Secondary non-Hodgkin Lymphoma Research Articles

Pathology review identifies frequent misdiagnoses in recurrent classic Hodgkin lymphoma in a nationwide cohort: implications for clinical and epidemiological studies.

Patients treated for classic Hodgkin lymphoma (CHL) have a reported 13-fold increased risk of developing subsequent non-Hodgkin lymphoma (NHL). In light of the growing awareness of CHL mimickers, this study re-assesses this risk based on an in-depth pathology review of a nationwide cohort of patients diagnosed with CHL in the Netherlands (2006-2013) and explores the spectrum of CHL mimickers. Among 2,669 patients with biopsy-proven CHL, 54 were registered with secondary NHL. On review, CHL was confirmed in 25/54 patients. In six of these, the subsequent lymphoma was a primary mediastinal B-cell lymphoma/mediastinal gray zone lymphoma, biologically related to CHL and 19/25 were apparently unrelated B-cell NHL. In 29/54 patients, CHL was reclassified as NHL, including T-cell lymphomas with secondary Hodgkin-like B-blasts (n=15), Epstein Barr virus-positive diffuse large B-cell lymphoma (n=8), CD30+ T-cell lymphoma (n=3) and indolent B-cell proliferations (n=3). Higher age, disseminated disease at presentation, extensive B-cell marker expression and association with Epstein-Barr virus were identified as markers to alert for CHL mimickers. Based on these data, the risk of developing NHL after CHL treatment was re-calculated to 3.6-fold (standardized incidence ratio 3.61; confidence interval: 2.29-5.42). In addition, this study highlights the clinicopathological pitfalls leading to misinterpretation of CHL and consequences for the care of individual patients, interpretation of trials and epidemiological assessments.

CML-357 Jumping Out of the Frying Pan, Into the Fire: Case Report of Secondary Non-Hodgkin Lymphoma (NHL) in a Case of Chronic Myeloid Leukemia (CML)

The introduction of TKIs at the start of the second millennium has dramatically changed CML treatment. Now, two decades later, we are observing and trying to assess the long-term side effects of prolonged TKI use. To report a secondary malignancy in a CML patient on TKI and its impact on her CML course. This is a case report of a chronic-phase CML patient who developed NHL. OCMU is an academic institutional practice acting as a referral center that provides multidisciplinary tertiary care for hematology patients in the Egyptian delta region. A 58-year-old female resident of Damietta was referred to OCMU in January 2020 after discovering leukocytosis. She was diagnosed as CML based on blood film, bone marrow aspiration, and biopsy results and was confirmed by the detection of Philadelphia chromosome P210 in 46% of cells. The patient was started on 100 mg dasatinib, but she developed a diffuse skin rash with recurring anemia requiring transfusion and dasatinib interruptions. She was shifted to nilotinib with the absence of the previous toxicities and QPCR reduction. She was referred back to us in November 2021 with left submandibular swelling measuring 3.8×3.5 cm, with submandibular LNs as large as 1.8×1.1 cm with faint hilum. QPCR was undetectable, but bone marrow aspiration and both free-hand and tru-cut biopsies revealed DLBCNHL positive for CD20 and negative for CD3 and CD23, with Ki67 detected in 85%. CD34, CD117, and TdT were negative, excluding chloroma. PET-CT showed active uptake only in the submandibular mass (4 × 3 cm; SUV=7). She started the R-CHOP regimen and continued nilotinib. The response was assessed by PET-CT and QPCR. PET- CT was negative after four cycles, and QPCR remained undetectable. Therefore, the patient is continuing nilotinib with regular monthly follow-up for lymph node ultrasonography. Secondary malignancies with CML are increasingly common, but the literature reports contradictory data, with NHL ranked as the fourth most common secondary malignancy. The roles of TKIs in disease evolution and increased life expectancy require more research to assess the genetic bases and incidences of secondary malignancies.

Detection of Non-Hodgkin Lymphoma Within Ovarian Tissue.

This case report describes the detection of non-Hodgkin lymphoma (NHL) within ovarian tissue after cryopreservation. The 27-year-old woman presented no gynecological symptoms such as pelvic pain or abnormal uterine bleeding. During laparoscopy for ovarian tissue cryopreservation, the ovaries appeared markedly modified and some solid content cysts were highlighted. Microscopically the cysts revealed the presence of lymphoid infiltrate, whereas the histological assessment of some fragments of the ovarian cortical tissue revealed no evidence of pathological lymphoid infiltration. This case report describes the presence of pathological lymphoid infiltration in ovarian cysts but not in the cortical tissue of a young woman with secondary NHL. Despite the absence of the positivity in cortical tissue it was recommended to avoid the cryopreserved ovarian tissue transplantation to reduce the risk of reseeding of the malignancy in the woman.

Characterization of Second Primary Malignancies in Mucosa-Associated Lymphoid Tissue Lymphomas: A SEER Database Interrogation.

Introduction: Second primary malignancies (SPMs) are long-term complications in cancer survivors. Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent extra-nodal marginal zone lymphomas, the majority of which typically have long-term survival. In this study, we investigated the incidence and pattern of SPMs in adult patients diagnosed with MALT lymphomas between January 2000 and December 2016. Methods: Using the SEER-18 database and multiple primary standardized incidence ratio (MP-SIR) session of SEER stat software for statistical analysis, we assessed SPMs in MALT lymphomas. Results: During this time, a total of 12,500 cases of MALT lymphomas were diagnosed, of which 1466 patients developed 1626 SPMs (O/E ratio: 1.48, 95% CI:1.41-1.55, P<.001). The median latency period for development of SPMs was 54 months (range 6-201 months). Secondary non-Hodgkin lymphomas, as defined by SEER as distinct from the primary lymphoma, was the most common SPM with 299 cases, followed by lung cancer (O/E ratio: 6.15, 95% CI:5.47-6.89, P<.0001). There were 898 SPMs that developed between 6- 59 months (O/E ratio: 1.47, 95% CI:1.37-1.57, P<.0001) and 728 after 60 months latency (O/E ratio: 1.5, 95% CI:1.39-1.61, P<.0001) after diagnosis of the primary MALT lymphomas. An increased incidence of both solid and hematologic cancers occurred in patients as early as 6 months after diagnosis of MALT lymphoma. Conclusion: These findings indicate that despite the indolent nature of most MALT lymphomas, there is an increased risk for SPMs warranting long-term follow up.

Secondary Haematological Cancers in Adults: A Single Centre Experience

Introduction: Advances in early detection and treatment mean that more and more people are surviving cancer today. Increased long-term survival seen in patients with solid and hematologic cancers achieved as a result of aggressive chemo radiotherapy has come at a price. Some cancer survivors may develop a new, unrelated cancer later. This is called a second cancer. Reasons for second cancers are varied. Field cancerization, shared environment, familial syndromes, Radiation and Chemotherapy are among the few risk factors affecting the risk of secondary cancers. Therapy-related acute myeloid leukaemia and secondary non-Hodgkin lymphoma has been frequently documented in these patient cohorts. We aim to study the prevalence as well as analyse the factors involved in secondary haematological cancers in our subset of patients.Methods: This Cross sectional descriptive study was taken up in Apollo Institute of Medical Sciences and Research, Hyderabad. This is a 5 year observational study. We analysed all patients presenting to the Department of pathology, Apollo Hospitals during the period 2010 to 2015.Results: Total 4 cases of Second cancers were documented in our study. Out of which 2 cases were acute myeloid leukaemias and both of them had history of treatment with alkylating agents. The other 2 cases were diagnosed to have secondary Multiple myeloma. Of the patient presenting with multiple myeloma one of them had history of prior Renal cell carcinoma Conclusion: Assessment of the risk of second leukaemia should become part of any therapeutic plan for cancer patients. Chemo is known to be a greater risk factor then radiation. Avoidance of drugs with more leukemogenic potential will reduce the occurrence of second leukaemias. It is also important to understand the possibility of a correlation between renal cell carcinoma and multiple myeloma. Field cancerization and increased cytokine expression probably could play an important role in these second cancers. DOI: 10.21276/APALM.1531

Second Primary Malignancies in CTCL Patients from 1992 to 2011: A SEER-Based, Population-Based Study Evaluating Time from CTCL Diagnosis, Age, Sex, Stage, and CD30+ Subtype.

Cutaneous T-cell lymphoma (CTCL) is a diverse group of extranodal non-Hodgkin lymphomas with malignant T lymphocytes localizing in the skin. CTCL can mainly be classified as mycosis fungoides, Sézary syndrome, or primary cutaneous CD30+ lymphoma. Patients with CTCL have an increased risk of developing second primary malignancies. Our objective was to analyze the overall incidence of second primary malignancies in patients with CTCL by age, sex, stage, and the primary cutaneous CD30+ lymphoproliferative subtype of CTCL, as this group has usually been excluded from previous analyses. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate CTCL cases diagnosed between 1992 and 2011. We calculated the multiple primary standardized incidence ratio, comparing the observed incidence of second primary malignant neoplasms in the CTCL patient population versus the general population. CTCL is associated with an overall increased risk of cancers. This incidence is greatest within the first year of diagnosis. The risk of secondary Hodgkin disease is greatest in patients aged ≥60 years; the risk of secondary non-Hodgkin lymphoma is greatest in patients aged 20-39. Males demonstrated a significantly increased risk of developing Hodgkin lymphoma, while females showed a significantly increased risk of developing bronchopulmonary malignancy. Overall, secondary malignancy incidence was significantly elevated for stage I and IV CTCL. Patients with CD30+ CTCL had a significantly higher incidence of Hodgkin lymphoma, non-Hodgkin lymphoma, and urinary cancers than the general population. Occult secondary malignancies, particularly lymphomas, should be considered in adult CTCL patients, including those with the CD30+ subtype.

Epstein–Barr virus-positive diffuse large B-cell lymphoma following acute myeloid leukemia: a common clonal origin indicated by chromosomal translocation t(3;4)(p25;q21)

Secondary non-Hodgkin lymphoma following acute myeloid leukemia (AML) is extremely rare. We here describe a unique case involving a patient who developed Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) during complete remission (CR) of AML. A 75-year-old Japanese man was initially diagnosed with AML with maturation (FAB M2), bearing chromosomal translocation t(3,4)(p25;q21). After intensive chemotherapy, bone marrow aspiration revealed normal karyotype, and he achieved CR. Six years and 4 months later, he was still in CR from AML, but developed DLBCL presenting in the terminal ileum. Cytogenetic analysis of the DLBCL cells showed the same translocation as the previous AML. The rearrangements of the immunoglobulin heavy chain genes of the two malignancies were examined using polymerase chain reaction amplification, and the rearrangement patterns were found to differ from each other. Our data thus suggest that, in the present case, the AML and DLBCL arose from a common progenitor cell, as indicated by the clonal abnormality t(3,4)(p25;q21), and that different immunoglobulin heavy chain gene rearrangements occurred during each course of clonal evolution.

Disparate survival and risk of secondary non-Hodgkin lymphoma in histologic subtypes of Hodgkin lymphoma: a population-based study

We compared survival outcomes and rates of secondary non-Hodgkin lymphoma (NHL) in 28 323 patients with nodular lymphocyte predominant (NLPHL) and classical Hodgkin lymphoma (HL) from the Surveillance, Epidemiology and End Results database, diagnosed between 1995 and 2010. In a multivariate analysis NLPHL demonstrated a significantly better relative survival (5-year risk of lymphoma-related death 5.7%, hazard ratio [HR] 0.46, p < 0.0001) than the reference nodular sclerosis (NSHL) subtype (5-year risk 12.7%). Lymphocyte-rich classical HL had outcomes comparable to NSHL (5-year risk 14.3%, HR 0.84, p = 0.11). Exceptionally poor outcomes were observed in lymphocyte depleted HL (5-year risk 48.8%, HR 2.26, p < 0.0001). The risk of secondary NHL was increased in NLPHL (HR 2.81, p < 0.001) and lymphocyte-rich classical HL (HR 2.27, p = 0.002), but not in other subtypes compared with NSHL. In conclusion, the histologic classification retains a significant prognostic value in HL and the disparities between the subtypes warrant customized treatment and surveillance strategies.

Risk and outcome of non‐Hodgkin lymphoma among classical Hodgkin lymphoma survivors

Survivors of classical Hodgkin lymphoma (cHL) are at an increased risk of developing secondary non-Hodgkin lymphomas (sNHLs). To the authors' knowledge, the outcome of patients with sNHL compared with their de novo counterparts (dnNHL) is unknown. Data from 26,826 cases of HL from the Surveillance, Epidemiology, and End Results (SEER) program that were diagnosed between 1992 and 2009 were used to obtain the risk of further development of different subtypes of sNHL. The survival of patients with sNHL was compared with that of matched patients with dnNHL. The estimated cumulative incidence of sNHL was 2.50% (95% confidence interval [95% CI], 2.10-2.89) at 15 years from the diagnosis of cHL. The standardized incidence ratio was 10.5 (95% CI, 8.9-12.4) for aggressive B-cell NHL, 4.0 (95% CI, 3.1-5.1) for indolent B-cell NHL, and 14.6 (95% CI, 10.3-20.1) for T-cell NHL. Patients with indolent B-cell sNHL had a worse overall survival compared with their dnNHL counterparts (hazards ratio [HR] of death, 2.7; 95% CI, 1.3-5.7). Survival was not significantly different between patients with sNHL and those with dnNHL with regard to aggressive B-cell NHL (HR, 1.3; 95% CI, 0.6-2.7) or T-cell NHL (HR, 0.8; 95% CI, 0.3-1.8). The risk of developing sNHL after cHL is substantial. Although patients with indolent B-cell sNHL have inferior survival, patients with aggressive B-cell sNHL and T-cell sNHL have survival comparable to that of their de novo counterparts.

Nodular lymphocyte-predominant and classical Hodgkin lymphoma subtypes: Differences in biology, survival, and impact of radiotherapy.

8550 Background: Hodgkin lymphoma (HL) is a heterogeneous disease, but differences between nodular lymphocyte predominant (NLPHL) and classical (CHL) subtypes were previously studied in small cohorts preventing adjustment for confounders. We studied those differences based on the Surveillance, Epidemiology and End Results (SEER) program data. Methods: We analyzed SEER HL cases aged 16 years and over, diagnosed between 1995 and 2009. We studied the following endpoints: crude probability of HL-related death (HLRD), relative survival (using individual data in multivariate flexible parametric models) and risk of secondary malignancies (using competing risk regression). We studied the impact of radiotherapy (RT) in early-stage disease using a propensity score, adjusting for treatment selection and immortal time bias. Results: We identified 25,903 patients, with disparate age, race and stage distributions between subtypes. In a multivariate model, NLPHL demonstrated significantly better crude and net survival outcomes (Table), but in contrast to all CHL subtypes, it showed a steady increase in mortality rate after 2 years. The risk of secondary non-Hodgkin lymphoma was significantly higher in both NLPHL (hazard ratio, HR, 2.28, P=0.002) and lymphocyte-rich (LR) CHL (HR 2.08, P=0.01) than in nodular sclerosis (NS). The risk of other secondary malignancies did not differ between subtypes. After balancing confounding factors in treatment arms, RT in stage I/II was associated with improved survival in NS (HR, 0.78, P=0.001) and LR-CHL (HR 0.36, P&lt;0.001), but not in NLPHL (HR 0.98, P=0.94) or in the remaining CHL subtypes. Conclusions: Studies of NLPHL and CHL subtypes should account for their disparate biology and clinical course. Prospective evaluation of NLPHL treatment strategies without RT is justified. [Table: see text]

Risk and Outcome of Non-Hodgkin Lymphoma Among Hodgkin Lymphoma Survivors: Analysis From the Surveillance, Epidemiology and End Results (SEER) Registry.

Abstract 2639 Background:A variety of secondary malignancies have been observed among patients treated for Hodgkin lymphoma (HL) including non-Hodgkin lymphomas (NHL). Data on risk of developing NHL after therapy for HL is limited. The management of patients with secondary (after HL) NHL (sNHL) may be challenging due to the cumulated toxicity from HL treatment. The outcome of patients with s NHL relative to their de novo counterparts (dn NHL) is unknown. Methods:We used data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER-18) to determine the incidence and long term overall survival (OS) of patients with secondary NHL (sNHL) after HL therapy. Inclusion criterion was diagnosis of HL in the period of 1992–2009 as first malignant neoplasm. To avoid inclusion of patients with concomitant HL and NHL diagnosis, cases with the two distinct histologies reported up to 3 months apart as well as patients with HL and less than 3 months of follow up were excluded from the analysis. Follow up was updated up to the end of 2009 (November 2011 submission). Cumulative incidence of sNHL among HL survivors was calculated using a competing risk model, treating death from any cause in absence of sNHL as the competing risk. In order to compare outcomes of sNHL with dnNHL, we matched dnNHL to sNHL cases in a 2:1 ratio based on the following parameters in decreasing priority: histological subtype, stage, calendar year of diagnosis, age, race, gender, and SEER registry. A Cox proportional hazard model with normal frailty was used to compare OS of sNHL cases to the dnNHL cases. Results:A total of 26,826 HL cases were included in the analysis with median follow up of 62 months (range 3–215). Median age of patients was 34 years (range 2–99), 8324 (31.0%) had advanced stage, 14619 (54.5%) had limited stage and stage was unknown for 3883 (14.5%) patients. The cumulative incidence of sNHL was 0.41% (95% C.I. 0.32–0.50), 1.34% (95% C.I. 1.41–1.55) and 2.50% (95% C.I. 2.10–2.89) 5 years, 10 years and 15 years after the diagnosis of HL respectively. Incidence of sNHL was closely linked to age at diagnosis of HL. Cumulative incidence at 15 years post HL diagnosis was 0.67% (95% C.I. 0.04–1.29) for age <20 years, 2.23% (95% C.I. 1.77–2.67) for age 20–59 years and 5.59% (95% C.I. 4.21–6.97) for age 60 or older (p<0.001, Figure 1). Overall, 259 cases of sNHL were diagnosed. Most patients with sNHL were males (62.2%) and white (84.6%). The median age at the diagnosis of sNHL was 56 years (range 10–92). Thirty eight (14.7%) sNHL were T-cell lymphomas, 144 (55.6%) aggressive B-NHL, 64 (24.7%) indolent B-NHL and 13 (5%) were not classified. Patients with sNHL had worse OS than their dnNHL counterparts for indolent B-NHL (HR of death 2.7, 95% CI 1.3–5.7, p=0.008) but not for aggressive B-NHL (HR 1.3, 95% C.I. 0.6–2.7, p=0.19) or T-NHL (HR 0.8, 95% C.I 0.3–1.8, p=0.42). Overall survival per histological group is displayed in Figure 2. Conclusion:The risk of developing sNHL after therapy for HL is substantial, particularly among older patients. The OS for patients with indolent B-cell sNHL is inferior to their matched dnNHL counterpart. Such difference in outcome could not be verified for aggressive B-cell and T-cell sNHL [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Secondary non-Hodgkin lymphoma (NHL) in children and adolescents after childhood cancer other than NHL

The emergence of non-Hodgkin lymphoma (NHL) during childhood and adolescence as a secondary neoplasm (SN) after previous cancer other than NHL is rare. To describe the characteristics and outcome of NHL following previous cancer other than NHL in children and adolescents, this study analysed the data of patients reported to the NHL-Berlin-Frankfurt-Münster study centre from 1986 to 2005. Out of the total of 2968 NHL-patients registered, 11 patients were assessed as having suffered from NHL as a proven SN. Four additional children had most likely suffered from NHL as an SN, but a late relapse of the first neoplasm could not be ruled out unequivocally. In the patients with proven SN, median age at diagnosis of the primary malignancy was 3.9 years (range 2-11.7). The median age at diagnosis of NHL was 7.6 years (range 4.7-18). Only lymphoblastic (n = 7) and diffuse large B-cell (n = 4) lymphomas were diagnosed as SN. The estimated 5-year event-free survival from time of diagnosis of NHL was 91% [95% confidence interval (CI) 74-100%] in patients with proven SNs and 84% (95% CI 63-100%) when the patients with probable SNs were included in the analysis. We concluded that secondary NHL in children and adolescents confers a favourable prognosis.

Non-Hodgkin Lymphoma Secondary to Cancer Chemotherapy

Increased long-term survival seen in patients with solid and hematologic cancers achieved as a result of aggressive chemoradiotherapy has come at a price. Therapy-related acute myeloid leukemia has been frequently documented in these patient cohorts, and its biology well studied. Recognition of secondary non-Hodgkin lymphoma as a cause of significant morbidity and mortality in these patients is equally important. The patterns of incidence and latency of secondary lymphomas is distinct from that of myeloid malignancies and other solid cancers. We have systematically analyzed and summarized reports from various groups over the last three decades. Risk of secondary lymphomas increases after the first 5 years of completion of chemotherapy or radiotherapy and persists for more than three decades. This reinforces the need for long-term follow-up of all patients exposed to chemoradiotherapy and confirms that chemotherapeutic agents can cause lymphoma.

Non-Hodgkin's Lymphoma of the Nasopharynx: CT and MR Imaging

OBJECTIVE: Nasopharyngeal (NP) non-Hodgkin's lymphoma (NHL) is an uncommon tumour. The aim of the study was to describe the appearances on CT and MR imaging, and identify the features which help to distinguish NPNHL from other NP tumours. MATERIALS AND METHODS: The CT ( n=8) and MR ( n=10) images of 14 patients with NPNHL were reviewed retrospectively. Patients with NPNHL were divided into primary NPNHL, where the primary tumour was in the NP ( n=7) and secondary NPNHL where the primary tumour was at another extranodal site in the head and neck ( n=7). All NPNHL were assessed for tumour size and distribution, appearance and local tumour invasion, in addition lymphadenopathy was assessed in primary NPNHL. RESULTS: The NPNHL ranged in size from 20–75 mm (mean of 55 mm for primary and 30 mm for secondary NHL) and were homogeneous on CT in eight (100%) and MR in seven (70%) and mildly heterogeneous on MR in three (30%) patients. NPNHL involved all walls of the NP in 10 (71%) and extended in an exophytic fashion to fill the NP cavity in six (43%). Deep tumour invasion was present in two (14%) both patients with primary NHL, the extent and volume of this tumour invasion was small and involved the prevertebral muscles ( n=2), parapharyngeal fat space ( n=1) and skull base ( n=1). Primary NPNHL extended superficially in five (71%) to involve the nasal cavity ( n=3) and oropharynx ( n=2) and lymphadenopathy was present in five (71%) being bilateral and involving multiple nodal sites ( n=4) with necrosis ( n=2) and matting ( n=3). CONCLUSION: NPNHL is a homogeneous tumour that tends to diffusely involve all walls of the nasopharynx and spread in an exophytic fashion to fill the airway, rather than infiltrating into the deep tissues. Deep tumour infiltration, when it occurs, is found in those patients with primary NHL and is usually limited in extent and of small volume. Primary NHL more commonly spreads superficially to involve the nasal cavity or oropharynx, lymphadenopathy is frequent and extensive. A large tumour that fills the nasopharynx, with no or minimal invasion into deep structures, and a propensity to extend down into the tonsil, rather than up into the skull base, may suggest the diagnosis of NHL over nasopharyngeal carcinoma.

A Novel B-cell Line (U-2932) Established from a Patient with Diffuse Large B-cell Lymphoma Following Hodgkin Lymphoma

Little is known about mechanisms leading to secondary non-Hodgkin lymphomas (NHL) in patients treated for Hodgkin lymphoma (HL). Our aim was to characterise in detail a cell line derived from a diffuse large B-cell lymphoma (DLBCL) that had developed in a patient with relapsing HL. The cell line U-2932 was established from ascites in a patient suffering from DLBCL previously treated for HL with multiple chemotherapy regimens. Characterisation was based on morphology, immunophenotype, Epstein-Barr virus (EBV)-status, IgH gene rearrangement status, tumourigenicity, p53 sequencing, and immunohistochemical expression of p53, BCL-2 and BCL-6. The karyotype was investigated using G-banding, comparative genomic hybridisation (CGH) and spectral karyotype (SKY) analysis. This cell line shows typical morphological features of a DLBCL and grows as colonies in nude mice. It expresses a B-cell phenotype with a somatically hypermutated V H 4-39 gene and is negative for EBV. The origin of U-2932 was confirmed by demonstrating an identical V H 4 rearrangement in ascites from the patient. A point mutation of the tumour-suppressor gene p53 was detected in amino acid position 176 and immunohistochemical over-expression of the p53 protein was also demonstrated. U-2932 carries a complex karyotype including high-level amplifications of the chromosomal bands 18q21 and 3q27 and expresses aberrant BCL-2 and BCL-6 immunohistochemically. We were unable to investigate the clonal relationship between the original HL and U-2932. In conclusion, U-2932 is a unique B cell line established from a patient suffering from HL followed by NHL. Overexpression of BCL-2, BCL-6 and p53 may play a role in the tumourigenesis and drug resistance. This cell line may become a useful tool to better understand the mechanisms responsible for development of secondary NHL in patients treated for HL.

Malignant hematopoietic breast tumors.

Hematopoietic neoplasms involving the breast, although less common than breast carcinoma, are often clinically indistinguishable from other breast tumors. Microscopically, these tumors can mimic primary carcinoma of the breast, especially in limited material such as needle biopsy specimens. Forty-five hematopoietic breast neoplasms including 21 primary non-Hodgkin's lymphomas (NHLs), 19 secondary NHLs, 1 undetermined NHL, 1 lesion secondary to Hodgkin's disease, and 3 granulocytic sarcomas were reviewed with regard to histologic subtype, morphologic features, and immunophenotype. The median age of patients at presentation was 67 years for those with primary NHLs and 61 years for those with secondary NHLs. The majority of lymphomas were intermediate or high grade. Diffuse large cell type was by far the most common histologic subtype. No lymphomas resembling lymphomas of mucosa-associated lymphoid tissue were identified in this series, suggesting that such lymphomas are rare in breast compared with other sites such as the gastrointestinal tract and lung. Four primary NHLs, 2 secondary NHLs, and 1 granulocytic sarcoma were initially misdiagnosed as carcinomas; three patients underwent radical mastectomy, and at least three other patients nearly received surgical treatment. One primary anaplastic large cell lymphoma of B-cell origin was identified that closely resembled poorly differentiated ductal carcinoma. "Single file" or targetoid patterns with extensive sclerosis mimicking invasive lobular carcinoma was common in lymphomas and was seen in one of the granulocytic sarcomas. In addition, two breast lymphomas, one of B-cell phenotype and the other of T-cell phenotype, showed frequent signet ring cells, which potentially could be confused with lobular carcinoma. Despite a number of recent articles on lymphomas of the breast, it appears that these tumors continue to be confused with carcinomas. Histologic features suggestive of lymphomatous involvement include absence of in situ carcinoma, frequent individual karyorrhectic cells, lymphoepithelial lesions, and cellular discohesiveness.

Non-Hodgkin's lymphoma and skin malignancies-shared etiology?

The Stockholm-Gotland Cancer Register was used to evaluate the clinical observation that patients with non-Hodgkin's lymphoma (NHL) had an increased risk of malignant melanoma or squamous-cell carcinoma of the skin (SCCS) and vice versa. During 1958-1992, NHL was diagnosed in a total of 6,176 patients. Of these patients, 504 developed a second primary cancer of any type except NHL, compared to 301.9 expected, giving a standardized incidence ratio (SIR) of 1.7 [95% confidence interval (CI) 1.5-1.8]. The risk of SCCS and malignant melanoma in patients with NHL was 4.8 (95% CI 3.6-6.2; n = 54) and 1.7 (95% CI 0.8-3.1; n = 10), respectively. The hazard risk for a second malignancy was relatively constant over time, whereas the skin malignancies revealed the highest risks 3-10 years after initial diagnosis. Similarly, the risk of a secondary NHL was studied in patients with malignant melanoma and SCCS during the same period and found to be 1.3 (95% CI 0.8-2.1; n = 17) and 1.8 (95% CI 1.2-2.5; n = 34), respectively. The highest risk for NHL following malignant melanoma was seen 3-10 years after first diagnosis, while the highest risk following SCCS was observed 0-2 years after initial diagnosis. One of several possible explanations or the development of NHL and a skin malignancy in the same patient is an immunological defect caused by sun exposure.

Incidence of non-Hodgkin's lymphoma in patients treated for Hodgkin's disease.

The purpose of this study was to evaluate the incidence of non-Hodgkin's lymphoma (NHL) as a second tumor in patients treated for Hodgkin's disease (HD), as well as to establish the role of different variables in its appearance. Between January 1973 and June 1988, 101 patients with HD were treated according to the stage, with chemotherapy and/or radiotherapy. Complete remission was obtained in 87 patients. Five patients developed secondary NHL between the 77th and 124th month of complete remission. The median follow up was 73 months (range 3-227 months). The incidence of second NHL in our series was, 0%, 4.6% (CI 0-11%) and 17% (CI 4-32%) at 5, 10 and 15 years respectively. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, splenectomy, histology, stage and treatment modality) showed that the only statistically significant variable was the treatment received (p < 0.01). Cumulative incidence of NHL at 15 years, ranged from 0% for patients treated with radiotherapy or chemotherapy alone to 39.6% for those who received combined therapy (p = 0.002). We can conclude that the use of chemotherapy plus radiotherapy for treatment of HD increases the risk for the development of second NHL.

Mammographic and ultrasonographic appearances of lymphoma of the breast

A series of 11 malignant lymphomas of the breast (6 primary non-Hodgkin lymphomas, 4 secondary non-Hodgkin lymphomas, 1 Hodgkin's disease) is reported. Mammography, performed in 10 cases, revealed an ill-defined density (total or partial) (6 cases), a well-defined mass with multicyclic contours (2 cases), a mass with spiculations (1 case) and a false negative (1 case). The sonographic patterns analysed for 7 patients were non-specific, showing a higly hypoechoic, heterogenous mass with marginal irregularity in all cases. There was no correlation between the radiological appearances and the sonographic patterns; the latter were similar for both primary and secondary lesions. In contrast to mammography, ultrasonography has never been used in large literature series for diagnosis of these exceptional sites of lymphoma. Ultrasound also appears useful for patient follow-up to evaluate the response to treatment.

Lymphoma of the lung: CT findings in 31 patients.

Lymphomatous involvement of the lungs is often a difficult clinical and radiologic diagnosis to make, yet is often critical in determining treatment. To better define the CT appearance of pulmonary lymphoma, we undertook a retrospective review of 31 patients with recurrent or secondary non-Hodgkin lymphoma or Hodgkin disease and lung parenchymal involvement on CT scans. Diagnoses were confirmed either by lung biopsy or by disease regression or progression with appropriate therapy. The CT scans were evaluated for the following findings: (1) nodules less than 1 cm, (2) a mass or masslike consolidation greater than 1 cm with or without cavitations or bronchograms, (3) alveolar or interstitial infiltrates, (4) masses of pleural origin, (5) peribronchial or perivascular thickening with or without atelectasis, (6) pleural effusions, and (7) hilar or mediastinal lymphadenopathy. The most common CT finding was a mass or masslike consolidation larger than 1 cm, seen in 21 (68%) of the 31 patients. The second most common finding was nodules less than 1 cm (19 patients). Sixty-eight percent of patients had three or more of the CT abnormalities. Lymphoma involving the lung parenchyma causes a variety of CT findings, the most common being a mass or masslike consolidation. Two-thirds of patients have more than one type of CT finding simultaneously.