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Lymphoma is the most common primary tumor of the orbit, accounting for 55% of all orbital malignancies. When divided into histopathological subtypes, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises the largest proportion. Clinical manifestations are unspecific, but in patients with slow-growing painless orbital mass, or red conjunctival lesion suggestive of ‘salmon patch’, ocular adnexa lymphoma (OAL) should be suspected. Although the pathogenetic mechanism of ocular adnexal MALT lymphoma (OAML) is not yet fully understood, the relationship between OAML and Chlamydia psittaci has been hypothesized recently, similar to that between gastric MALT lymphoma and Helicobacter pylori. This suggests a new treatment option for OAML; bacterial eradication therapy with systemic antibiotics. Several other treatment methods for OAML have been introduced, but no treatment guidelines have been established yet. In this article, we summarize the current knowledge on the clinical features, pathogenesis, diagnostic methods, therapeutic strategies, and prognosis of OAML.

Ocular adnexal lymphoma accounts for approximately 1%-2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Lacrimal gland lymphoma, especially bilateral lacrimal gland lymphoma, is rare, and imaging is often utilized to differentiate lacrimal lymphoma from other types of masses that involve the lacrimal gland and the fossa. We describe a 74-year-old male patient presenting with bilateral eye proptosis, lachrymose without pain, and no changes in eyesight. Brain-orbit magnetic resonance imaging revealed bilateral lacrimal fossa masses with regular contours, moderate enhancement, and restriction on diffusion imaging, consistent with a lymphoma diagnosis, which was confirmed by histopathological results. Positron emission tomography-computed tomography was used to determine lymphoma grading. MRI, especially diffusion imaging, can be useful for guiding clinicians in the diagnosis and differentiation of lacrimal gland lymphoma from other lesions.

BACKGROUND N-isopropyl- (123I) p-iodoamphetamine (123I-IMP) is specifically accumulated in primary central nervous system lymphoma (PCNSL) during single-photon emission tomography (SPECT) and contributes to its diagnostic imaging. However, whether 123I-IMP is accumulated in ocular adnexal lymphoma (OAL), one of the malignant intraorbital tumors, remains unclear. This study aimed to evaluate the diagnostic value of 123I-IMP SPECT in OAL. METHODS Between August 2005 and June 2020, 26 patients with intraorbital tumors underwent neurosurgery at the tertiary care center. Of these, 15 patients who underwent 123I-IMPSPECT before surgery were retrospectively examined. The region of interest was set in the cerebellum ipsilateral to the intraorbital tumor on 123I-IMP SPECT, and the tumor-to-cerebellum ratio (T/C ratio) was calculated using the following formula: T/C ratio = [accumulation of tumor (count/pixel)]/[accumulation of ipsilateral normal cerebellar hemisphere (count/pixel)]. RESULTS Six patients were included in the OAL group, who were pathologically diagnosed with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), diffuse large B-cell lymphoma (DLBCL), and plasmacytoma. The T/C ratio in the OAL group was statistically higher than that in the non-OAL group (p

PURPOSE Helicobacter pylori could theoretically induce ocular adnexal lymphoma (OAL) via 2 mechanisms: the first is that of infection within the ocular adnexa and the second is that of infection within the gastric mucosa, leading to the malignant transformation of lymphocytes that migrate to the ocular adnexa, forming a primary "ectopic" cancer. This study investigated if an association exists between gastric H. pylori or ocular adnexal H. pylori and OAL. METHODS Prospective case-control study including cases with OAL and controls with nonlymphomatous pathologies. Gastric H. pylori infection was assessed via serologic antibody testing. Ocular adnexal infection was assessed via polymerase chain reaction testing for H. pylori and Chlamydia psittaci within ocular adnexal samples. RESULTS Seventy-two patients were enrolled, of whom 18 had lymphoma and 54 nonlymphomatous pathologies. H. pylori antibodies were present in 5 cases (28%) and 18 controls (33%) (95% CI, 0.24%-2.50%, p = 0.78). All ocular adnexal specimens were negative for H. pylori and C. psittaci infection. The only relevant statistically significant difference between cases and controls was a history of gastric ulcer (95% CI, 1.23%-44.80%, p = 0.03). CONCLUSIONS In the study's population, infection of gastric mucosa with H. pylori does not appear to influence the development of OAL. Also, H. pylori or C. psittaci infection within the ocular adnexa does not appear to influence the development of OAL. In the study's practice, authors do not recommend antibiotic administration or routine gastroscopy for patients with OAL. The authors do recommend referral of OAL patients with gastric symptoms to a gastroenterologist.

Annemarie Klingenstein,1 Aylin Garip-Kuebler,1 Siegfried Priglinger,1 Christoph Hintschich,1 Ullrich G Mueller-Lisse2 1Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany; 2Department of Radiology, Ludwig-Maximilians-University, Munich, GermanyCorrespondence: Annemarie KlingensteinLudwig-Maximilians-University, Department of Ophthalmology, Klinikum der Universität München, Campus Innenstadt, Mathildenstraße 8, Munich, D-80336, GermanyTel +49 89 44005 3811Fax +49 89 44005 5160Email Annemarie.Klingenstein@med.uni-muenchen.deAim: To detect radiological features that, in addition to clinical findings, may aid in correct differentiation between IgG4-related ophthalmic disease (IgG4-ROD) and ocular adnexal lymphoma (OAL).Methods: In this retrospective, single-center, comparative analysis, we compared cross-sectional imaging findings of 13 consecutive patients with histologically proven IgG4-ROD and a control group of 29 consecutive OAL-patients diagnosed between 10/2014 and 09/2019. Statistical significance was accepted at a p< 0.05 significance level.Results: IgG4-ROD-patients had longer time-to-diagnosis, higher orbital recurrence rates, but smaller lesions compared to OAL-patients (p=0.002; p=0.006 and p=0.006; Mann–Whitney U-test). Frequent cross-sectional imaging findings in both IgG4-ROD-patients and OAL-patients included extraocular muscle enlargement (92% and 93%, respectively; most often in the lateral rectus muscles and the levator-complex), and lacrimal-gland enlargement (85% and 83%, respectively). Other imaging findings comprised infraorbital nerve-involvement (IgG4-ROD, 23%, OAL, 17%) and orbital fat inflammation (IgG4-ROD, 23%, OAL, 28%). Bony infiltration and remodeling, heterogenous contrast-media distribution, and infiltration of the lacrimal system were seen slightly more often in IgG4-ROD (23%, 38%, 15% and 15% versus 17%, 14%, 3% and 7%). However, cross-sectional imaging features did not differ significantly between patient subgroups. Clinical symptoms predominantly occurred unilaterally (IgG4-ROD, 9/13, 69%, OAL, 24/29, 83%), while imaging findings were most often bilateral (IgG4-ROD, 11/13, 85%, OAL, 23/29, 79%, p< 0.001, McNemar test).Conclusion: No morphological cross-sectional imaging sign could reliably distinguish between IgG4-ROD and OAL, leaving histopathology indispensable for definite diagnosis. Yet, importantly, for both IgG4-ROD and OAL, cross-sectional imaging frequently detected bilateral orbital disease when only one eye was clinically affected.Keywords: IgG4, idiopathic orbital inflammation, CT, ocular adnexal lymphoma

Detailed information regarding follow-up of ocular adnexal lymphoma and of the frequency of large cell transformation of low-grade ocular adnexal lymphoma is limited. We studied 174 patients with ocular adnexal lymphoma (OAL) to evaluate long-term clinical outcome and patterns of failure. All lymphomas presenting with involvement of the ocular adnexa diagnosed at the Massachusetts General Hospital (MGH) between 1974 and 2007, in which at least 6 months of follow-up was available, were included in this study. There were 106 extranodal marginal zone lymphomas (MALT lymphomas, MZL), 40 follicular lymphomas (FL), 16 diffuse large B cell lymphomas (DLBCL), 5 mantle cell lymphomas (MCL), 3 small lymphocytic lymphomas/chronic lymphocytic leukemias, 1 lymphoplasmacytic lymphoma, 2 B lymphoblastic lymphomas, and 1 extranodal NK/T cell lymphoma. Relapses occurred in 42 of 106 MZL patients (40%) and in 14 of 40 FL patients (35%). Two MZL and one FL progressed to DLBCL. Five and 10-year relapse-free survival (RFS) and five and 10-year overall survival (OS) respectively were: MZL 67%, 36%, 93%, 88%; FL: 54%, 32%, 90%, 82%; DLBCL: 79%, 79% 88%, 88% MCL: 20%, 0%, 100%, 25%. MZL and FL patients often developed relapses but had long survival; progression to DLBCL was uncommon. DLBCL had a favorable prognosis. MCL had a poor prognosis.

Aim Modern radiotherapy (RT) technique and therapy de-escalation have led to encouraging results in lymphoma management. In this study, we aimed to describe the oncological and toxicity outcome in patients with ocular adnexal lymphoma. Patients and methods A total of 45 patients with 52 orbital lesions who were treated at our Institution between 2003 and 2019 were considered. Clinical characteristics, treatment outcomes, and toxicity were assessed. Patients receiving 4-6 Gy were categorized as receiving ultra-low-dose RT, 24-30.6 Gy as standard-dose RT, and >30.6 Gy as high-dose RT. Results The predominant histological subtype was marginal zone lymphoma in 39 lesions (75%). Radiation dose ranged from 4-50.4 Gy. In the whole cohort, 11% of the lesions were treated with ultra-low-dose RT, 33% with standard-dose RT, and 56% with high-dose RT; 60% of lesions were treated using intensity-modulated RT (IMRT), while 44% of lesions were treated with partial orbital RT. The median duration of follow-up was 33 months. The overall response rate was 94% (complete response rate=83%). The 5-year local control rate, progression-free survival, and overall survival were 100%, 76%, and 92%, respectively. We did not detect any significant difference in progression-free or overall survival regarding different radiation doses and volumes. Ultra-low-dose RT was associated with a significantly lower rate of grade 2 late toxicities (0% vs. 6% and 31%, p=0.05) in comparison with standard-dose and high-dose RT, respectively. Patients who received IMRT had a significant fewer acute grade 2 (16% vs. 43%, p=0.05) and a trend towards lower late grade 2 toxicities (9% vs. 33%, p=0.06). Conclusion Radiation dose and volume de-escalation seem to be safe and effective, with excellent local control and survival in the management of ocular adnexal lymphoma. IMRT seems to be associated with less toxicity.

Purpose: To assess the characteristics and treatment outcomes of patients with primary ocular adnexal lymphoma (OAL) in Northern Thailand. Design: Retrospective cohort study. Methods: Data was collected from electronic medical records and operative notes from Chiang Mai University Hospital between January 2009 and December 2014. All available tissue biopsies of 54 patients were reviewed by agreement of two pathologists. The clinical characteristics and treatment outcomes were collected and analyzed. Results: A total number of 54 patients were identified of which 57.4% were female. The median age was 61.0 years (range, 4-86). The most common subtype of lymphoma was extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT) (n = 46, 85.2%). Seventy-five percent of the patients presented with a mass at the ocular adnexa, while 14.8% of the patients presented with proptosis. The sites of origin were as follows: lacrimal (46.3%), orbit (31.5%), conjunctiva (13%) and eyelid (7.4%). Two-thirds of the patients had Ann-Arbor Stage I, while 22% of patients had Stage IV. The majority of the patients (68.1%) had a low-risk international prognosis index (IPI). Treatment modalities involved field radiation (IFRT, 50%), chemotherapy (31.6%), combined chemoradiotherapy (7.9%) and surgical resection (10.5%). The overall response rate was 100% with a complete response rate of 77.8%. In patients with low-grade lymphoma, including MALT lymphoma, the 3-year progression-free survival (PFS) and overall survival were 69.9% and 92.5%, respectively. Conclusion: ENMZL of MALT was the major subtype of primary OAL. Radiotherapy was an effective treatment for the lower stages of disease providing a high response rate and encouraging survival outcomes.

Ocular adnexal lymphoma (OAL) refers to extremely rare, heterogeneous, malignant lymphoproliferative disorder that accounts for 55% of all orbital tumors and 5% of extranodal lymphomas. OAL can com...

The authors report a single case of diffuse large B-cell lymphoma arising in the lacrimal sac. Diffuse large B-cell lymphoma is a third most common primary ocular adnexal lymphoma, which is the most common primary ocular malignant disease in adults. A patient came to our clinic with epiphora and a growing mass in the lacrimal sac. Enhanced computed tomography imaging suggested the presence of a malignant tumor and surgical excision and biopsy were performed. A final diagnosis of diffuse large B-cell lymphoma was reached by immunohistological and immunochemical staining. Two months after surgery, diffuse large B-cell lymphoma relapse occurred in the lacrimal sac and the patient underwent 6 cycles of chemotherapy. Diffuse large B-cell lymphoma is a curable disease when diagnosed early, and aggressive biopsy during surgery of the lacrimal sac is necessary to diagnose diffuse large B-cell lymphoma in the early stage. It is important to distinguish diffuse large B-cell lymphoma from other lacrimal system diseases.

BackgroundNationwide studies of ocular adnexal lymphoma (OAL) are very rare in the literature, and knowledge on incidence, subtype distribution and long-term survival data is limited. This is the largest national study of OAL to date. This study sought to find information on incidence, changes in incidence, clinical findings, distribution of subtypes, survival and prognostic factors.MethodsPatients diagnosed with OAL from January 1, 1980 to December 31, 2017 were identified in Danish registers, and clinical as well as survival data were collected. The data were analysed with Kaplan-Meier plots and log-rank test.Results387 patients were included in the study. The major lymphoma subtypes were extranodal marginal-zone B cell lymphoma (EMZL) (55%), diffuse large B cell lymphoma (DLBCL) (13%), mantle cell lymphoma (MCL) (11%) and follicular lymphoma (FL) (10%). OAL is a disease of the elderly (median age 69 years). The incidence of lymphoma of the ocular adnexal region has increased significantly throughout the time period of the study (Pearson correlation coefficient, r=0.65; PConclusionOAL is increasing in incidence in the Danish population for unknown reasons. However, the prognosis for most OAL is favourable, as highlighted in this national long-term study.

Introduction: Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy. Patient concerns: A 60-year-old man presented with a left salmon-colored conjunctival mass. Diagnosis: A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio. Interventions: Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy. Outcomes: Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma. Lessons: Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.

Objectives To assess the prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis in ocular adnexa lymphoma (OAL) determined by molecular testing in different countries and the potential association of Chlamydia infection with mucosa-associated lymphoid tissue (MALT) histotype by performing a systematic review and meta-analysis. Methods Electronic databases were searched for studies assessing the presence of Chlamydia in OAL. Pooled prevalence of the three Chlamydia species was calculated in each country. An odds ratio was calculated for the association between Chlamydia and MALT histotype, with a significant P < .05. Results Thirty-seven studies with 1,188 OALs were included. Pooled prevalence of C psittaci, C pneumoniae, and C trachomatis by country was done. Chlamydia infection was significantly associated with MALT histotype (odds ratio, 2.183; P = .027). Conclusions The involvement of C psittaci in OAL is highly variable, with the highest prevalence in Italy and Korea. Chlamydia is associated with MALT histotype.

Multiple myeloma (MM) is the second most prevalent hematologic malignancy after non-Hodgkin lymphoma and is currently considered incurable. Clinical ophthalmic manifestations of MM are rare but at the same time diverse. Ocular surface manifestations of multiple myeloma are uncommon. Conjunctival 'salmon patch' is a typical ocular surface ophthalmological sign with a distinct set of differential diagnoses, including most often ocular adnexal lymphoma. This case report presents a 33-year-old female with a relapse of MM manifesting as a conjunctival 'salmon patch'. The patient initially responded well to medical management including high dose melphalan supported by a third autologous stem cell transplantation (ASCT) and did not require further surgical excision of the ocular lesion. It is suggested that MM should be included in the differential diagnosis of 'salmon patch' conjunctival lesions.

Compared to ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) patients with symptoms related invasion beyond the ocular adnexa, the different approaches to staging assessment may be required in OAML patients with symptoms limited to the ocular adnexa. Seventy-six patients to be diagnosed with OAML and performed bone marrow biopsy and imaging study at Yeungnam University Hospital in 1995–2014 were enrolled. Patients with symptoms limited to the ocular adnexa were included. Computed tomography, magnetic resonance imaging, positron emission tomography (PET), and bone marrow biopsies were performed for diagnosis, NM staging and follow up evaluation. Most patients were treated with external beam irradiation (median dose, 30 Gray (Gy)). The relapse-free survival (RFS) was analyzed according to the tumor laterality and TNM stage. The median follow-up period was 72 months. The 5-year RFS and overall survival rates were 82.1% and 95.6% respectively. Of all 76 patients, lymph node and bone marrow involvement was identified in 1 patient, respectively. Among the 3 patients with T4 stage as tumor invasion beyond ocular adnexa, bone marrow involvement was confirmed in a patient with left cheek invasion. Only 11 of the 43 patients who underwent PET showed positive uptakes in orbital lesion. The patients with advanced stage were alive without recurrences. Bone marrow examination is useful in OAML patients with T4 for extended stage assessment. The AJCC TNM staging system was not significantly predictive factor for relapse, but may contribute to clarifying the patient group that needs bone marrow study.

High-grade B-cell lymphoma (HGBL) with c-MYC and BCL2 and/or BCL6 rearrangements, also known as a double-hit and triple-hit lymphoma, is an aggressive non-Hodgkin lymphoma affecting older adults. After formal recognition of this entity in the 2017 revision of the World Health Organization Classification of lymphoid neoplasms, only two well-documented cases of triple-hit lymphoma of the orbit appear in the literature. Herein, we describe a 70-year-old man with progressive diplopia, ophthalmoplegia, and rapidly enlarging temporal mass. Biopsy revealed a tumor morphologically consistent with HGBL, coexpressing CD20, CD10, BCL6, BCL2, and c-MYC on immunohistochemical analysis. Fluorescence in-situ hybridization showed rearrangements in c-MYC and BCL-2 genes, confirming double-hit HGBL. Systemic workup revealed Ann Arbor stage IV disease. This report reviews the existing literature on ocular adnexal double-hit and triple-hit lymphoma and provides an update on the diagnostic ancillary studies, prognostic implications, and latest management for this aggressive hematolymphoid malignancy.

Primary diffuse large B cell lymphoma of the conjunctiva is a rare disease. In this article, we report the case of a 40-year-old man who had previously been treated with chemotherapy and radiotherapy for undifferentiated carcinoma of nasopharyngeal type (UCNT) and who subsequently developed conjunctival lymphoma. We underline through this observation the importance of thinking about a secondary cancer post-radio-chemotherapy even when the clinical presentation is atypical.

Background: Increased risk of developing cancer in patients with Immunoglobulin G4-related disease (IgG4-RD) have been reported. Association of malignancies and IgG4-related ophthalmic disease (IgG4-ROD), however, remains unclear. Methods: A retrospective review of medical records, orbital images and histopathology reports from 2005 to 2019 in a territory-wide, biopsy-proven cohort, fulfilling the “probable” or “definite” comprehensive diagnostic criteria of IgG4-RD. Findings: All 122 patients had biopsies taken from single or multiple ocular adnexal lesions including lacrimal glands (n=108), discrete orbital masses (n=30), infiltrated orbital fat (n=10), conjunctiva(n=2) or extraocular muscles (n=3). Totally 16 (13%) patients developed cancer over 73±48 months’ follow-up. 9 developed ocular adnexal lymphoma (OAL) and 7 had extra-orbital malignancies. The incidence of OAL was significantly higher (standardized incidence ratios (SIRs) =10.0, 95%CI=4.5-17.6) while that of extra-orbital malignancies was similar (SIRs=0.54, 95%CI=0.2-1.0) to the general population. The risk of OAL was highest within the first year of IgG4-ROD diagnosis (SIRs=46.7, 95%CI=18.5-87.6) as 7 of the 9 OAL were diagnosed concomitantly with IgG4-ROD. Patients who developed OAL or extra-orbital malignancies were older at the time of diagnosis of IgG4-ROD compared to the rest of the cohort (64.9±7.1 years and 68.3±8.5 years versus 55.2±15.0 years, both p

Amyloidosis is a protein metabolism disorder characterised by extracellular deposition of insoluble amorphous hyaline material. Orbital and ocular amyloid lesions account for only 4% of localised disease affecting the head and neck. Ocular adnexal lymphoma accounts for 1-2% of lymphoma, with lacrimal gland lymphomas being relatively uncommon. The most common form affecting the orbit is extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT lymphoma). We report an extremely rare case of co-existent EMZL and amyloidosis of the lacrimal gland. Initial biopsy of the right lacrimal gland confirmed an EMZL with amyloid deposit, and a course of radiotherapy treatment was given. Recurrent lacrimal gland swelling developed within a year. Subsequent biopsy identified amyloidosis with scanty lymphoid tissue. To our knowledge, this is the first reported case of localised lacrimal gland amyloidosis of uncertain type with previous EMZL; the association described in this case report is not yet fully understood.

Purpose: Ocular adnexal lymphomas (OAL) constitute 55% of all orbital tumors. Waldenström Macroglobulinemia (WM) presenting as an orbital mass with diffuse extraocular muscle (EOM) involvement is rare. We report an elderly patient who presented to the ophthalmologist for an orbital mass which on evaluation, turned out to an ocular adnexal WM. Observations: A 75 years old man presented with a palpable mass in the left anterior superior orbit and bilateral restricted ocular motility in all gazes. Computed tomography scan revealed a hyperdense mass with diffuse thickening of extraocular muscles and enlarged lacrimal gland on the left side. Incisional biopsy of the mass revealed a lymphoproliferative neoplasm with plasmacytic morphology. Immunohistochemistry (IHC) of the orbital mass as well as the bone marrow was sought, lymphoplasmacytic lymphoma (CD20+, CD38+, MUM1+, BCL 2+, CD3−, CD5−, CD10−, CD23−, cyclin D1). Bone marrow flow cytometry showed CD5−, CD10− kappa restricted B cell neoplasm. Serum analysis significantly elevated IgM levels. This indicated a diagnosis of ocular adnexal Waldenström Macroglobulinemia. Conclusion and importance: This case highlights the importance of clinical evaluation, histopathology, and immunohistochemistry for phenotyping of ocular adnexal lymphomas.

PURPOSE To investigate the clinical features and outcomes of diffuse large B-cell lymphoma (DLBCL) involving the eye and ocular adnexa in an East Asian population and emphasize the importance of prompt biopsy and treatment in unusually progressive ocular adnexal DLBCL for better visual outcomes. METHODS Retrospective case series of 38 patients diagnosed with DLBCL involving the eye and ocular adnexa between 1995 and 2018 at a single tertiary institution. RESULTS There were 38 patients (22 men, 16 women), 22 (57.9%) of which had ocular adnexal lymphoma (OAL) and 16 (42.1%), vitreoretinal lymphoma (VRL). The OAL group showed higher rates of unilateral involvement (p = 0.01) and localized disease presentation (p = 0.01). Thirteen (59.1%) of 22 OAL patients were primary diseases and 9 (40.9%) were secondary. Between primary and secondary OAL groups, there was no statistical difference in clinical characteristics such as age, gender and laterality (p = 0.47, p = 0.19 and p = 0.66, respectively). All secondary OAL cases were either disseminated or relapsed by definition and only two cases (15%) of primary OAL showed disseminated presentation (p