Nodular Sclerosis Classical Hodgkin Lymphoma (NSCHL)

At a Glance

Nodular sclerosis classical Hodgkin lymphoma (NSCHL) is the most frequent histologic subtype of classical Hodgkin lymphoma (CHL) in North America and Europe, comprising up to 70% of cases. It is seen mostly in young adults (peak incidence at 15-35 years of age) with approximately equal incidence in males and females. NSCHL is a less frequent CHL subtype in older adults, in immunosuppressed patients, and in developing countries.

Patients with NSCHL present most commonly with mediastinal disease that can be bulky and cause airway obstruction; however, superior vena cava syndrome is relatively uncommon, as compared with mediastinal large B-cell lymphoma, another lymphoma that also presents with a mediastinal mass. Systemic B symptoms are seen in less than one-half of NSCHL patients at presentation. Splenic involvement is uncommon, occurring in less than 10% of patients.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A biopsy of involved tissue should confirm a clinical suspicion of NSCHL.(Table 1)

Table 1.

Test Results Indicative of the Disorder
Tissue Biospy Immunohistochemistry on Tissue Biopsy
Presence of Reed-Sternberg cells and mononuclear variants (often including "lacunar cells" surrounded by a clear halo) in a mixed inflammatory background and bands of dense, collageous fibrosis delineating large tumor nodules. Reed-Sternberg cells and their mononuclear variants are CD30+, CD45-, usually CD15+, and PAX5+, but usually negative for other B-cell markers.

After diagnosis, the disease should be staged (see chapter on Classical Hodgkin Lymphoma).

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

As with all types of CHL, a fine needle aspiration, limited tissue biopsy, such as a core biopsy, or biopsy of a small, partially involved node may yield false-negative results in NSCHL.

In particular, because of the frequent mediastinal location of NSCHL, only limited core biopsies or small biopsies from mediastinoscopy may be obtained. These can result several diagnostic pitfalls. Partially involved or reactive nodes at the periphery of the neoplastic tumor mass may lead to a misdiagnosis as a reactive process. The dense sclerosis seen in NSCHL can yield biopsies that are crushed, and the diagnostic Reed-Sternberg cells may be poorly preserved. In such cases, it may be necessary to perform repeat biopsies from a more centrally located area of the tumor mass. Areas of necrosis may also be present, with limited or no viable tissue in the biopsy samples, precluding a definitive diagnosis; rebiopsy is also necessary in such cases.

Primary mediastinal large B-cell lymphoma (PMBL) also presents in the mediastinum of young adults, similar to NSCHL. In small tissue biopsies, these two entities may be difficult to distinguish; this distinction is important, as PMBL and NSCHL are treated differently. Unlike the Reed-Sternberg cells of NSCHL, the large neoplastic cells in PMBL are relatively frequent and strongly express CD20 and other B-cell markers but are CD15 negative. CD30 can also be expressed in PMBL but tends to be expressed more weakly and variably than the uniform, strong expression seen in the Reed-Sternberg cells of NSCHL.

What Lab Results Are Absolutely Confirmatory?

A biopsy of involved tissue confirms a diagnosis of NSCHL. Subtyping of CHL may be difficult on a limited biopsy; a diagnosis of NSCHL requires identification of bands of collagenous fibrosis surrounding the cellular tumor nodules. The latter are composed of the neoplastic Reed-Sternberg cells set in a mixed variable inflammatory background.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Unlike the mixed cellularity and lymphocyte-depleted types of CHL, Epstein-Barr virus (EBV) positivity of Reed-Sternberg cells, as detected by EBV-encoded RNA (EBER) in situ hybridization or EBV latent membrane protein (LMP1) immunohistochemistry is relatively infrequent in NSCHL, occurring in only 20-30% of cases.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Prior treatment with steroids may make the pathologic changes of NSCHL less marked and cause difficulties in diagnosis or misdiagnosis as a reactive process.

Some cases may show overlapping features of NSCHL and primary mediastinal large B-cell lymphoma, often with co-expression of CD20 and CD15. A new category of "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma" (so-called "mediastinal grey-zone lymphoma") has been recognized in the 2008 World Health Organization (WHO) Classification of Lymphoid Tumours to encompass such cases. Mediastinal grey-zone lymphomas display aggressive clinical behavior.

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