocytes of CLL/SLL can be morphologically indistinguishable from reactive lymphocytes. This is because, as described above, the lymphocytes in CLL/SLL can be heterogeneous in the same way as reactive lymphocytes. A monomorphic population of small round lymphocytes, though, is suggestive of involvement by CLL/SLL.
Further support for diagnosis of CLL can be attained by making a cell block from extra serous fluid and performing immunohistochemical stains. 
Usually, reactive lymphocytes are predominantly CD3 positive T cells while a malignant pleural effusion due to CLL/SLL usually shows predominantly CD20 positive B cells. Aberrant expression of CD5 (the T-cell marker) in the B cells with co-expression of CD23 without cyclin-D1 will help confirmation of involvement by CLL/SLL (see Table 12.1). 
Furthermore, flow cytometry studies are extremely helpful and also much more sensitive at identifying a small population of monoclonal B cells that may not be evident by cytology or immunohistochemistry.
Caution should be exercised before making a diagnosis of a malignant CLL effusion until the possibility of a traumatic thoracentesis has been ruled out. This can be done by examining the fluid for significant numbers of RBCs. Blood containing leukemic cells can result in a false-positive diagnosis.19 It is also possible that the leukemic/lymphomatous infiltrate may directly infiltrate the pleura without producing a frankly malignant effusion. In this case, one will see reactive T cells in the serous fluid and a neoplastic B-cell infiltrate in the biopsy.57,82
Other ‘small’ B-cell lymphomas: follicular, mantle cell, marginal zone lymphoma, lymphoplasmacytic lymphoma
The previous discussion of malignant effusion diagnoses in CLL/SLL also applies to other small B-cell lymphomas such as follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma (including mucosa-associated lymphoid tissue lymphoma—MALT lymphoma).
That is to say, reactive versus neoplastic lymphoid proliferations of small lymphocytes in these lymphomas may be difficult, if not impossible, to separate by cytologic examination alone. The diagnostic accuracy for all lymphomas, even by FNA, varies from 64 to 91%, but for follicular lymphomas the diagnostic accuracy varies from 37 to 69%81
Immunohistochemistry, flow cytometry, and molecular studies are useful and may be critical ancillary tools when examining small lymphocytic proliferations.
Follicular lymphoma
Follicular lymphoma is the second most common lymphoma in the USA (35% of lymphoma) and worldwide (22% of lymphoma).41,79 It is twice as common in whites as in blacks. Only 9% of follicular lymphomas show extranodal involvement.35
Cytomorphologically, the characteristic lymphocyte of follicular lymphoma is the small-cleaved lymphocyte, also known as a centrocyte, which has a small indented nucleus, indistinct to absent nucleolus, and scant cytoplasm (see Figure 12.1a, Table 12.1). The characteristic feature of irregular nuclei in follicular lymphoma has been described as nuclear notches, nuclear projections, and nuclear clefts. In some cases, the nuclear irregularities may be subtle.17 However, the neoplasm is also composed of varying numbers of centroblasts, which are large cells with one to three small, peripherally located nucleoli and round to oval nuclei. 
As the grade of the lymphoma increases, the number of centroblasts also increases. Therefore, a heterogeneous population does not imply benignity. However, in many cases, centrocytes predominate (grade 1 follicular lymphoma), and thus give a monomorphic appearance. With grade 3 follicular lymphoma, centroblasts may predominate to the point of making the distinction from diffuse large B-cell lymphoma difficult. In most patients, however, grade 3 follicular lymphoma and diffuse large B-cell lymphoma are treated the same.70
Immunophenotypically, the lymphocytes of follicular lymphoma are positive for CD20, BCL-2, and CD10, while negative for CD5.41 The immunophenotypic findings are critical in confirming the diagnosis; however, they will not help in distinguishing a CD10-positive diffuse large B-cell lymphoma from a grade 3 follicular lymphoma (see Table 12.1).
Extranodal marginal zone lymphoma/mucosa-associated lymphoid tissue (MALT) lymphoma.
Extranodal marginal zone lymphoma represents 7–8% of non-Hodgkin lymphomas (NHLs).41,79 MALT lymphoma is common in the stomach and is associated with Helicobacter pylori infection. It also frequently involves the lung (14% of MALT lymphoma cases) and salivary gland, often associated with autoimmune diseases.
The heterogeneous lymphoid population in MALT lymphoma, in contrast to the classic monomorphic appearance of lymphoma cytology, can be misleading and result in a diagnosis of a reactive process.
Immunophenotypically, the diagnosis of marginal zone lymphoma/MALT lymphoma is one of exclusion since currently there is no specific immunophenotype. Marginal zone lymphoma/MALT lymphoma is positive for CD20 and negative for most other markers (CD10, CD5, BCL-1/cyclin D1, and CD23). The neoplastic cells frequently aberrantly express CD43 (a pan T-cell marker), a feature supportive of a neoplastic process. This finding is particularly useful when flow cytometry or molecular studies are not available to establish the clonality. Occasionally, they may express CD11c.21,41
Mantle cell lymphoma
Mantle cell lymphoma represents 3–10% of non-Hodgkin lymphomas. Despite its histologic resemblance to low-grade small cell lymphomas, it is considered an intermediate-grade lymphoma with a poor prognosis (median survival 3–5 years). The most common extranodal sites include bone marrow (>50%), gastrointestinal tract (30%), peripheral blood (25%), spleen, lung, pleura, and cerebrospinal fluid (9%).41,76,86
Cytomorphologically, the cells of mantle cell lymphoma typically resemble the centrocytes seen in follicular lymphoma; however, the nuclear irregularities are less pronounced and nucleoli are more frequently noted.17 In some cases, the small cleaved lymphocytes may closely resemble a follicular lymphoma centrocyte and thus a diagnosis of mantle cell lymphoma can be difficult, if not impossible, by cytologic examination alone.17 Mantle cell lymphoma is characterized by a monotonous population of small lymphocytes without admixed centroblasts or paraimmunoblasts. However, larger cells with immature lymphoblastic morphology (fine chromatin, nucleoli, and little cytoplasm) or larger, more pleomorphic cells with irregular nuclei and prominent nucleoli may appear in the so-called ‘blastoid’ variant of mantle cell lymphoma. The blastoid variant of mantle cell lymphoma is associated with an aggressive course. Rare cases with prolymphocytoid morphology have also been reported.
Immunophenotypically, the lymphocytes of mantle cell lymphoma can be shown to express nuclear BCL-1 (cyclin-D1), CD20, and the T-cell-associated markers CD5 and CD43. Cases of CD5 negative mantle cell lymphoma have been described and thus when mantle cell lymphoma is suspected, one should order immunohistochemistry for cyclin-D1. The neoplastic cells are characteristically CD10 negative, a feature distinguishing mantle cell lymphoma from follicular lymphoma. These cells are usually CD23 negative, in contrast to CLL/SLL. In cases with inconclusive immunophenotypic findings, fluorescent in-situ hybridization (FISH) for the t(11:14) translocation is extremely helpful to make the diagnosis.Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia
The cells of lymphoplasmacytic lymphoma consist of a mixture of small and larger lymphocytes with plasmacytoid features (basophilic cytoplasm, perinuclear clearing, eccentric nucleus). Dutcher bodies (intranuclear inclusions) and Russell bodies (intracytoplasmic inclusions) may be seen as a manifestation of accumulated immunoglobulins. Cytoplasmic light chain restriction can often be demonstrated by immunocytohistochemistry. Kappa restriction is more common than lambda.17
LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTRÖM MACROGLOBULINEMIA, defined by the 2001 World Health Organization (WHO), is a neoplasm involving bone marrow in which the neoplastic cells are positive for surface IgM and CD20 and negative for CD5, CD10, and CD23. By morphology alone, it may be difficult or impossible to differentiate lymphoplasmacytic lymphoma from marginal zone lymphoma without knowing bone marrow status or serum protein electrophoresis results. Lymphoplasmacytic lymphoma and marginal zone lymphoma appear closely related and they may reflect a spectrum of one disease.49,51
Burkitt lymphoma
Burkitt lymphoma is a mature B-cell malignancy that occurs most commonly in children (sporadic variant), immuno-deficient patients (primarily human immunodeficiency virus; HIV), and in parts of Africa (endemic variant). All cases of Burkitt lymphoma have a translocation of the MYC gene on chromosome 8. The most common translocation is t(8;14) but less commonly t(2;8) and t(8;22) may occur. Burkitt lymphoma also has interesting historical and etiologic association with Epstein–Barr virus (EBV). EBV was first discovered in Burkitt lymphoma cells sent to Epstein’s laboratory from Africa. These cells came from the endemic variant of Burkitt lymphoma, which has been shown to contain EBV DNA in 95% of cases. EBV is also seen in 25–40% of immunodeficiency-related cases and in 20% of sporadic cases of Burkitt lymphoma.41,48
The sporadic variant of Burkitt lymphoma occurs mostly in children and young adults. Sporadic Burkitt lymphoma represents 30–50% of childhood lymphomas. The majority of patients with sporadic Burkitt lymphoma (80–91% of patients) present with abdominal masses, which represent involvement of peritoneum, omentum, bowel mesentery, or bowel wall. The masses may continue to grow and involve breasts, ovaries, testes, kidney, liver, adrenals, and spleen.41,48 
Extensive involvement of the peritoneum may result in ascites. Ascites occurs in up to 58–90% of sporadic Burkitt lymphoma cases in the USA.37,48
Spread to pleura and pericardium may similarly give rise to serous effusions at those locations. Pleural and peritoneal effusions are seen more commonly than pericardial effusions. Ascites occurs in up to 58–90% of sporadic Burkitt lymphoma cases in the USA, while pleural effusions occur in 19–67%.37,48
The immunodeficiency-related variant of Burkitt lymphoma is primarily associated with HIV infection. In fact, Burkitt lymphoma may be the initial manifestation of acquired immune deficiency syndrome (AIDS) in some HIV-infected individuals.41 Burkitt lymphoma is more likely to occur early in AIDS, while diffuse large B-cell lymphoma occurs later in the illness. EBV is identified in 25–40% of Burkitt lymphoma cases in HIV-associated cases. Diffuse large B-cell lymphoma has a stronger association with EBV in AIDS patients than does Burkitt lymphoma. EBV is identified in 60% of all HIV-related lymphomas. Burkitt lymphoma represents 30% of all HIV-associated lymphomas.41,48
The diagnosis of Burkitt lymphoma can be an oncologic emergency, owing to its near 100% proliferation rate. The tumor cells have a doubling time of only 24 hours. This high growth rate may lead to ‘tumor lysis syndrome’ after initiation of therapy, which may cause renal failure and sudden hyperkalemia. Serous effusion cytology is the ideal specimen for this lymphoma in which a rapid diagnosis is required. Burkitt lymphoma not uncommonly causes pleural and peritoneal effusions for which cytologic examination is possible.37
Characteristically, Burkitt lymphoma is composed of strikingly monomorphic, non-cohesive, non-cleaved, medium-sized cells with regular nuclei, and prominent cytoplasmic vacuoles (see Table 12.1). The classic Burkitt lymphoma morphology is universally seen in the pediatric Burkitt lymphomas, but in adults, it more often has increased pleomorphism and therefore has been referred to as ‘atypical Burkitt/Burkitt-like lymphoma’.41,55 
The cytoplasmic vacuoles are most readily apparent on air-dried Wright–Giemsa or DQ-stained smears (Figure 12.2). While air-dried smears demonstrate excellent cytoplasmic detail, the monomorphism of the cells is less apparent with these preparations, which accentuate subtle differences in cell size and amount of cytoplasm, making them appear more pleomorphic than in alcohol-fixed smears or tissue sections. The characteristic cytoplasmic vacuoles in Burkitt lymphoma cells represent cytoplasmic lipid that can be stained with lipid stains such as oil red O. The chromatin pattern is clumped and many cells contain multiple (often 2–5) easily identifiable nucleoli. The thin rim of surrounding cytoplasm is deeply basophilic owing to the high RNA content. Mitotic figures may be readily identified (see Figure 12.2c). One may also see ‘tingible-body macrophages’ which have phagocytosed cellular debris from the rapidly dividing cells. These tingible-body macrophages impart the ‘starry-sky’ appearance seen in tissue sections and can be seen in any rapidly proliferating lymphoma.
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