A woman with visual loss, amenorrhoea and polyuria: the first reported case of nodular lymphocyte-predominant Hodgkin lymphoma presenting with hypopituitarism.

SUMMARY: A 34-year-old woman presented 18 months post-partum with blurred vision, polyuria, amenorrhoea, headache and general malaise. Comprehensive clinical examination showed left superior temporal visual loss only. Initial investigations revealed panhypopituitarism and MRI demonstrated a sellar mass involving the infundibulum and hypothalamus. Lymphocytic hypophysitis was suspected and high dose glucocorticoids were commenced along with desmopressin and thyroxine. However, her vision rapidly deteriorated. At surgical biopsy, an irresectable grey amorphous mass involving the optic chiasm was identified. Histopathology was initially reported as granulomatous hypophysitis. Despite the ongoing treatment with glucocorticoids, her vision worsened to light detection only. Histopathological review revised the diagnosis to partially treated lymphoma. A PET scan demonstrated avid uptake in the pituitary gland in addition to splenic involvement, lymphadenopathy above and below the diaphragm, and a bone lesion. Excisional node biopsy of an impalpable infraclavicular lymph node confirmed nodular lymphocyte-predominant Hodgkin lymphoma. Hyper-CVAD chemotherapy was commenced, along with rituximab; fluid-balance management during chemotherapy (with its requisite large fluid volumes) was extremely complex given her diabetes insipidus. The patient is now in clinical remission. Panhypopituitarism persists; however, her vision has recovered sufficiently for reading large print and driving. To the best of our knowledge, this is the first reported case of Hodgkin lymphoma presenting initially as hypopituitarism. LEARNING POINTS: Lymphoma involving the pituitary is exceedingly rare and, to the best of our knowledge, this is the first reported case of nodular lymphocyte-predominant Hodgkin lymphoma presenting as hypopituitarism. There are myriad causes of a sellar mass and this case highlights the importance of reconsidering the diagnosis when patients fail to respond as expected to appropriate therapeutic intervention. This case highlights the difficulties associated with managing panhypopituitary patients receiving chemotherapy, particularly when this involves large volumes of i.v. hydration fluid.

Post-transplant hepatosplenic T-cell lymphoma successfully treated with HyperCVAD regimen.

Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma. In post-transplant immunosuppressed patients, HSTL is usually rapidly fatal. We report successful treatment of post-transplant HSTL in a 50-year-old renal allograft recipient by reducing immunosuppression and using intensive chemotherapy consisting of alternating cycles of HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and MTX/HiDAC (methotrexate, Ara-C). Remission is ongoing at 8+ years. Literature review identified another 20 cases of HSTL in solid organ transplant recipients: median survival was 4 months; no other patients survived beyond 12 months. Bone marrow involvement was universal, but changes were often subtle: 6 of 12 cases had nondiagnostic examinations earlier on. High index of suspicion may lead to more timely diagnosis of this uncommon form of post-transplant lymphoproliferative disorder, and treatment with intensive chemotherapy such as HyperCVAD may be curative.

Diagnostic pathology of lymphoproliferative disorders.

The last 20 years have seen a dramatic change in the way we classify, and therefore diagnose, lymphoma. Two decades ago, the International Working Formulation enabled diagnosis and management on the basis of H&E sections alone, with no mandatory requirement for immunophenotyping, molecular studies or any other ancillary investigations. The concept of categorisation by 'clinicopathological entities' defined by clinical features, morphology, immunophenotype and more recently, genotype, began with the Kiel, and Lukes and Collins classifications in the late 1970s, becoming fully expressed in the REAL and subsequently WHO classifications. The current, multidisciplinary approach to categorisation adds significantly to the task facing the anatomical pathologist, since it requires distribution of biopsy material to all the appropriate specialised laboratories, the gathering of a range of cross-disciplinary information, the correlation of all diagnostic findings, deduction of a definitive diagnosis and, finally, integration of all the above into a single multiparameter report. In this review, we summarise the contemporary approach to the biopsy, diagnosis and reporting of lymphoproliferative disorders.

The role of molecular studies in lymphoma diagnosis: a review.

Lymphoma classification is based on a multiparametric approach to diagnosis, in which clinical features, morphology, immunophenotype, karyotype and molecular characteristics are important to varying degrees. While in most cases, a diagnosis can be confidently established on the basis of morphology and immunophenotype alone, a small proportion of diagnostically difficult cases will rely on molecular studies to enable a definitive diagnosis. This review discusses the various molecular techniques available including Southern blotting (SB), polymerase chain reaction (PCR), fluorescence in situ hybridisation (FISH)--including multicolour-FISH/spectral karyotyping and comparative genomic hybridisation--and also gene expression profiling using cDNA microarray technology. Emphasis is given to the analysis of antigen receptor gene rearrangements and chromosomal translocations as they relate to lymphoma diagnosis and also in the setting of minimal residual disease (MRD) detection and monitoring. Laboratories performing these tests need to have expertise in these areas of testing, and there is a need for greater standardisation of molecular tests. It is important to know the sensitivity and specificity of each test as well as its limitations and the pitfalls in the interpretation of results. Above all, results of molecular testing should never be considered in isolation, and must always be interpreted in the context of clinical and other laboratory data.

A single-centre experience of post-renal transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) complicates 1 to 10% of all transplantations. Previous clinicopathological studies of PTLD have been limited by small numbers, short follow-up times, outdated data, heterogeneity of pooled solid-organ transplant results, and selective inclusion of early-onset disease. We therefore undertake here a retrospective analysis and identify all cases of PTLD that complicated renal transplantation at the Princess Alexandra Hospital between 30 June 1969 and 31 May 2001. Tumour samples were subsequently retrieved for pathological review and for Epstein-Barr virus-encoded RNA in situ hybridisation (EBER-ISH). Of 2,030 renal transplantation patients, 29 (1.4%) developed PTLD after a median period of 0.5 years (range 0.1 to 23.3 years). PTLD patients were more likely to have received cyclosporine (76% versus 62%, P<0.05), tacrolimus (10% versus 2%, P<0.05) and OKT3 (28% versus 10%, P<0.01). As the burden of immunosuppression increased from dual, to triple, to OKT3 therapy, the risks of early onset, extensive-stage, polymorphic, Epstein-Barr virus (EBV)-associated and fatal PTLD progressively increased. The majority of patients presented with an extra-nodal mass (45%), were afebrile (76%), and had stage-IV disease (60%). EBER-ISH was positive in 58%. Actuarial 5-year disease-free survival was 53.7%. The independent predictors of mortality on multivariate Cox regression were polymorphic histology (HR 7.4, 95% CI 1.5-37) and an international prognostic index (IPI) >1 (HR 2.7, 95% CI 1.1-6.8). Compared with other treatments, chemotherapy was associated with higher survival rates (100% versus 18% at 3 years, P=0.0001). In conclusion, PTLD is more likely, occurs earlier, and is more often fatal, in the setting of intensive immunosuppression. Nevertheless, excellent long-term outcomes are achievable with early recognition and institution of appropriate treatment.

Relapsed plasma cell leukaemia presenting with aggressive extramedullary plasmacytomas in the meninges and testis--a missed opportunity for induction CNS prophylaxis.

After initial treatment, a 54-year-old male with plasma cell leukaemia developed extramedullary relapse in the testis and meninges without evidence of bone marrow involvement. We postulate that the central nervous system (CNS) and testis may have served as sanctuary sites for the disease during initial treatment. A role for CNS prophylaxis in plasma cell leukaemia is suggested.

Identification of tumours with the CD43 only phenotype during the investigation of suspected lymphoma: a heterogeneous group not necessarily of T cell origin.

AIMS: CD43 is usually employed as a T cell marker in the immunophenotypic work-up of suspected cases of non-Hodgkin's lymphoma (NHL). In this setting, tumours expressing CD43 in the absence of other T or B cell markers (CD43 only phenotype) are rare. We present four cases with this aberrant phenotype seen at our institution. METHODS: The CD43 only phenotype was defined as expression of CD43 in the absence of expression of B cell markers CD20 and CD79a, and T cell markers CD3 and CD5, on initial immunohistochemistry performed on biopsies of suspected NHL. Combinations of further immunohistochemistry, flow cytometry, cytogenetic analysis and molecular studies were used to enable further diagnosis and lineage assignment. RESULTS: The four cases were subsequently diagnosed as: one case of extramedullary acute myeloid leukaemia, one case of null cell anaplastic large-cell lymphoma, and two cases of extranodal diffuse large B cell lymphoma. None were demonstrated to be of T cell origin. CONCLUSIONS: Our series further confirms the lack of specificity of CD43 expression for T cell lineage. Documentation of the CD43 only phenotype in suspected cases of NHL therefore requires further investigation to both correctly diagnose and clarify lineage of these tumours.