Pitfalls in lymphoma pathology: avoiding errors in diagnosis of lymphoid tissues

The complexity involved in the histological interpretation of lymph nodes and other lymphoid tissue specimens suspected of harbouring lymphoma is underappreciated. As with other histology specimens, the quality of sections and background information are crucial but so, increasingly, is the appropriate use of immunocytochemistry and a variety of molecular analyses. Within the UK National Health Service, progressive regional centralisation is ongoing, to ensure access to specialist expertise and a full range of testing beyond traditional stains. This is to be welcomed but there remains a need to maintain skills in smaller district hospitals, to ensure lymphoma recognition in unexpected circumstances, to permit clinically useful interim diagnoses when needed urgently and to sustain training in haematopathology among junior pathologists. In this review a range of potential pitfalls in lymphoid tissue pathology is outlined, arising at all stages from specimen preparation to reporting. Knowledge of such pitfalls, some of which are common while others are rare but of vital clinical importance, should help increase confidence in lymphoma diagnosis among histopathologists.

[1]  F. Mayall,et al.  A review of 50 consecutive cytology cell block preparations in a large general hospital. , 1997, Journal of clinical pathology.

[2]  S. Banerjee,et al.  Audit of tumour histopathology reviewed by a regional oncology centre. , 1995, Journal of clinical pathology.

[3]  Juan F. García,et al.  Intrafollicular neoplasia/in situ follicular lymphoma: review of a series of 13 cases , 2010, Histopathology.

[4]  K. Amara,et al.  Prognostic significance of aberrant promoter hypermethylation of CpG islands in patients with diffuse large B-cell lymphomas. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  J. Lester,et al.  The clinical impact of expert pathological review on lymphoma management: a regional experience , 2003, British journal of haematology.

[6]  L. Medeiros,et al.  B-Cell Lymphoma, Unclassifiable, with Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma , 2013 .

[7]  P. Went,et al.  Prognostic immunophenotypic biomarker studies in diffuse large B cell lymphoma with special emphasis on rational determination of cut-off scores , 2010, Leukemia & lymphoma.

[8]  X. Zhao Pitfalls in diagnostic hematopathology: part I. , 2009, International journal of clinical and experimental pathology.

[9]  Matija Snuderl,et al.  B-cell Lymphomas With Concurrent IGH-BCL2 and MYC Rearrangements Are Aggressive Neoplasms With Clinical and Pathologic Features Distinct From Burkitt Lymphoma and Diffuse Large B-cell Lymphoma , 2010, The American journal of surgical pathology.

[10]  A. Bagg,et al.  B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma , 2012 .

[11]  J. Chi,et al.  Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma , 2008, Journal of cellular and molecular medicine.

[12]  S. Swerdlow,et al.  The proliferation center microenvironment and prognostic markers in chronic lymphocytic leukemia/small lymphocytic lymphoma. , 2006, Human pathology.

[13]  B. Bain,et al.  Best Practice in Lymphoma Diagnosis and Reporting , 2012 .

[14]  G. Aralica,et al.  The accuracy of fine needle aspiration cytology and flow cytometry in evaluation of nodal and extranodal sites in patients with suspicion of lymphoma. , 2010, Collegium antropologicum.

[15]  D. Poller,et al.  Referrals for second opinion in surgical pathology: implications for management of cancer patients in the UK. , 2001, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[16]  D. Howlett,et al.  Diagnostic adequacy and accuracy of fine needle aspiration cytology in neck lump assessment: results from a regional cancer network over a one year period. , 2007, The Journal of laryngology and otology.

[17]  A. LaCasce,et al.  Comparison of referring and final pathology for patients with non-Hodgkin's lymphoma in the National Comprehensive Cancer Network. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  W. Chan,et al.  Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma , 2005, Modern Pathology.

[19]  S. Serrano,et al.  FISH is better than BIOMED-2 PCR to detect IgH/BCL2 translocation in follicular lymphoma at diagnosis using paraffin-embedded tissue sections. , 2008, Leukemia research.

[20]  A. Carbone,et al.  B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology. , 2010, Human pathology.

[21]  M Hummel,et al.  Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936 , 2003, Leukemia.

[22]  L. Staudt,et al.  Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. , 2004, Blood.

[23]  E. Montserrat,et al.  Chronic lymphocytic leukaemia/small lymphocytic leukaemia. , 2001 .

[24]  P. Isaacson Haematopathology practice: the commonest problems encountered in a consultation practice , 2007, Histopathology.

[25]  W. Chan,et al.  Prognostic value of cellular proliferation and histologic grade in follicular lymphoma. , 1995, Blood.

[26]  L. Bereczki,et al.  Optimization of PCR amplification for B-and T-cell clonality analysis on formalin-fixed and paraffin-embedded samples , 2008, Pathology & Oncology Research.

[27]  X. Zhao Pitfalls in diagnostic hematopathology -- Part II. , 2009, International journal of clinical and experimental pathology.

[28]  Kai Fu,et al.  A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy , 2009, Clinical Cancer Research.

[29]  N. Aluwihare,et al.  The role of freehand needle core biopsy in the diagnosis of isolated axillary lymphadenopathy. , 2009, Breast.

[30]  D. Gonzalez,et al.  Improved clonality assessment in germinal centre/post-germinal centre non-Hodgkin’s lymphomas with high rates of somatic hypermutation , 2006, Journal of Clinical Pathology.

[31]  J. Raemaekers,et al.  The prognostic significance of the intra-follicular tumor cell proliferative rate in follicular lymphoma. , 2007, Haematologica.

[32]  Y. Kwong,et al.  Common misdiagnoses in lymphomas and avoidance strategies. , 2010, The Lancet. Oncology.

[33]  S. Richards,et al.  The development of integrated haematopathology laboratories: a new approach to the diagnosis of leukaemia and lymphoma. , 2003, Clinical and laboratory haematology.

[34]  K. Imrie,et al.  In situ localization of follicular lymphoma: evidence for subclinical systemic disease with detection of an identical BCL-2/IGH fusion gene in blood and lymph node , 2009, Leukemia.

[35]  R. Siebert,et al.  FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue. , 2006, The Journal of molecular diagnostics : JMD.

[36]  T. Golub,et al.  Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. , 2004, Blood.

[37]  B. Coiffier,et al.  Nodular, lymphocyte‐predominant Hodgkin lymphoma , 2010, Cancer.