Case History
The patient is a 54 year old woman who presented to the hospital after a fall, which revealed a pathologic fracture of T1 and a spinal lesion from C6/C7 to T2. CT of the chest/abdomen and pelvis at the time showed a large mass in the anterior mediastinum with extensive lymphadenopathy and lytic lesions in the spine and ribs.
C7-T1 Soft Tissue Excision
Diagnosis
Sections show sheets of large epithelioid-like cells with segmented nuclei with variably prominent nucleoli and ample amounts of eosinophilic cytoplasm.A majority of these larger cells have abundant cytoplasm and lobulated nucle iwith multiple nucleoli and a surrounding halo. They are consistent with Lacunar cells. These cells form large aggregates and are admixed with numerous neutrophils, histiocytes and scattered lymphocytes.
Occasional Hodgkin cells and multi-nucleated Reed-Sternberg cells are seen, as well as scattered medium size hyper chromatic cells with irregular nuclear contours and scant cytoplasm consistent with mummy cells.
Immunohistochemical staining revealed that the largea typical cells are immunoreactive for CD30, CD15 and PAX5/BSAP. CD45 highlighted background lymphocytes but showed infrequent dim staining in the large atypical cells. By Ki-67, the proliferation index is 50-60% in the large atypical cells. Taken together, the findings are consistent with Classic Hodgkin Lymphoma, nodular sclerosis, syncytial variant.
Discussion
Classic Hodgkin lymphoma (CHL) has four distinct subtypes including nodular sclerosis, lymphocyte-rich, mixed cellularity and lymphocyte-depleted. These subtypes differ based on characteristics of the background non-neopalastic reactive cells and the histomorphology of the Hodgkin/Reed-Sternberg cells (HRS). Nodular sclerosis Classic Hodgkin lymphoma accounts (NSCHL) for approximately 70% of all CHLs. The mediastinum is the most commonly involved site and it generally occurs in people between the ages of 15-34 years old. Generally, the histology shows nodules with surrounding fibrosis. There are a variable number of Hodgkin/Reed-Sternberg (HRS) cells mixed with other inflammatory cells. The characteristic HRS cell is called a lacunar cell. This is a type of HRS cell with more cytoplasm, less prominent nucleoli and can show retraction of the cytoplasm in formalin-fixed tissue that gives the cell a halo or “lacunae.”1
The syncytial variant (SV) of CHL, nodular sclerosis was first described in the 1980s. It presents in 5-15% of cases of NS CHL. It is characterized by sheets and clusters of “lacunar cells” typical of the type of HRS cell most commonly seen in NS CHL. Previous studies had determined the SV of CHL to have a worse prognosis and more aggressive course than other subgroups. In a more recent study by Sethi, et. al. the clinical features and response to treatment of patients with SV were compared to patients with typical NS CHL. Within the cohort, 43 patients with SV were compared to 124 patients with typical NS CHL. The study found that there was no significant difference in age, sex, performance status, stage, bulky disease, number of nodal sites and chemotherapy regimens used between the two groups.2
As far as treatment outcomes, the rate of complete response in the SV group was 74% vs. 87% in the NS group. This result approached statistical significance with a p=0.05. The medium progression-free survival in the SV group was significantly shorter compared with the NS group. The overall survival, however was not statistically different, indicating that salvage chemotherapy was ultimately able to match the clinical outcomes for patients with SV type to patients with NS type. 2
Currently, all CHLs are treated with adriamycin, bleomycin,vinblastine, decarbazine (ABVD) chemotherapy regimen plus or minus radiation therapy regardless of subtype. Patients with relapsed or refractory disease are treated with a “salvage” chemotherapy regimen followed by an autologous stem cell transplant. Emerging therapies including PD-1 inhibitor nivolumab have shown great effect in patients with CHL. PD-1 or programmed death ligand 1 is overexpressed on HRS cells. This ligand binds with receptorson T-cells to prevent the T-cell immune response and reduce cytokine activation and targeted response against the proliferating HRS cells. By using an antibody against the PD-1 ligand in CHL,the ability of the tumor to suppress the immune response is decreased and patients have been shown to have better clinical response rates.3
Patients with SV do need to be recognized as a distinct subgroup that may have a higher risk of disease progression with first line chemotherapy agents. Due to the high numbers of HRS cells seen in patients with SV and the increased failure rate of initial chemotherapy agents, antibody therapies such as PD-1 inhibitors may be even more successful in those patients.
References
- Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues (Revised 4thedition). IARC: Lyon 2017.
- Sethi, T.K., et al. Differences in Outcome of Patients with Syncytial Variant Hodgkin Lymphoma (HL) Compared with Typical Nodular Sclerosis HL. Blood. 2015;126(23),1441. Retrieved from http://www.bloodjournal.org/content/126/23/1441.
- Bond DA, Alinari L. Emerging treatment options for the management of Hodgkin’s lymphoma:clinical utility of nivolumab. J Blood Med. 2017;8:41-54. Published 2017 May 11. doi:10.2147/JBM.S117452.
–Chelsea Marcus, MD is a third year resident in anatomic and clinical pathology at Beth Israel Deaconess Medical Center in Boston, MA and will be starting her fellowship in Hematopathology at BIDMC in July. She has a particular interest in High-grade B-Cell lymphomas and the genetic alterations of these lymphomas.
Lablogatory 