Esophagus
Other malignancies
Lymphoma

Author: Feriyl Bhaijee, M.D. (see Authors page)
Editor: Israh Akhtar, M.D.

Revised: 31 January 2018, last major update November 2013

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Lymphoma[TI] esophagus[TI]

Cite this page: Bhaijee, F. Lymphoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/esophaguslymphoma.html. Accessed February 24th, 2018.
Definition / general
  • Lymphomas comprise a diverse group of clonal (malignant) lymphoproliferative disorders, classified by WHO based on lymphocytic origin (lymphoma)
    • Hodgkin lymphomas arise from precursor B cells (Reed-Sternberg cells)
      • Classic Hodgkin lymphoma - 95%
      • Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) - 5%
    • Non-Hodgkin lymphomas arise from monoclonal expansion of malignant B or T cells
      • B cell lymphomas
        • B cell acute lymphoblastic lymphoma (ALL)
        • Chronic lymphocytic lymphoma / small lymphocytic leukemia (CLL / SLL)
        • Mantle cell lymphoma
        • Follicular lymphoma
        • Marginal zone B cell lymphoma
        • Extranodal MALT type
        • Hairy cell leukemia
        • Plasmacytoma / plasma cell myeloma
        • Diffuse large B cell lymphoma (DLBCL)
        • Burkitt lymphoma
      • T / NK cell lymphomas
        • T cell acute lymphoblastic lymphoma (ALL)
        • T cell CLL
        • Mycosis fungoides / Sézary syndrome
        • Peripheral T cell lymphoma
        • Angioimmunoblastic T cell lymphoma
        • Enteropathy associated intestinal T cell lymphoma
        • Hepatosplenic T cell lymphoma
        • Anaplastic large cell lymphoma (ALCL)
        • Extranodal NK / T cell lymphoma, nasal type
Terminology
  • Primary esophageal lymphoma
    • Arises de novo in esophageal mucosa associated lymphoid tissue (MALT)
  • Secondary esophageal lymphoma
    • Spreads to esophagus by either direct extension or metastasis
Epidemiology
  • GI tract is most common site of extranodal non-Hodgkin lymphoma (4 - 20%)
    • Esophagus is least common site of GI involvement
      • < 0.2% of all extranodal non-Hodgkin lymphoma
  • Lymphomas comprise < 1% of all esophageal cancers
    • Secondary lymphoma (contiguous spread from mediastinal or cervical lymph nodes) >> primary esophageal disease
    • Most originate from mature B cells
      • Non-Hodgkin lymphoma >> Hodgkin lymphoma
      • Mostly DLBCL and extranodal marginal zone B cell lymphoma, MALT type
  • Males > females
  • Wide age range: 17 - 86 years but usually middle age to older adults
    • Younger age of onset in HIV+ patients (40 vs. 60 years)
Sites
  • Primary lymphoma:
    • Arises in submucosal lymphoid patches
  • Secondary lymphoma
    • Proximal esophageal involvement may result from adjacent cervical lymphadenopathy
    • Middle esophageal involvement may be due to mediastinal lymphadenopathy
    • Distal esophageal involvement often secondary to gastric disease
Risk factors
  • Chronic immune suppression or dysregulation
    • HIV infection
    • Chronic hepatitis C infection
Clinical features
  • Features of primary lymphoma (Dawson criteria):
    • No palpable superficial lymphadenopathy
    • Normal chest radiograph with no evidence of lymphadenopathy
    • Normal peripheral white blood cell count
    • Primary esophageal lesion with only regional adenopathy
    • No liver or spleen involvement
  • Insidious onset
    • Dysphagia (most common)
    • Odynophagia
    • Chest / abdominal pain
    • Weight loss
  • Complications (Ann Otol Rhinol Laryngol 1994;103:843)
    • Hemorrhage
    • Vocal cord paralysis / hoarseness
    • Stricture / obstruction
    • Perforation with esophagomediastinal or esophagotracheobronchial fistula or mediastinitis
    • Vocal cord paralysis
  • Relatively poor prognosis
Diagnosis
  • Biopsy with ancillary studies (immunohistochemistry, flow cytometry) to confirm histologic type
Laboratory
  • Complete blood count may show:
    • Leukocytosis ± blasts (leukemic spread)
    • Pancytopenia (bone marrow infiltration)
Radiology description
  • Nonspecific radiographic features
  • Local extension of gastric lymphoma may cause distal esophageal stricture
  • Barium swallow / CT: stricture, polypoid or intramural mass
  • PET useful for staging
Radiology images

Images hosted on other servers:

Strictures:

Marked 3 cm narrowing

Irregular outline and multiple filling defects

Luminal narrowing



Esophageal thickening ± mass lesions:

4 x 4 cm esophageal mass

Thickening of the esophageal wall

Thickening the aortic arch to the gastrointestinal junction



Endoscopic ultrasound:

Transmural thickening of the esophageal wall

Hypoechoic thickening



Primary esophageal Hodgkin lymphoma:

Submucosal nodules

Circumferential thickening

Aneurysmal dilatation

Nodular thickening of esophageal wall

Fistula to lobectomy

Prognostic factors
  • Stage at diagnosis
  • Feasibility of surgery or chemotherapy
    • Successful management depends on accurate diagnosis and appropriate subsequent treatment
  • Histologic type: MALT lymphoma and Hodgkin lymphoma have better prognoses than DLBCL or T cell lymphomas
  • HIV / AIDS associated with worse outcomes
    • Median survival: 4 - 6 months
Case reports
Treatment
  • Primary esophageal lymphoma: local and systemic therapy
    • Radiotherapy, chemotherapy
      • Non-Hodgkin lymphoma: CHOP (cyclophosphamide, vincristine, prednisone, doxorubicin), rituximab (anti-CD20 monoclonal antibody)
      • Hodgkin lymphoma: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone)
    • Surgical resection: diagnostic, curative or palliative
  • Secondary esophageal lymphoma: chemotherapy
Clinical images

Images hosted on other servers:

Endoscopy:

Multiple solid, firm nodular lesions

Ulcerated tumor

Large, rounded mass

Solid, firm nodular lesions

Multiple lymphomatous polyposis

Gross description
  • Submucosal mass with variable ulceration or exophytic growth
Gross images

Images hosted on other servers:

Ulcerated burgeoning masses

MALT: esophagus /
proximal stomach
are unremarkable

Microscopic (histologic) description
  • DLBCL: large centrocytes, centroblasts, immunoblasts and anaplastic large B cells
    • Surface Ig+, CD20+, BCL6±, CD10±, CD43±, PAX5+
  • Marginal zone B cell lymphoma, MALT type: small lymphocytes, marginal zone B cells, plasma cells, reactive follicles, lymphoepithelial lesions
    • Surface and cytoplasmic Ig+ (IgM > IgG or IgA), CD20+, CD5-, CD10-, BCL6-, BCL2+, CD43±, cyclin D1-
  • Mantle cell lymphoma: small to medium sized, slightly irregular cells with scant cytoplasm
    • Surface IgMD+, CD20+, CD5+, CD10-, CD43+, cyclin D1+
  • Burkitt lymphoma: medium sized atypical lymphoid cells with round nuclei, basophilic cytoplasm and tingible body macrophages (starry sky appearance)
    • Cytoplasmic lipid droplets are Oil red O+
    • Surface IgM+, CD20+, CD10+, BCL6+, BCL2-, Ki67 ~100%
  • Follicular lymphoma: mixtures of centrocytes and centroblasts, follicular dendritic cells
    • Surface Ig+, CD20+, CD10+, BCL6+, BCL2+, CD5-, CD43-, cyclin D1-
  • Classic Hodgkin lymphoma: Reed-Sternberg cells and variants in a reactive background
    • R-S cells: CD30+, CD15±, PAX5+, ALK-, CD45-, CD3-
  • Nodular lymphocyte predominant Hodgkin lymphoma: vague nodules of small B cells and interspersed large tumor cells (LP cells) with thin nuclear membranes, fine chromatin and variable nucleoli
    • LP cells: CD45+, CD20+, CD15-, CD30-
Microscopic (histologic) images

Images hosted on other servers:

Diffuse large B cell lymphoma

Mantle cell lymphoma

Mantle cell lymphoma

Mycosis fungoides



MALT lymphoma:

Dense submucosal lymphocytic infiltrate

Vaguely nodular growth pattern

Monocytoid appearance

Germinal centers


CD20+

CD20+

BCL6+ in germinal centers

BCL6+


CD10

Ki67

Kappa / lambda

Cytology description
  • Discohesive, single abnormal lymphoid cells
Cytology images

Images hosted on other servers:

DLBCL

Burkitt lymphoma

MALT lymphoma

Peripheral smear description
  • Peripheral blasts if leukemic spread
Positive stains
  • CD45 (leucocyte common antigen): most hematopoietic neoplasms
    • Notable exceptions: ALCL, classic Hodgkin lymphoma, plasma cell myeloma
  • CD2, CD3, CD4: most T cell neoplasms
  • CD5: CLL / SLL, mantle cell lymphoma
  • CD10: follicular lymphoma, Burkitt lymphoma, some DLBCL
  • CD19, CD20, CD79a: most B cell neoplasms
  • CD23: SLL / CLL
  • CD30: ALCL, classic Hodgkin lymphoma
  • Cyclin D1: mantle cell lymphoma
  • EBV: classic Hodgkin lymphoma
  • EMA: ALCL, plasmacytoma, LP cells in NLPHL, some T cell lymphomas
  • MUM1: classic Hodgkin lymphoma, plasmablastic lymphoma
  • PAX5: B cell marker, classic Hodgkin lymphoma
Negative stains
Flow cytometry description
  • Useful to determine surface and cytoplasmic CD markers
Molecular / cytogenetics description
  • Common genetic features of mature B cell lymphomas
    • Marginal zone B cell lymphoma, MALT type
      • IGH clonally rearranged
      • t(11;18)
    • DLBCL
      • IGH clonally rearranged
      • t(8;14) c-myc-IGH
      • t(14;18) IGH-BCL2
    • Burkitt lymphoma
      • IGH clonally rearranged
      • t(8;14)
      • t(2;8)
      • t(8;22)
    • Mantle cell lymphoma
      • IGH clonally rearranged
      • t(11;14) BCL1-IGH
Differential diagnosis