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Lymphomas do not only only arise in lymph nodes. Many arise in non-lymphoid sites such as the skin and gastrointestinal tract. The gastrointestinal tract is the most common extra-nodal site for follicular lymphomas, the most common nodal based type of lymphoma.

Cutaneous Lymphomas
Enteropathy-type T-cell Lymphoma
Urinary Bladder Lymphomas
MALTOMA (Mucosal Associated Lymphoid Tissue Lymphomas)
Splenic Marginal Zone Lymphoma


Gross Appearance and Clinical Variants  
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Primary adrenal lymphoma.

Harris GJ, Tio FO, Von Hoff DD.

Department of Medicine, University of Texas Health Science Center, San Antonio 78284.

Cancer 1989 Feb 15;63(4):799-803 Abstract quote

A case of non-Hodgkin's lymphoma (large cell immunoblastic sarcoma) arising as a primary malignancy in the adrenal gland is reported and the literature concerning this unusual tumor is reviewed. Although extremely rare, it is possible to make the diagnosis preoperatively.

Therefore, primary adrenal lymphoma should be included in the differential diagnosis of a suprarenal mass.

Non-Hodgkin's lymphoma confined to the adrenal glands presenting with Addison's disease.

Khan S, Raby N, Michell M.

Department of Radiology, King's College Hospital, London.

Clin Radiol 1990 Jul;42(1):63-4 Abstract quote

We report an unusual case of Addison's disease which is unique in being diagnosed ante-mortem as being due to Non-Hodgkin's lymphoma of the adrenal glands. Both ante- and post-mortem examinations showed the lymphoma to be entirely confined to the adrenals.

Non-Hodgkin's lymphoma of the adrenal gland.

Choi CH, Durishin M, Garbadawala ST, Richard J.

Department of Pathology, Doctors Hospital, Massillon, OH 44646.

Arch Pathol Lab Med 1990 Aug;114(8):883-5 Abstract quote

Primary non-Hodgkin's lymphoma of the adrenal gland was diagnosed in a 64-year-old woman. The histologic and immunohistologic features are characteristic of a large-cell noncleaved lymphoma (B-cell origin). The patient died 3 weeks after right-sided adrenalectomy. The patient's family refused an autopsy.

Malignant lymphoma of the adrenal gland: its possible correlation with the Epstein-Barr virus.

Ohsawa M, Tomita Y, Hashimoto M, Yasunaga Y, Kanno H, Aozasa K.

Department of Pathology, Osaka University Medical School, Japan.

Mod Pathol 1996 May;9(5):534-43 Abstract quote

Initial manifestation of malignant lymphoma in the adrenal gland is a rare event, and clinical and pathologic features are not fully understood.

We conducted a nationwide study in Japan, and 20 patients with malignant lymphoma that showed initial and main manifestation in the adrenal gland were identified. Clinical and pathologic findings were summarized. In addition, the presence of the Epstein-Barr virus (EBV) genome in the tumor cells was examined by using polymerase chain reaction (PCR) and in situ hybridization (ISH), together with the immunohistochemical evaluation of the expression of latent membrane protein-1 (LMP-1). There were 13 men and seven women; their ages at admission ranged from 40 to 87 years (median, 65 yr). Fever, anemia, and elevation of lactic dehydrogenase levels were the common presenting findings. One patient had acquired immunodeficiency syndrome. Adrenal tumors were bilateral in 15 patients and unilateral (all in the left site) in five. Prognosis was very poor; all but two patients died within 1 year after admission. Histologically diffuse large cell type was the commonest type (14 specimens). Immunohistologically, 16 specimens were B-cell type, and one was T-cell type. Another three specimens showing no positive reaction for any antibodies were also judged as B-cell type on purely morphologic grounds. Prominent intravascular proliferation of tumor cells was found in five patients. PCR for EBV genomes gave positive results in five patients; the virus was subtyped as A in three patients and as B in two.

The ISH provided positive signals in nine samples, including all five specimens positive for PCR. Four of the nine cases with detectable EBV by PCR and/or ISH expressed LMP-1. The present study shows that adrenal lymphoma is EBV associated and has a B-cell phenotype.

Primary adrenal lymphoma: gallium scintigraphy and correlative imaging.

Truong B, Jolles PR, Mullaney JM.

Department of Radiology, Medical College of Virginia Hospitals; Virginia Commonwealth University, Richmond 23298, USA.

J Nucl Med 1997 Nov;38(11):1770-1 Abstract quote

Primary adrenal lymphoma is a rare entity, with only 16 cases reported in the last 40 yr. Although 67Ga scintigraphy has been extensively used to evaluate patients with other types of lymphomas, there are no reports of its use in patients with this disease entity.

A man with primary adrenal lymphoma and no evidence of extraadrenal spread who was evaluated from presentation to remission with gallium scintigraphy and CT is presented. Gallium scintigraphy was valuable in assessing response to therapy.

Clinically silent primary adrenal lymphoma: a case report and review of the literature.

Wang J, Sun NC, Renslo R, Chuang CC, Tabbarah HJ, Barajas L, French SW.

Department of Pathology, Harbor-UCLA Medical Center, Torrance, California 90509, USA.

Am J Hematol 1998 Jun;58(2):130-6 Abstract quote

Primary adrenal lymphoma (PAL) is extremely uncommon.

We describe a case of clinically silent non-Hodgkin's B-cell lymphoma of diffuse large cell type with exclusive left adrenal localization. The tumor was discovered by computed tomography (CT) as a 2.5-cm dense mass and diagnosed at autopsy. Literature concerning this unusual neoplasm is reviewed. During the early stage, particularly when the lesion is small, PAL is likely to be missed.

This unusual entity should be included in the differential diagnosis of adrenal masses so that early diagnosis may be made and intervention might dramatically affect the clinical outcome.

A case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.

Lee KS, Chung YS, Park KH, Kim HS, Kim HM.

Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea.

Yonsei Med J 1999 Jun;40(3):297-300 Abstract quote

Unilateral or bilateral non-Hodgkin's lymphomas arising primarily in the adrenal glands are extremely rare. These lymphomas are usually present with large, bilateral adrenal masses with or without lymphadenopathy, and may be accompanied by adrenal insufficiency in some cases. A review of the literature indicates that patients with primary lymphoma of the adrenal glands usually do not have disease elsewhere, and if present, it is frequently extranodal.

We report here an unusual case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.


Diffuse large B-cell lymphoma of bone: an analysis of differentiation-associated antigens with clinical correlation.

de Leval L, Braaten KM, Ancukiewicz M, Kiggundu E, Delaney T, Mankin HJ, Harris NL.

Department of Pathology, Massachusetts General Hospital, Boston, 02114, USA.
Am J Surg Pathol. 2003 Sep;27(9):1269-77. Abstract quote  

Twenty-nine patients with diffuse large B-cell lymphomas presenting with bone involvement, including 18 localized primary bone lymphomas (group 1), 2 multifocal primary bone lymphomas (group 2), and 9 patients with extraskeletal disease at diagnosis (group 3), were studied.

The tumors were subclassified according to the criteria of the WHO classification and evaluated by immunohistochemistry for expression of antigens associated with germinal center (GC) and non-GC stages of B-cell differentiation (bcl-6, CD10, MUM-1, VS38c, CD138, bcl-2, and CD44). The presence of a BCL-2/IgH gene rearrangement was investigated by polymerase chain reaction. All cases were characterized by similar clinicopathologic and morphologic features and had similarly good overall outcome. The patients (23 males, 6 females, median age 44 years) had tumors in long bones (14), axial skeleton (8), limb girdles (3), and multiple sites (4). Most tumors (24) were centroblastic, with multilobated cells in 12 cases.

Almost half of the tumors (14 of 29, 48%) were bcl-6+CD10+ (GC-like), 9 of 29 cases (31%) were bcl-6+CD10- (indeterminate phenotype), and 6 of 29 cases (21%) were CD10-bcl-6- (post-GC like). The indeterminate phenotype was seen only in primary bone lymphoma. MUM-1 was frequently expressed in GC-like and non-GC-like categories. We found no evidence of plasmacytic differentiation by CD138, and VS38c immunoreactivity was distinctly rare (2 of 29 cases). CD44 was detected in 6 tumors, all CD10-. Bcl-2 was expressed by 70% of the tumors, but only 1 of 23 cases tested had a Bcl-2/JH rearrangement by polymerase chain reaction. A survival analysis showed that GC-like tumors had a longer overall survival duration compared with non-GC-like tumors (P = 0.0046).

In conclusion, a GC-like immunophenotype characterizes roughly half of large B-cell lymphomas of bone and is associated with an improved survival.

An Immunophenotypic and Molecular Study of Primary Large B-Cell Lymphoma of Bone

David Huebner-Chan, M.D., Bernie Fernandes, M.B., Ch.B., Guisheng Yang, M.D. and Megan S. Lim, M.D., Ph.D.

Department of Pathology (DH-C)Kaiser Permanente Medical Center, Anaheim, California; Department of Pathology (BF), Mount Sinai Hospital; and Sunnybrook and Women’s College Health Sciences Center (GY, MSL), University of Toronto, Toronto, Canada


Mod Pathol 2001;14:1000-1007 Abstract quote

Primary non-Hodgkin’s lymphomas of bone (PNHLB) is a rare form of extranodal lymphoma.

Many studies have reported the clinical, radiologic, and histopathologic characteristics of PNHLB; however, their molecular features have not been well studied. In this report, we present the immunophenotypic and molecular characteristics of 20 primary large B-cell lymphoma (PLBCL) of bone from 20 adults. Most demonstrated centroblastic morphology, with the majority exhibiting nuclear multilobation. One case (5%) demonstrated anaplastic features with strong CD30 expression but was ALK-1 negative. BCL-6 expression was seen in 6 of 20 cases, and strong p53 protein expression was seen in 11 of 20 (55%) cases. The majority of cases analyzed (13/18 = 72%) demonstrated a clonal B-cell process by IgH gene rearrangement studies. Of the five cases that did not demonstrate a clonal population, two expressed BCL-6 protein. No cases demonstrated a bcl-2/JH rearrangement, but BCL-2 protein expression was seen in 11 of 20 (55%) cases.

In summary, primary lymphoma of bone is largely a non-Hodgkin’s lymphoma of large B-cell type. Our studies demonstrate that p53 and BCL-2 expression may play a role in the pathogenesis of PLCBL of bone. In addition, a subset of the cases are of putative germinal center B-cell origin based on the expression of BCL-6 protein and may be genetically distinct from follicle center lymphomas. The results provide evidence for molecular heterogeneity within primary large B-cell lymphomas of bone.

Primary breast lymphoma cytologic diagnosis.

Vardar E, Ozkok G, Cetinel M, Postaci H.

Department of Pathology, SSK Izmir Teaching Hospital, Izmir, Turkey.
Arch Pathol Lab Med. 2005 May;129(5):694-6. Abstract quote  

Primary non-Hodgkin lymphoma of the breast is a rare pathology, and bilateral involvement is exceptional. We report a case of bilateral primary non-Hodgkin lymphoma of the breast in a 40-year-old woman. Predominantly atypical lymphocytes and rare plasma cells were found in the microscopic evaluation of the fine-needle aspiration biopsy of the right and left breasts.

Microscopic findings of the incisional biopsy of the left breast were in accordance with non-Hodgkin diffuse large B-cell lymphoma. The patient received systemic chemotherapy and is alive with no evidence of recurrence for 2 years.
Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype.

Yoshida S, Nakamura N, Sasaki Y, Yoshida S, Yasuda M, Sagara H, Ohtake T, Takenoshita S, Abe M.

[1] 1Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan [2] 2First Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Mod Pathol. 2005 Mar;18(3):398-405. Abstract quote  

Primary breast diffuse large B-cell lymphoma has a poor prognosis relative to other extranodal diffuse large B-cell lymphoma. Recently, diffuse large B-cell lymphoma has been subclassified as germinal center B-cell-like and nongerminal center B-cell types using tissue microarrays. The 5-year overall survival rate of the germinal center B-cell group is better than that of the nongerminal center B-cell group.

To elucidate the reason for which primary breast diffuse large B-cell lymphoma has a poor clinical outcome, we investigated 15 patients with primary breast diffuse large B-cell lymphoma (stage IE; 13 cases, stage IIE; two cases) by immunohistochemistry using various markers including CD10, Bcl-6, MUM1 and MIB-1 and by molecular analysis of the immunoglobulin heavy chain gene variable region. Immunohistochemistry showed 0/15 (positive cases/examined cases) for CD10, 5/15 for Bcl-6, 15/15 for MUM1, 10/15 for Bcl-2, 2/15 for CD5 and 4/15 for CD40. The expression pattern of CD10(-) MUM1(+) in primary breast diffuse large B-cell lymphoma corresponded to the nongerminal center B-cell group. Moreover, the MIB-1 index was distributed from 60 to 95% with a mean of 79%, indicating a high proliferation of the lymphoma cells. The immunoglobulin heavy chain gene variable region of primary breast diffuse large B-cell lymphoma had a mutation frequency of 1-10% (seven cases) and 0-1 additional mutations in ongoing mutation analysis (five cases). Primary breast diffuse large B-cell lymphoma had characteristics of the nongerminal center B-cell group.

In conclusion, primary breast diffuse large B-cell lymphoma has a nongerminal center B-cell phenotype and has a high MIB-1 index. These features might therefore be associated with poor prognosis.
Lymphomatosis cerebri as a cause of white matter dementia.

Rollins KE, Kleinschmidt-Demasters BK, Corboy JR, Damek DM, Filley CM.

Hum Pathol. 2005 Mar;36(3):282-90. Abstract quote  

Summary Primary central nervous system lymphoma most often presents as a solitary, isolated lesion in immunocompetent patients. Rarely, the disease presents as a diffuse, infiltrating condition without formation of a cohesive mass, a pattern called lymphomatosis cerebri.

We present 3 immunocompetent individuals who developed rapidly progressive dementia. Magnetic resonance imaging features mimicked other disorders of white matter and prompted preoperative diagnoses of Binswanger's disease (subcortical ischemic vascular dementia), unknown leukoencephalopathy, viral infection, or infiltrating glioma. Neuropathologic examination at biopsy (Poon T, Matoso I, Tchertkoff V, Weitzner I Jr, Gade M. CT features of primary cerebral lymphoma in AIDS and non-AIDS patients. J Comput Assist Tomogr . 1989;13:6-9) and autopsy (Schwaighofer BW, Hesselink JR, Press GA, Wolf RL, Healy ME, Berthoty DP. Primary intracranial CNS lymphoma: MR manifestations. Am J Neuroradiol . 1993;10:725-9) demonstrated nonnecrotic, diffusely infiltrating, large-cell B-cell lymphoma of white matter, with relative sparing of gray matter, and without significant leptomeningeal involvement or bulky periventricular disease at autopsy. Microglial and astrocytic reactions, but only subtle myelin pallor, were evident as individual tumor cells permeated the entire brain and spinal cord, albeit with considerable variation in cell density. Individual tumor cells could be identified from the optic nerve to spinal cord, documenting the "whole-brain" nature of the disease.

CD20 immunostaining was necessary to fully appreciate the extent of individual lymphoma cell percolation through the white matter. The neurobehavioral deficits manifested by these patients demonstrate that lymphomatosis cerebri is an additional neoplastic cause of white matter dementia and can be added to the growing list of disorders responsible for this syndrome.

Primary central nervous system lymphoma in Korea: comparison of B- and T-cell lymphomas.

Choi JS, Nam DH, Ko YH, Seo JW, Choi YL, Suh YL, Ree HJ.

Am J Surg Pathol. 2003 Jul;27(7):919-28. Abstract quote

The great majority of primary central nervous system lymphoma (PCNSL) is known to be of B-lineage, with T-cell PCNSL (T-PCNSL) accounting for <5%.

We report an unusually high incidence of T-cell lymphoma among the PCNSLs originated in a large general-care hospital in the metropolitan Seoul area. PCNSLs (n = 42) accrued from April 1995 through June 2001 were reviewed for histologic and clinical features, and immunohistochemical staining was done for CD3, CD20, CD4, CD8, Bcl-6, and CD10. Clonal rearrangements of the TCR-gamma and IgH genes were studied with semi-nested PCR in all seven cases of T-PCNSL and seven of 35 B-cell PCNSL (B-PCNSL). Formalin-fixed, paraffin-embedded specimens were used in all these studies.

By immunohistochemical staining and molecular studies, seven cases (16.7%) were diagnosed as T-PCNSL, each displaying clonal rearrangement of the TCR-gamma gene, and 35 (83.3%) as B-PCNSL. Radiologically, T-PCNSL was significantly correlated with the superficial and subcortical lobar location (p <0.001), solitary mass formation (p = 0.001), presence of rim enhancement (p <0.001), and peritumoral edema (p = 0.029). Involvement of cerebrospinal fluid was observed only in B-PCNSL (n = 17) but not in T-PCNSL (p = 0.010).

Histologically, T-PCNSL was characterized by a population of mixed predominantly small- and occasionally medium-sized cells (p <0.001), which were loosely scattered without forming a solid mass (p = 0.024), and perivascular infiltration was frequent (p = 0.007), in contrast to predominantly large cells of B-PCNSL, i.e., diffuse large B-cell lymphoma (DLBCL), in which the cells tended to aggregate to form monomorphous sheets (p = 0.024). In T-PCNSL, staining for CD8 was positive in five, including one with coexpression of CD4, and two were negative for CD4 and CD8. Of 24 DLBCLs tested, the pattern of Bcl-6+ tumor cells was diffusely dense, similar to that of the germinal center in nine cases (37.5%), with coexpression of CD10 in three of the nine cases. T-PCNSL accounted for 16.7% of the PCNSLs; thus, in Korea it may not be as rare as previously known.

The T-PCNSL presented with certain clinical and pathologic features that were distinct from B-PCNSL and displayed preponderance of CD8 expression. DLBCL of the germinal center B-cell derivation defined by bcl-6 expression comprised 37.5% of DLBCL of the brain.

Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals.

Chang CC, Kampalath B, Schultz C, Bunyi-Teopengco E, Logan B, Eshoa C, Dincer AP, Perkins SL.

Department of Pathology, Medical College of Wisconsin, Milwaukee 53226, USA.

Arch Pathol Lab Med 2003 Feb;127(2):208-12 Abstract quote

CONTEXT: Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) in immunocompetent individuals, although rare, has been rising in incidence. Currently, no reliable prognostic markers are available for these individuals.

OBJECTIVE: To study the implications of expression of a panel of oncogenic proteins (Bcl-2, Bcl-6, and c-Myc) and p53 for predicting clinical outcome, particularly overall survival, in immunocompetent individuals with primary CNS DLBCL.

DESIGN: Fourteen primary CNS DLBCL cases were retrospectively studied by immunohistochemistry on formalin-fixed, paraffin-embedded sections for the expression of c-Myc, Bcl-2, Bcl-6, and p53.

RESULTS: The overall frequencies of expression for p53, c-Myc, Bcl-2, and Bcl-6 in these cases were 29%, 50%, 71%, and 57%, respectively. Cases with expression of p53, c-Myc, or Bcl-6 had a poorer overall survival than those without (Kaplan-Meier survival analysis: 50% cumulative overall survival, 2 months vs 30-60 months, P =.02, log-rank test; 9-16 months vs 21-60 months, P =.03, log-rank test; and 9-16 months vs 21-60 months, P =.16, log-rank test, respectively). The expression of Bcl-2 or proliferation activity by MIB-1 showed no correlation with overall survival. Likewise, the clinical parameters, including age, location of tumors, multiplicity of tumor lesions, and lactase dehydrogenase levels revealed no impact on overall survival.

CONCLUSION: Our results suggest that patients with expression of p53, c-Myc, or Bcl-6 have a poorer overall survival than those without. Since traditional prognostic markers in non-CNS DLBCL, such as staging and International Prognostic Index scores, are not applicable to primary CNS DLBCL, evaluation of p53, c-Myc, and Bcl-6 by immunohistochemistry may be warranted as part of prognostic evaluation in immunocompetent patients with primary CNS DLBCL. Further studies are indicated to confirm our observations.


API2-MALT1 fusion gene in colorectal lymphoma.

Sakugawa ST, Yoshino T, Nakamura S, Inagaki H, Sadahira Y, Nakamine H, Okabe M, Ichimura K, Tanimoto M, Akagi T.

Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.

Mod Pathol. 2003 Dec;16(12):1232-41 Abstract quote.  

The API2-MALT1 fusion gene was originally identified from a t(11;18)(q21;q21) translocation, a specific chromosomal abnormality that is found in mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric MALT lymphomas positive for the API2-MALT1 fusion gene do not respond to Helicobacter pylori-eradication therapy, but otherwise, the incidence and clinicopathological behavior of colorectal MALT lymphoma with this genetic abnormality are unclear.

We examined the API2-MALT1 fusion by multiplex RT-PCR method in 47 cases of MALT lymphoma and 13 cases of diffuse large B-cell lymphoma and evaluated the relevance of API2-MALT1 positivity to the clinical and pathological features. The mean ages of MALT lymphoma and diffuse large B-cell lymphoma patients were 65 (range, 37-87 y) and 58 (range, 14-85 y) years, respectively. API2-MALT1 fusion genes were detected in seven cases (15%) of MALT lymphoma and one case (8%) of diffuse large B-cell lymphoma. In MALT lymphomas, the tumor size in API2-MALT1-positive cases was 62 +/- 39 mm (mean +/- SD), statistically larger than that in API2-MALT1-negative cases (25 +/- 19 mm; P <.01). The API2-MALT1-positive cases demonstrated more advanced clinical stages and a male predominance, compared with API2-MALT1-negative cases.

Thus, API2-MALT1-positive tumors should be cared for as a more aggressive subgroup and be followed for a longer time.
Lymphoma of the Ocular Adnexa: A Study of 353 Cases.

*James Homer Wright Pathology Laboratories of the Massachusetts General Hospital daggerDepartment of Pathology, Harvard Medical School double daggerDepartment of Radiation Oncology, Massachusetts General Hospital, Boston, MA section signOculoplastics Service, University of Wisconsin-Madison, Madison, WI.


Am J Surg Pathol. 2007 Feb;31(2):170-184. Abstract quote

We studied the cases of 353 patients with lymphoma involving the ocular adnexa diagnosed at the Massachusetts General Hospital between 1974 and 2005. The patients included 153 males and 200 females, aged 7 to 95 years, with a mean age of 64 years. In 277 cases, there was no known history of lymphoma.

Seventy-six patients had a history of lymphoma, with the ocular adnexa being involved at relapse or with progression of the previously diagnosed lymphoma. The patients had marginal zone lymphoma (182 cases), follicular lymphoma (80 cases), mantle cell lymphoma (18 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (13 cases), lymphoplasmacytic lymphoma (4 cases), splenic marginal zone lymphoma (2 cases), low-grade B cell, not subclassified (19 cases), precursor B lymphoblastic lymphoma (3 cases), diffuse large B-cell lymphoma (26 cases), and 1 case each of high-grade B-cell lymphoma, not subclassified, peripheral T-cell lymphoma, unspecified type, extranodal NK/T-cell lymphoma, nasal type, and Hodgkin lymphoma, nodular sclerosis type. Almost all marginal zone lymphoma patients (168 of 182, 92%) had primary ocular adnexal lymphoma. Fourteen marginal zone lymphoma patients (8%) had a prior history of lymphoma, usually arising in another extranodal site. Twenty-five of 80 (31%) follicular lymphoma patients had a prior history of lymphoma, usually arising in lymph nodes.

Patients with mantle cell lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and splenic marginal zone lymphoma almost always had a prior history of lymphoma or were known to have widespread disease at the time of diagnosis of ocular adnexal lymphoma.

A subset of the diffuse large B-cell lymphomas were associated with large destructive masses involving adjacent structures such as paranasal sinuses, raising the possibility that they may have arisen from one of the adjacent structures and involved the ocular adnexa by direct extension.

The relatively high proportion of low-grade lymphoma, not subclassified, highlights the difficulty that may arise in distinguishing different types of low-grade lymphoma, particularly when biopsies are small and artifactually distorted.

Ocular adnexal lymphoma is primarily a disease of older adults, with a slight female preponderance. Most lymphomas are low-grade B-cell lymphomas, with marginal zone lymphoma being by far the most common type. Marginal zone lymphoma typically involves the ocular adnexa primarily, whereas other types of low-grade B-cell lymphoma often involve the ocular adnexa secondarily. High-grade B-cell lymphomas only occasionally involve the ocular adnexa, and T-cell lymphoma, NK-cell lymphoma, and Hodgkin lymphoma are only rarely encountered in this site.

Involvement of the Chromosomal Translocation t(11;18) in Some Mucosa-Associated Lymphoid Tissue Lymphomas and Diffuse Large B-Cell Lymphomas of the Ocular AdnexaEvidence from Multiplex Reverse Transcriptase-Polymerase Chain Reaction and Fluorescence In Situ Hybridization on Using Formalin-Fixed, Paraffin-Embedded Specimens.

Takada S, Yoshino T, Taniwaki M, Nakamura N, Nakamine H, Oshima K, Sadahira Y, Inagaki H, Oshima K, Tadaatsu A.

Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama (ST, TY, AT).


Mod Pathol 2003 May;16(5):445-52 Abstract quote

The chromosomal translocation t(11;18) is a unique chromosomal aberration associated with mucosa-associated lymphoid tissue lymphoma. API2 and MALT1 genes have been identified around this translocation. We attempted to find chromosomal abnormalities focusing mainly on the t(11;18) translocation in formalin-fixed, paraffin-embedded tissues of ocular adnexal lymphoproliferative disorders using multiplex reverse transcriptase-polymerase chain reaction and/or two-color interphase fluorescence in situ hybridization.

By these methods, the t(11;18) translocation was detected in 1 of 8 patients with reactive lymphoid hyperplasia (13%), 3 of 23 with mucosa-associated lymphoid tissue lymphoma (13%), and 2 of 14 with diffuse large B-cell lymphoma with/without mucosa-associated lymphoid tissue lymphoma (14%). Moreover, we performed fluorescence in situ hybridization analysis to detect any numerical aberration of chromosomes 3, 7, 12, and 18 on some specimens nonselectively. No numerical chromosomal abnormalities were detected in 3 cases of reactive lymphoid hyperplasia, whereas three of four cases of mucosa-associated lymphoid tissue lymphoma and all four cases of diffuse large B-cell lymphoma with/without mucosa-associated lymphoid tissue lymphoma components exhibited one or more abnormalities.

These findings indicate a possibility that at least in the ocular adnexa, some diffuse large B-cell lymphomas are derived from mucosa-associated lymphoid tissue lymphomas.

GASTROINTESTINAL TRACT Most common location of extranodal follicular lymphomas
Molecular analysis of gastric washings in the diagnosis and monitoring of gastric lymphomas.

Chen B, Colleoni GW, Salazar PA, Lal P, Gerdes H, Filippa DA.
Hum Pathol. 2004 May;35(5):582-6. Abstract quote  

The monitoring of gastric lymphomas is often hampered by the inherently limited sampling provided by small endoscopic biopsy specimens.

To investigate the feasibility of using gastric washing fluid for monitoring patients with known gastric lymphoma and for diagnosing gastric involvement in patients with extranodal nongastric lymphoma, we collected 49 gastric washings from 39 patients (29 patients with gastric lymphoma and 10 patients with nongastric extranodal lymphoma). Collection was done at the time of follow-up biopsy and when no endoscopic abnormalities were found. DNA was extracted from the washing fluid and analyzed for clonal IgH gene rearrangement by Southern blotting (J6 probe) and/or polymerase chain reaction (PCR) (using VH-FR3 and JH primers).

Forty-one of 49 samples (84%) yielded sufficient DNA for molecular analysis. Sixteen of 41 analyzable gastric washing samples (39%) failed Southern blot analysis due to degraded or insufficient DNA. Concordance between the results of Southern blot analysis of the washing and histology of the simultaneous biopsy specimen was found in 20 (80%) of the remaining 25 samples. The IgH PCR result was concordant with biopsy histology in 33 out of 41 washing samples (80%). The overall concordance between molecular clonality studies of washings (Southern blotting and/or PCR) and biopsy histology was 83% (34 of 41). Of the 7 (18%) discrepant specimens, 2 were diagnosed histologically as lymphoma, but the simultaneous washings were negative by molecular studies.

Five biopsy specimens were histologically benign, but the corresponding washings demonstrated clonal IgH gene rearrangement (3 cases by PCR and 2 cases by Southern blotting). This study demonstrates the diagnostic utility of molecular clonality analysis of gastric washings.

Lymphoid lesions of the gastrointestinal tract: a histologic, immunophenotypic, and genotypic analysis of 49 cases.

O'Sullivan MJ, Ritter JH, Humphrey PA, Wick MR.

Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University Medical Center, St. Louis, Missouri 63110-1093, USA.

Am J Clin Pathol 1998 Oct;110(4):471-7 Abstract quote

The diagnosis of gastrointestinal (GI) lymphoid infiltrates can be challenging when based only on conventional microscopic assessment. When marked cytologic atypia is present, a diagnosis of malignant neoplasm is readily made; however, the distinction between a low-grade malignant neoplasm and a reactive process is much more difficult. If unfixed tissue is available, immunohistologic or genotypic methods that are usually aimed at defining B-lymphocytic monotypism can be applied. However, paraffin-embedded tissue has generally been deemed unsuitable for these techniques.

We assessed the value of a panel of immunohistochemical stains and a seminested polymerase chain reaction (PCR) for the analysis of lymphoid infiltrates in routinely processed GI biopsy specimens from 49 archival cases, including morphologically benign, indeterminate, and overtly malignant lesions.

Clinical outcome was used as the retrospective diagnostic standard; end points were death (of lymphomatous disease or otherwise) and clinical evidence of lymphoma. According to light microscopic criteria, 19 cases were classified as benign, 17 as malignant, and 13 as atypical. Immunophenotyping correctly identified 28 of 31 benign and 14 of 18 malignant lesions (7 cases had an indeterminate immunoprofile). Genotypic analysis correctly identified 12 of 18 malignant and 29 of 31 benign lesions, but spurious monoclonal bands were produced by PCR amplification of 2 of the latter 31 cases.

No single technique exists for correct categorization of all paraffin-embedded specimens of GI lymphoid infiltrates. We recommend a sequential approach to the use of available diagnostic modalities.

Increased Incidence of Follicular Lymphoma in the Duodenum

Tadashi Yoshino, M.D., Ph.D.; Kenji Miyake, M.D., Ph.D.; Koichi Ichimura, M.D.; Tomohiko Mannami, M.D.; Nobuya Ohara, M.D., Ph.D.; Shuji Hamazaki, M.D., Ph.D.; Tadaatsu Akagi, M.D., Ph.D.

From the Departments of Pathology (T.Y., K.M., K.I., T.M., N.O., T.A.) and Central Laboratory (S.H.), Okayama University Medical School, Japan.

Am J Surg Pathol 2000;24:688-693 Abstract quote

The incidence of indolent lymphomas in the lymph nodes and extranodal regions is quite different. Follicular lymphoma (FL) is most common in the nodes, and it seems to be least common in the gastrointestinal (GI) tract, where mucosa-associated lymphoid tissue lymphoma arises most frequently.

The authors report that the incidence of FL is unexpectedly high in the duodenum compared with other portions of the GI tract. FL was detected in only eight of 222 cases of GI lymphoma (3.6%). However, five cases of FL arose in the duodenum, which accounted for 38.5% of 13 duodenal lymphomas. Only in two patients did FL arise in either the stomach or the colorectum, and in the remaining patients FL was widespread with lymphomatous polyposis.

Duodenal FL was composed of neoplastic follicles with small cleaved cells in dominance, and the immunophenotype of the lymphoma cells was CD10+, BCL-2+, CD20+, CD75+, CD79+, CD3–, CD5–, cyclin D1–, CD23–, and CD45RO–.

All the patients were women age 37 to 66 years (average age, 52.4 yrs). In all patients the lymphoma was present around the ampulla of Vater, and four of five patients showed multiple small-size polyps. Although lymphoma cell infiltration was confined to the submucosa in the four patients examined, the regional lymph nodes were involved partially in two patients without distant metastasis. All patients are alive at 2 to 50 months of follow up (average, 27 mos), which is comparable with the prognosis for indolent nodal lymphomas.

These results suggest that the duodenum has a distinct background of histogenesis of the lymphomas and that biopsy specimens from the duodenum with multiple polyps should be examined carefully.

Primary Follicular Lymphoma of the Gastrointestinal Tract
A Clinical and Pathologic Study of 26 Cases

Jinru Shia, M.D. ; Julie Teruya-Feldstein, M.D. ; Dorothy Pan, M.D. ; Abhijith Hegde, M.D. ; David S. Klimstra, M.D. ; R. S. K. Chaganti, Ph.D. ; Jing Qin, Ph.D. ; Carol S. Portlock, M.D. ; Daniel A. Filippa, M.D.

From the Departments of Pathology (J.S., J.T.-F., D.S.K., D.A.F.), Medicine (D.P., A.H., R.S.K.C., C.S.P.), and Biostatistics (J.Q.), Memorial Sloan-Kettering Cancer Center, New York, NY, U.S.A.

Am J Surg Pathol 2002;26:216-224 Abstract quote

Although the gastrointestinal tract represents the most common site of extranodal lymphoma, primary follicular lymphoma of the gastrointestinal tract is an uncommon and poorly defined disease.

We report the clinical and pathologic features of 26 patients with primary gastrointestinal follicular lymphoma. Ten of 26 patients (38.5%) were stage IIE, and 16 patients (61.5%) were stage IE. Of the 26 patients, 13 were female and 13 were male. The age range was 26–81 years (median 54.5 years). Abdominal pain was the most common presenting symptom, seen in 12 of 24 patients (50%). Nodularity of the mucosal surface was the most common endoscopic finding, seen in 10 of 14 patients (71.4%). The majority of cases (22 of 26, 84.6%) involved small bowel, four involved colorectum alone, and two involved the ileocecal valve. Within the small bowel the duodenum was the most commonly involved site (10 cases). Transmural involvement by follicular lymphoma was identified in 11 of the 16 patients who underwent surgical resection; five showed involvement of mucosa and submucosa only. The most common histologic grade was grade 1. Thirteen of 26 cases were grade 1, ten grade 2, and three grade 3. Twenty-one of 26 cases showed a predominantly follicular growth pattern, four mixed follicular and diffuse, and one predominantly diffuse. All cases were positive for CD20 and BCL2 and negative for CD3, CD5, CD23, CD43, and cyclin D1. Twenty-four of 26 were positive for CD10. Four of four cases showed cytogenetic or molecular genetic evidence of t(14;18). Initial treatment modalities included surgery plus chemotherapy (nine cases), surgery alone (seven cases), chemotherapy alone (four cases), observation alone (four cases), and chemotherapy and abdominal radiation (one case). One case presented with rectal polyps and was treated with polypectomy. A complete response was observed in 15 of 22 cases that received treatment, and of the 15 cases, five recurred 27–60 months after the initial diagnosis. Recurrence and progression were associated with histologic transformation to diffuse large cell lymphoma in one case. No significant correlation was identified between treatment response and various clinical and pathologic features.

Overall, none of the 26 patients died of lymphoma. One patient died of a concomitant pancreatic carcinoma. Of the remaining 25 patients, 14 were disease free and 11 were alive with disease at a mean follow-up of 43 months. The estimated 5-year disease-free survival was 62%, and median disease-free survival was 69 months. The estimated 5-year relapse-free survival was 54%, and the median relapse-free survival was 63 months.

CD10 Expression in Primary Intestinal Large B-Cell Lymphomas.

Go JH, Yang WI, Ree HJ.

Department of Pathology, Dankook University College of Medicine, Cheonan-si, Chungchungnam-do, Korea (Dr Go); the Department of Pathology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea (Dr Yang); and the Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (Dr Ree).

Arch Pathol Lab Med 2002 Aug;126(8):956-960 Abstract quote

Objective.-To determine the prevalence and clinical significance of a follicular origin in primary intestinal large B-cell lymphomas.

Design.-We performed immunohistochemistry for detection of CD10 and Bcl-6 in paraffin-embedded tissue sections from 32 patients who had surgically resected primary intestinal lymphomas. We then correlated the expression of CD10 protein with various clinical parameters.

Results.-Fifteen of 32 cases (47%) were CD10(+), and CD10 positivity was correlated with intense Bcl-6 positivity. There were no significant differences in age, sex, serum lactate dehydrogenase level, and performance status between the CD10(+) and CD10(-) groups. Patients with CD10(+) lymphoma more frequently presented with stage I(2) disease compared with those with CD10(-) lymphoma (P =.03). The response to treatment was significantly better in the CD10(+) group than in the CD10(-) group (P =.02). An analysis of survival rates showed a trend for a longer overall survival duration in the CD10(+) group compared with the CD10(-) group, although this was not statistically significant (P =.05).

Conclusions.-We propose that more than half of primary intestinal large B-cell lymphomas have a germinal center cell origin. We also suggest that CD10 expression may be a prognostic indicator in patients with primary intestinal large B-cell lymphomas.

Lymphomas of the Female Genital Tract: A Study of 186 Cases and Review of the Literature.

Kosari F, Daneshbod Y, Parwaresch R, Krams M, Wacker HH.

From *Tehran University of Medical Sciences, Tehran, Iran; daggerUniversity of Miami School of Medicine, Miami, FL; and double daggerDepartment of Hematopathology, University of Kiel, and Lymph Node Registry, Kiel, Germany.

Am J Surg Pathol. 2005 Nov;29(11):1512-1520. Abstract quote  

Malignant lymphomas in the female genital tract are rare, and those arising from this tissue system are extremely uncommon. Most pertinent reports lack clear references to the accepted classifications or failed to apply immunomarkers and molecular techniques for a reliable diagnosis.

We analyzed a large group of patients with primary and secondary lymphomas of the female genital tract classified on the basis of the recent WHO consensus. A total of 186 patients with malignant lymphoma detected in the female genital tract were selected from the files of the Kiel Lymphoma Registry covering the period of 1974 to 2004. Stringent criteria were applied to separate systemic versus secondary lymphomas. All cases were reviewed on the basis of conventionally stained sections, relevant immunohistochemistry using the alkaline phosphatase/anti-alkaline phosphatase technique, and clinical information, as far as available. When required, gene rearrangement analysis was performed, including TCR-gamma chain gene and the three FR fragments of the IgG heavy chain gene. In addition, typical chromosomal translocations were detected by means of the FISH technique to verify the diagnosis, where needed. Thirty-seven percent of the cases were systemic lymphomas and 63% were mostly extranodal lymphomas primary to the female genital tract. The adnexa were involved in 87 cases, followed by uterine corpus in 23 cases, uterine cervix in 17 cases, portio in 9 cases, vagina in 11 cases, and vulva including clitoris in 8 cases. In 31 cases, two or more adjacent sites were involved. In both (primary and secondary) groups, the adnexa were the prevailing site of involvement. As expected, the overwhelming majority of cases were of B phenotype.

The most frequent type of lymphoma proved to be diffuse large B-cell lymphoma, closely followed by follicular lymphoma, including all 3 grades of malignancy. Burkitt lymphoma showed a rather similar frequency. Marginal zone lymphoma occurred exclusively as primary lesions in the uterine mucosa. Lymphoplasmacytic lymphoma was restricted to the vulvo-vaginal area and occurred in women over 60 years of age. In conclusion, our study provides a thorough overview of various types of lymphoma affecting the female genital tract primarily or secondarily, which were classified on the basis of a widely accepted WHO classification.

Although quite rare, our report should remind the pathologist of considering malignant lymphomas while reading biopsies taken from female genital organ.
Extranodal lymphomas of the head and neck.

Vega F, Lin P, Medeiros LJ.

Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.

Ann Diagn Pathol. 2005 Dec;9(6):340-50. Abstract quote  

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck and may involve nodal or extranodal sites. Nodal head and neck lymphomas are similar to other nodal sites and are not further reviewed here. The head and neck region is the second most frequent anatomical site of extranodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type. Hodgkin's lymphoma rarely occurs in extranodal sites. Other hematologic neoplasms that commonly involve extranodal sites of the head and neck are also discussed.
In this review, we begin by discussing lymphomas involving the head and neck according to anatomical site. Then we discuss specifically the pathological findings of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, plasmablastic lymphoma, extramedullary plasmacytoma, and extranodal natural killer/T-cell lymphoma of nasal type.
Primary Cardiac Lymphoma: Clinical, Histologic, Immunophenotypic, and Genotypic Features of 5 Cases of a Rare Disorder.

Department of Pathology, Brigham and Womenʼs Hospital and Harvard Medical School, Boston, MA.


Am J Surg Pathol. 2007 Sep;31(9):1344-1350. Abstract quote

Primary lymphomas of the heart are rare and frequently are diagnosed at autopsy. Modern imaging technology now permits early diagnosis and treatment.

This report describes the clinical, histologic, immunophenotypic, and molecular genetic findings for 5 patients with malignant lymphoma restricted to the cardiac muscle, with or without pericardial involvement. All patients were women, with ages ranging from 40 to 68 years (median 55 y). The right atrium was involved in all cases with the left atrium, right ventricle, and pericardium affected in 1 case each.

Clinical presentation included pericardial effusions associated with precordial pain, dyspnea, and bradycardia. Electrocardiographic changes included junctional rhythm, incomplete right bundle branch block and ST and T waves abnormalities, and ST segment elevation and first-degree atrioventricular block with intermittent complete heart block. In all cases, biopsy or resection of the lesion or cytologic examination of the pericardial fluid established a diagnosis. All tumors were of B-cell phenotype and included 4 cases of large cell lymphoma and one unclassifiable small cell lymphoma. In 2 cases, a follicular center cell origin was supported by reactivity of the neoplastic cells for CD10 and bcl-6 and by bcl-2 gene rearrangement by molecular analysis.

One patient died shortly after diagnosis due to cerebral infarction. Two patients are alive without disease after chemotherapy with CHOP after 120 and 192 months. One patient underwent chemotherapy with CHOP and rituximab, and shows persistent cardiac involvement by lymphoma but with a decrease in tumor burden at 7 months of follow-up. One patient was lost to follow-up. Clinical outcome is variable; however, early diagnosis in conjunction with effective treatment (surgery and/or chemotherapy) may result in an excellent prognosis.

Primary cardiac lymphoma should be included in the differential diagnosis of a right atrial mass.

Lymphomas of the oral cavity: Histology, immunologic type, and incidence of Epstein-Barr virus infection.

Solomides CC, Miller AS, Christman RA, Talwar J, Simpkins H.

Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA.

Hum Pathol 2002 Feb;33(2):153-7 Abstract quote

The purpose of this study was to determine the histologic class and immunologic phenotype of lymphomas presenting initially in the oral cavity and whether this correlated to a high incidence of Epstein-Barr virus (EBV) infection as has been reported with lymphomas in the nasal cavity.

Seventy-one cases of oral lymphomas from the oral pathology referral service were analyzed retrospectively. They were classified according to the Revised European American Lymphoma (REAL) classification system using routine immunohistochemistry. EBV infection was determined by detection of early viral RNA sequences (EBER) and latent membrane protein (LMP-1) expression.

Only non-Hodgkin's lymphomas were observed, with a female predominance of 2:1. They were primarily of B-cell origin and histologically classified mainly as large B-cell type (68%); T-cell lymphomas were rare (8%). EBV infection was observed in 14% of the B-cell lymphomas, an incidence rate higher than that reported in studies of B-cell lymphomas not located in the oral cavity but not as high as that observed in pleomorphic T-cell lymphomas (all sites, 36%) or nasal cavity T-cell lymphomas (nearly 100%). Interestingly, EBV proliferation did not correlate with expression of either Bcl-2 or p53.

Primary Pancreatic Lymphoma Evaluated by Fine-Needle Aspiration
Findings in 14 Cases

Keith E. Volmar, MD, Mark J. Routbort, MD, PhD, Claudia K. Jones, MD, and H. Bill Xie, MD, PhD
Am J Clin Pathol 2004;121:898-903 Abstract quote

Fine-needle aspiration (FNA) is a popular method for evaluating pancreatic lesions. There is considerable literature on FNA evaluation of primary pancreatic carcinomas, but few studies address the FNA diagnosis of primary pancreatic lymphoma.

We reviewed 14 cases of atypical lymphoid processes diagnosed by FNA during a 5-year period, constituting 1.3% of a total of 1,050 pancreatic FNA cases. The diagnoses were as follows: 6 large B-cell lymphomas, 4 follicular lymphomas, 3 suggestive of lymphoma, and 1 unclassified B-cell lymphoma. Lymphoid neoplasms manifested in older people (mean age, 64.7 years) as a solitary mass in the pancreatic head, mimicking primary carcinoma. Clonality was confirmed by flow cytometry in 11 cases and immunohistochemical analysis on cell block material in 2. Obtaining diagnostic material often required several passes (average, 3.9 passes; range, 1-8 passes).

We conclude that primary pancreatic lymphomas rarely are diagnosed by FNA, tend to be high grade, and clinically and radiographically might mimic primary carcinoma.

Primary Lymphoma of Peripheral Nerve Report of Four Cases

Joseph Misdraji, M.D.; Yasushi Ino, M.D.; David N. Louis, M.D.; Andrew E. Rosenberg, M.D.; E. Antonio Chiocca, M.D., Ph.D.; Nancy L. Harris, M.D. Spencer PS, Schaumburg HH, eds.

From the James Homer Wright Pathology Laboratories of Massachusetts General Hospital and Department of Pathology (J.M., Y.I., D.N.L., A.E.R., N.L.H.), Harvard Medical School; and the Neurosurgery Service of Massachusetts General Hospital (Y.I., D.N.L., E.A.C.), Boston, Massachusetts, U.S.A.

Am J Surg Pathol 2000;24:1257-1265 Abstract quote

Lymphoma presenting as a solitary tumor of peripheral nerve is exceedingly rare, with only six previously reported cases. The authors describe an additional four cases of primary lymphoma of peripheral nerve involving the sciatic nerve (two cases), the radial nerve, and the sympathetic chain and spinal nerve.

The patients were two men and two women with an average age of 55.5 years. All tumors were high-grade B-cell lymphomas. Two patients experienced relapse of disease with involvement of other nervous system sites and died of lymphoma. One patient is alive with stable local disease at 57 months. The fourth patient is alive with no evidence of disease at 54 months. Expression of neural cell adhesion molecule (CD56) has been reported to correlate with an increased incidence of central nervous system involvement in peripheral T-cell lymphoma; all their cases were CD56 negative. Recent reports indicate a high proportion of primary brain lymphomas show loss of CDKN2A/p16 gene expression. Therefore, CDKN2A/p16 was evaluated in their patients both by polymerase chain reaction and by immunohistochemistry for the p16 protein. The authors found homozygous deletion of the CDKN2A/p16 gene in one of three patients studied, confirmed immunohistochemically by absent staining for p16. The fourth patient showed absent staining for p16, suggesting inactivation of the gene in this case as well. The two patients with p16 loss both died of lymphoma, whereas the two patients with normal p16 expression are alive.

Primary lymphoma of peripheral nerve is a rare neoplasm, usually of large B-cell type, has a variable prognosis, and appears to have less consistent loss of p16 expression than primary central nervous system lymphoma.


Pyothorax-associated lymphoma: a review of 106 cases.

Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa K.

Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan.

J Clin Oncol 2002 Oct 15;20(20):4255-60 Abstract quote

PURPOSE: Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity after a long-standing history of pyothorax. Full details of PAL are provided here.

PATIENTS AND METHODS: Clinical and pathologic findings were reviewed in 106 patients with PAL collected through a nationwide survey in Japan.

RESULTS: Age of the patients with PAL was 46 to 82 years (median, 64 years), with a male/female ratio of 12.3:1. All patients had a 20- to 64-year (median, 37-year) history of pyothorax resulting from artificial pneumothorax for treatment of pulmonary tuberculosis (80%) or tuberculous pleuritis (17%). The most common symptoms on admission were chest and/or back pain (57%) and fever (43%). Laboratory data showed that the serum neuron-specific enolase level was occasionally elevated (3.55 to 168.7 ng/mL; median, 18.65 ng/mL), suggesting a possible diagnosis of small-cell lung cancer. Histologically, PAL usually showed a diffuse proliferation of large cells of B-cell type (88%). In situ hybridization study showed that PAL in 70% of the patients was Epstein-Barr virus (EBV)-positive. PAL was responsive to chemotherapy, but the overall prognosis was poor, with a 5-year survival of 21.6%.

CONCLUSION: This study established the distinct nature of PAL as a disease entity. PAL is a non-Hodgkin's lymphoma of exclusively B-cell phenotype in the pleural cavity of patients with long-standing history of pyothorax, and is strongly associated with EBV infection. Development of PAL is closely related to antecedent chronic inflammatory condition; therefore, PAL should be defined as malignant lymphoma developing in chronic inflammation.


Ovarian Non-Hodgkin’s Lymphoma: A Clinicopathologic Study of Eight Primary Cases

Russell Vang, M.D., L. Jeffrey Medeiros, M.D., Roger A. Warnke, M.D., John P. Higgins, M.D. and Michael T. Deavers, M.D.

Stanford University Medical Center (RV, RAW, JPH), Department of Pathology (Laboratory of Surgical Pathology), Stanford, California; and The University of Texas-M.D. Anderson Cancer Center (JM, MTD), Houston, Texas

Mod Pathol 2001;14:1093-1099 Abstract quote

Primary (localized) non-Hodgkin’s lymphoma (NHL) of the ovary is rare.

We studied eight cases of primary ovarian NHL to better understand the clinicopathologic and immunophenotypic features of these tumors. The patients ranged in age from 29 to 62 years (mean 47 years). Pelvic complaints were the most common symptoms; however, three of eight neoplasms were discovered incidentally. All tumors were unilateral and Ann Arbor stage IE. The three incidental NHL were microscopic (largest 1.2 cm), whereas the grossly evident lesions ranged from 7.5 to 20 cm (mean 13.3).

Each tumor was classified according to the World Health Organization Classification as follows: diffuse large B-cell lymphoma (three cases), follicular lymphoma (two cases), Burkitt lymphoma (one case), T-cell anaplastic large cell lymphoma (one case), and precursor T-lymphoblastic lymphoma (one case). Six tumors were of B-cell lineage, and two tumors were of T-cell lineage. All three diffuse large B-cell lymphomas were positive for BCL-6, two were positive for CD10, and two were positive for BCL-2. Estrogen and progesterone receptors were negative in all NHLs assessed. Patients were treated by various combinations of surgery, chemotherapy, and radiotherapy. Clinical follow-up ranged from 1.3 to 11.7 years (mean 5.2) and all patients were alive without disease at last follow-up.

We conclude that most patients with primary ovarian NHL present with symptoms attributable to an ovarian mass, but in a subset of patients ovarian NHL may be detected incidentally. With appropriate therapy, patients appear to have a favorable prognosis although follow-up is short for some patients in this study.


Excessive survivin expression in thyroid lymphomas.

Sugawara M, Matsuzuka F, Fukata S, Kuma K, Moatamed F, Haugen BR.

Division of Endocrinology and Metabolism, Molecular Pathology Division, Department of Pathology and Laboratory Medicine, Greater Los Angeles Veteran's Affairs Medical Center and UCLA School of Medicine, 90073, USA.

Hum Pathol 2002 May;33(5):524-7 Abstract quote

Thyroid lymphoma occurs most commonly in the thyroid glands with a background of Hashimoto's thyroiditis. Therefore, it is occasionally difficult to distinguish lymphoma from Hashimoto's thyroiditis because of some cellular and histologic similarities.

We have examined whether survivin or human telomerase reverse transcriptase (hTERT) expression can differentiate between the 2 disorders. Surgically removed tissue samples from 6 patients with thyroid lymphoma and 6 patients with Hashimoto's thyroiditis were analyzed for mRNA levels of survivin and hTERT by real-time quantitative reverse-transcription polymerase chain reaction. Expression of survivin protein was examined by immunohistochemical stain using a polyclonal antibody. Survivin mRNA levels were greater in thyroid lymphoma than in Hashimoto's thyroiditis: 49.1 +/-36.4 versus 6.6 +/-2.7 pg/ng rRNA (mean +/- SD) (P <0.005). Immunohistochemical stain confirmed an abundance of survivin protein in lymphoid cells of thyroid lymphoma. The amount of hTERT mRNA did not differ in the 2 disorders.

Our study shows that measuring survivin mRNA levels or immunohistochemistry of the protein expression can be useful to aid the diagnosis of thyroid lymphoma when histologic diagnosis is difficult.


Focal follicular features in tonsillar diffuse large B-cell lymphomas: follicular lymphoma with diffuse areas or follicular colonization.

Ree HJ, Kikuchi M, Lee SS, Ohshima K, Yang WI, Ko YH, Cho EY, Rhee JC.

Department of Diagnostic Pathology, Samsung Medical Center, Seoul, Korea.

Hum Pathol 2002 Jul;33(7):732-40 Abstract quote

Focal follicular features in diffuse large B-cell lymphomas (DLBCLs) are bound to raise the question of follicular lymphoma (FL) with diffuse areas, because the diagnosis of FL is based on the presence of follicular areas, even though focal.

We report 7 cases of primary tonsillar DLBCLs with focal follicular features that presented with morphologic, immunohistochemical, and biological features distinct from those of FL. Histologically, these tumors were characterized by involvement of pericryptal follicles with adjacent dominant diffuse areas. Monomorphous large tumor cells were evenly spaced with abundant, often clear cytoplasm, and blastoid nuclei often with a delicate nuclear membrane. Importantly, residual germinal centers (GCs) were present in the form of either an intrafollicular GC remnant or an isolated GC in the midst of diffuse tumor. An extrafollicular and/or parafollicular growth pattern was also observed. Bcl-6 staining revealed a predominantly sporadic occurrence of Bcl-6(+) cells, comprising <50% of tumor cells, and none displayed diffusely dense collections (>75%) of Bcl-6(+) tumor cells characteristic of the GC or FL. Staining for CD10 was negative in 6 cases. Five of 7 patients were younger than 60, the median age of other patients with primary tonsillar DLBCL.

No extratonsillar involvement was seen at 18 months after diagnosis. After chemotherapy or radiotherapy, complete remission was achieved with ease in all patients, but 2 patients who were treated with chemotherapy alone relapsed at 24 and 30 months. In conclusion, tonsillar DLBCL includes a small (10%) but distinct subgroup that warrants distinction from FL with predominant diffuse areas or de novo DLBCL.

It appears that the focal follicular features in tonsillar DLBCL likely represent follicular colonization of marginal zone B-cell lymphoma, probably high-grade, if the possibility of FL is excluded.

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