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Histopathological methods based on 2 μm thin sections are routinely used in pathological anatomical diagnosis. Many medical disciplines already rely on a 3D representation, regarding visualization and imaging techniques. Pathology in particular uses different tissue visualizations to make the final diagnosis. Thereby, a standard 2D histological section only represents a flat snapshot of a three-dimensional complex cell system. Despite that, 3D cell analysis is not yet standardly used in clinical routine. This work used 3D analysis systems to investigate the morphological alterations of the fibroblastic reticular cell network inside human lymph nodes during neoplastic transformation and evaluates the added value of 3D visualizations in tissue interpretation. We investigated the surface and volume quotient, cell cross-linking and percentage cell volume of the fibroblastic reticular cell (FRC) network inside Lymphadenopathy (follicular hyperplasia) (LAD), Follicular Lymphoma Grade 1 (FL1), Nodular Sclerosis classical Hodgkin Lymphoma (NScHL) and Angioimmunoblastic T-Cell Lymphoma (AITL). We found that the average quotient of LAD and FL1 differed from those of NScHL and AITL, indicating that the surface and volume quotient changes in the course of neoplastic transformation. This is probably due to an increased network convolution, while the total cell volume remains the same at about 2%. In conclusion, this paper describes the tumor-related morphological changes of the FRC network, which would have been difficult to achieve without the use of 3D analysis systems.

Smooth muscle myosin heavy chain (SMMHC) is a major structural component of the contractile apparatus in smooth muscle cells. Even though it is considered a relatively specific marker for terminal smooth muscle cell differentiation, expression in other cell types such as follicular dendritic cells (FDCs) has rarely been reported. To determine whether SMMHC represents an effective FDC marker in lymphoid tissues, we compared the immunohistochemical results for SMMHC with those of the traditional FDC markers podoplanin (D2-40) and CD21. Paraffin sections of 44 lymphoid tissues were analyzed, including 31 cases of follicular hyperplasia, 6 cases of follicular lymphoma, 2 cases of peripheral T-cell lymphoma, 3 cases of diffuse large B-cell lymphoma arising in follicular lymphoma, 1 case of nodular sclerosis classical Hodgkin lymphoma, and 1 case of small lymphocytic lymphoma. There was no statistically significant difference between the number of SMMHC-positive and D2-40-positive or CD21 lymph nodes (P>0.05). The extent and intensity of SMMHC-positive FDCs were similar to those of D2-40-positive FDCs (P=0.127 and 0.733, respectively), but significantly lower compared with those of CD21 cells (P=0.009 and 0.00002, respectively). However, in contrast to CD21 which was also positive in some germinal center B cells, SMMHC expression was restricted to FDCs. Our results indicate that SMMHC is an excellent marker for FDCs and can be particularly helpful in demonstrating the underlying architecture in lymphoid processes.

Human immunodeficiency virus (HIV) is associated with an increased risk of developing Hodgkin lymphoma (HL). South Africa (SA) has the highest HIV prevalence rate in the world. There is currently no outcome-based data for HIV-associated HL from SA. A bone marrow database was compiled of all bone marrow biopsies (BMB) reported at National Health Laboratory Service (NHLS) Groote Schuur Hospital (GSH) between January 2005 and December 2012. Patients who had a BMB performed for staging of HL or where HL was diagnosed on the BMB were included for further analysis. Clinical and laboratory data was extracted from medical and laboratory records. Primary outcome measures included histological subtype, bone marrow infiltration (BMI) by HL, CD4 count, HIV-viral load (HIV-VL), tuberculosis (TB) data, treatment with chemotherapy and 5-year overall survival (OS). The database included 6569 BMB and 219 patients of these had HL and were included for analysis. The median age at presentation (32 years) was similar in the HIV+ and HIV− populations. While males predominated in the HIV− group, females predominated in the HIV+ group (male:female ratio of 1.5:1 vs 0.7:1, respectively). The majority of patients (71%) were HIV negative (HIV−) and 29% were HIV positive (HIV+). The diagnosis of HL was made on BMB in 17% of cases. BMI was seen in 37% (82/219) overall, and was found in more HIV+ patients (61%; 39/64) than HIV− patients (28%; 43/155; p = 0.03). The histological subtype varied according to HIV status with nodular sclerosis classical Hodgkin lymphoma (NSCHL) being most frequent in the HIV− group and classical Hodgkin lymphoma (CHL)-unclassifiable the most frequent in the HIV+ group. HIV+ patients had a median CD4 count of 149 × 106/L and 39% were anti-retroviral therapy (cART) naive at HL diagnosis. HIV+ patients had received anti-TB therapy more frequently than HIV− patients (72% vs 17%; p = 0.007). More HIV+ patients did not receive chemotherapy than HIV− patients (31% vs 3%; p = 0.001). The 5-year OS was 56%. HIV+ patients with BMI had a 5-year OS of 18%. BMI, HIV status, low CD4 count, histological subtype and TB therapy had a statistical significant impact on 5-year OS (p

BACKGROUND Grade 2 nodular sclerosis classical Hodgkin lymphoma (NSCHL) is less common than grade 1 lymphoma and has a worse overall prognosis. To the best of the authors' knowledge, no study of a large series of cases has been performed until now. The objective of this study was to assess the diagnostic efficacy of cytology for grade 2 NSCHL versus grade 1 NSCHL and study the morphological features of grade 2 NSCHL in fine-needle aspiration cytology (FNAC). METHODS Fifteen of 51 histopathology-proven cases of NSCHL (18 FNAC procedures) were grade 2, and 36 were grade 1. The efficacy of FNAC for detecting grade 1 and 2 NSCHL was assessed, and the frequency of misdiagnosis was compared. The clinical details and cytomorphological features of grade 2 NSCHL were studied in detail. RESULTS Among the grade 1 NSCHL patients, 58.4% were diagnosed with Hodgkin lymphoma (HL) or had findings suggestive of HL, whereas 20% of the grade 2 patients were diagnosed HL or suggestive of HL. Two cases of grade 2 NSCHL were misdiagnosed as anaplastic large cell lymphoma, and 4 were misdiagnosed as malignant neoplasms. Grade 2 NSCHL cases showed clusters and sheets of mononuclear, multinucleated, and bizarre cells, with some cases showing a suppurative background. However, extensive searching showed occasional Reed-Sternberg (RS) cells in most of the cases, and lacunar cells were seen in 12 cases. CONCLUSIONS The diagnostic efficacy of FNAC is much lower for grade 2 NSCHL versus grade 1 NSCHL. The search for an occasional RS cell and the identification of lacunar cells can provide a clue for the diagnosis. Cancer Cytopathol 2016. © 2016 American Cancer Society.

Syncytial variant of nodular sclerosis (SV-NS) classical Hodgkin lymphoma (cHL) with its histologic features and clinical presentation is uncommon in adults and extremely rare in children. Here, we report a female teenager presenting with long-standing B symptoms, prominent soft tissue and bone involvement mimicking sarcoma and significant nodal disease who is diagnosed with advanced SV-NS cHL. Rare Reed-Sternberg-like cells displaying neutrophil and erythrocyte emperipolesis were seen on bone marrow aspiration slides. Despite initial complete response to chemotherapy and radiotherapy, the patient experienced early relapse suggestive of high-risk biology. This variant may constitute a unique entity.

Classical Hodgkin lymphoma (cHL) is frequently related to Epstein-Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV-host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response. We explored the impact of four single nucleotide polymorphisms (SNPs) on EBV-associated cHL susceptibility. Toll-like receptors 9 (TLR9_rs5743836), and 3 (TLR3_rs3775291), Interleukin-28B (IL28B_rs12979860), and DEAD-box polypeptide 58 (DDX58_rs10813831) were genotyped in 73 EBV-positive and 106 EBV-negative cHL patients and 396 controls. Only DDX58_rs10813831 T-allele was decreased among EBV-positive cHL compared to controls. A stratified analysis in EBV-positive cHL showed that the reduced rate was associated with younger age and nodular sclerosis. In conclusion, DDX58_rs10813831 T-allele may be associated with a reduced risk of nodular sclerosis EBV-related cHL, which suggests a role for RIG-I (retinoic acid-inducible gene I), encoded by DDX58, in these cases.

A case of Hodgkin lymphoma located in the rectum of a patient with ulcerative colitis is described. The patient was a 44 year old male treated with thiopurines for ulcerative colitis for ten years. He was admitted with malaise, weight loss and abdominal pain. Endoscopy revealed a large ulcerative lesion involving the rectum and distal part of the sigmoid colon. Although it macroscopically resembled a rectal cancer, repeated biopsies did not reveal any malignancy. In order to resolve the symptoms of stenosis and to get the final diagnosis a recto-sigmoid resection was performed. Pathologic examination revealed nodular sclerosis classical Hodgkin lymphoma, positive for Epstein Barr Virus. Subsequent examination revealed disseminated disease involving the pelvic wall, liver, and bone marrow. The patient is currently receiving chemotherapeutic treatment, and follow-up shows disease remission. Hodgkin lymphoma associated with immunosuppressive therapy is rare. However, patients with ulcerative colitis receiving such treatment are at increased risk of lymphoproliferative disordes, potentially due to loss of immunosurveillance and presence of oncogenic viruses (i.e. Epstein-Barr virus). Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6156776351558952