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. 2023 Jul 5;12(13):1783. doi: 10.3390/cells12131783

Table 1.

Differential diagnostics of HD with subtypes, ALCL systemic vs. primary cutaneous, and MF CD30+.

Clinical Symptoms (Skin, Lymph Nodes, Internal Organs) Histopathology Immunohistochemistry
Lymphomas that affect the thymus (T-cell, B-cell lineages and Hodgkin lymphomas) Nodular Sclerosis (NS) (subtype of Hodgkin lymphomas—cHLs)

  • Enlarged lymph nodes, particularly in the neck, chest, or armpits;

  • Pain or discomfort in the affected lymph nodes after consuming alcohol.

  • B symptoms: Fever, night sweats, and unexplained weight loss.

  • Fatigue and general malaise.

  • Itchy skin (pruritus).
  • -

    large sclerotic masses with foci of necrosis and eosinophilic abscesses;

Reed–Sternberg cells (RS)
  • -

    large with abundant eosinophilic cytoplasm,

  • -

    large double or multiple nuclei, eosinophilic nucleoli;

Lacunar cells (LC)
  • -

    cells more frequently associated to cHL-NS;

  • -

    small hyperlobulated nuclei, small nucleoli;

  • -

    clear, retracted cytoplasm.

 CD30 + (85–96%, Memb + Golgi area)
CD15 + (75–85%)
CD20 + (<20–40%)
CD79a (Rarely+)
PAX5; OCT2; MUM1; EBER (EBV); LMP-1 (EBV)
Cyclin E
Fascin
PMBL (primary mediastinal B-cell lymphoma)

  • Limited to the thorax with no involvement of lymph nodes or other lymphoid organs (only supraclavicular nodes are eventually reached);

  • Chest pain or pressure due to the tumor’s location in the mediastinum;

  • Difficulty breathing or shortness of breath;

  • Coughing or wheezing.

 bulky, solid masses of >10 cm, with local symptoms of rapid growth, invasion,
and compression of vital structures.
Neoplastic cells
  • -

    variable size, sometimes with pale clear cytoplasm in the central part of the tumor;

  • -

    peripherally distributed lymphocytes in the sclerotic background.

 CD30 + (weakly or focally expressed, with lesser intensity than in cHL)
CD45
CD20
CD79a
PAX5; OCT2; BOB1; MUM1
MAL; CD23; BCL6; P63
T-lymphoblastic lymphoma (T-Lb)

  • Enlarged lymph nodes, commonly in the neck, chest, or armpits.

  • Swelling or mass in the thymus or mediastinum.

  • Difficulty breathing or shortness of breath.

  • Coughing or wheezing.
  • -

    thymic remnant and epithelial cell (EC) networks are rarely found;

  • -

    frequent mitosis and extensive necrosis.

 CD30 (rare)
T-cell markers: CD3, CD5, and CD7
TdT
CD1a; CD99; CD4 and CD8;
cyclin-dependent kinase-6 (CDK6)
B1—Thymoma

  • Asymptomatic: Many B1 thymomas are discovered incidentally during imaging studies performed for other reasons.

  • Chest pain or discomfort.

  • Coughing or respiratory symptoms (if the tumor compresses nearby structures).

  • Difficulty breathing or shortness of breath.
  • -

    EC network may partially be seen even in necrotic tumors;

  • -

    frequent mitosis and extensive necrosis

 (+) in >90%: CK5/6, CK7, CK8, CK18, CK19, p63
(+) in 50–90%: CD15, CD57 (leu7), PAX-8

Cytokeratins, CD30
ALCL Anaplastic large cell lymphoma, ALK positive
  • -

    involves both lymph nodes and extranodal sites (skin, bone, soft tissue, lungs, liver + rarely, gastrointestinal tract or central nervous system);
  • -

    chromosomal translocation involving ALK, leading to the expression of both ALK protein and CD30 proteins;

Tumor cells
  • -

    abundant cytoplasm that may appear clear, basophilic, or eosinophilic;

  • -

    multiple nuclei arranged in an arc-shaped configuration;

  • -

    nuclear chromatin tends to be finely clumped or dispersed, with multiple small, basophilic nucleoli.

Hallmark cells
  • -

    eccentric, horseshoe-shaped, or kidney-shaped nuclei that often exhibit an eosinophilic region near their nucleus;

  • -

    ample cytoplasm;

Doughnut cells
  • -

    invaginations of the nuclear membrane;

“Fried egg cells”
  • -

    small to medium-sized neoplastic cells with irregular nuclei, and pale cytoplasm and centrally located nuclei that have become cancerous over time

 (+) in >90%
ALK, CD30, clusterin, CD43,
cytotoxic molecules (TIA-1, perforin, granzyme B)
(+) in 50–90%
CD2, CD4, CD25, CD45, EMA, galectin-3
(+) in 10–50%
CD3, CD5, CD7, CD15, fascin, bcl-6
(+) in <10%
CD8, CD20, CD28, PAX-5
Anaplastic large cell lymphoma,
ALK negative
  • -

    affects both lymph nodes and extranodal tissues;

  • -

    extranodal involvement tends to be less frequent compared to ALK+ ALCL cases (bone, soft tissue, and skin);
  • -

    large lymphoid cells with horseshoe-shaped nuclei and ample cytoplasm;

  • -

    does not express detectable amounts of the ALK protein;

  • -

    similar features to ALCL ALK positive.

 (+) in >90%
CD30, clusterin, CD43,
cytotoxic molecules (TIA-1, perforin, granzyme B)
(+) in 50–90%
CD2, CD4, CD25, CD45, EMA, galectin-3
(+) in 10–50%
CD3, CD5, CD7, CD15, fascin, bcl-6
(+) in <10%
ALK, CD8, CD20, CD28, PAX-5
Mycosis fungoides
  • -

    in general => skin manifestations: initially are localized to sun-protected regions, then a combination of patches, plaques, and tumors +/− ulceration

  • -

    in advanced stages => extracutaneous sites (lymph nodes, liver, spleen, lungs, and bloodstream); +(rarely) the bone marrow.
  • -

    early stages: superficial infiltrates that resemble bands or lichen, mainly composed of lymphocytes and histiocytes;

  • -

    atypical cells, with highly indented (cerebriform) nuclei that are infrequent and mostly confined to the epidermis;

  • -

    Pautrier microabscesses (in a minority of cases).

 (+) in >90%
CD2, CD3, CD5, CD4, CD45RO
(+) in 10–50%
CD7. CD30
(+) in <10%
CD8, CD25