血液腫瘍病理学

Diffuse large B-cell lymphoma(DLBCL) びまん性大型B細胞リンパ腫

 
DLBCL35.jpg

DLBCLは悪性リンパ腫のなかでも最も頻度の高い病型(図; 古くなった統計であるが)で, 現在 Non-Hodgkin lymphoma診断の約30〜40%を占めている.

臨床的には中悪性度(治療を行わない/治療が奏功しない場合, 月単位で進行悪化)あるいは高悪性度(同じく週単位で進行悪化する)リンパ腫であり, 急速な腫瘍の進展があるため診断後早期の治療介入が必要となる.

大細胞の定義は, 組織内に存在する小リンパ球とくらべて2倍以上の大きさ (以前はいろんな細胞;内皮や組織球など,と比べる説があったが今はこれ)

DLBCLは生物学的, 形態学的, 遺伝学的および臨床的に非常に不均一で多彩な疾患単位である.
近年の遺伝子発現解析により2つの大きなsubtypeに分類された. さらにNGSを用いた網羅的遺伝子解析により特徴的な遺伝子異常をもつ臨床的また分子病態が異なる4から5個群のグループに再分類され, 将来的な個別化医療の適応への応用が期待されている.

WHO 4th revised*1

→ 個々の疾患亜型における詳細を記載

→DLBCLの個別化

→ grey zone lymphomaの理解;intermediate typeを廃止, high-grade B-cell lymphomaの疾患単位を樹立.

→ 新規治療戦略

 

DLBCLの臨床像

  • 発症年齢中央値は 60歳代, 小児やAYA世代にも発症する. やや男性に多い
     
  • 急速に進行するが, 化学療法に対する反応性は良好で約半数以上が治癒可能である.
     
  • 治療反応性, 予後, 細胞形態, 生物学的特性などがさまざまな不均一な疾患群
     
  • 急速なリンパ節腫大. 無症状もあるが, B症状(発熱, 体重減少, 盗汗など)は30〜40%の患者さんに観察される. LDHは半数例で上昇する.*2*3
     
  • 約40〜50%が節外臓器から発症する.
  • 最も多い節外病変は胃, 消化管*4*5*6であるが, 睾丸*7, 骨, 甲状腺, 唾液腺*8, 扁桃*9*10*11, 皮膚*12, 肝臓*13, 乳房*14*15*16, 副腎, *17*18, 鼻腔*19*20, *21
    眼付属器*22, 副鼻腔*23, 子宮頸部*24, 膣*25, 中枢神経*26など, どの部位にも発生しうる*27.

DLBCL, Not Otherwise Specified

Common morphologic variants (* それぞれの特徴をもつ細胞が90%以上を占める病変に用いる)

Centroblastic (胚中心芽球型)
Immunoblastic (免疫芽球型)
Anaplastic (退形成/ 未分化細胞型)
Rare morphologic variants

Centroblastic および immunoblastic variantが通常多く認められる他に, multilobulatedや anaplastic variantが認められている,しかし, これら細胞形態による臨床的意義については評価が定まっていない.*28

DLBCL_centroblastic02.jpg(235.7KB) DLBCL_centroblastic01.jpg(170.2KB)DLBCL centroblastic variant (サムネイルのクリックで大きな画像が見られます)

Centroblastic variant(胚中心芽球型)

  • 最も多くみられるtype.腫瘍細胞は胚中心, centroblastに似る. (核膜に付着するように核小体が2〜4個認められる)
  • 核はほぼ均一な大きさのことが多いが, ときに大小不同がめだつこともある.まれに分葉ないし多核に見える細胞が混在.
    免疫芽球が混在することもある.
  • 分葉構造がめだつことがあり, 節外性に多い. GCBが多い.

DLBCL_immunoblastic01.jpg(208.5KB) DLBCL_immunoblastic02.jpg(159.4KB) ← DLBCL immunoblastic variant

DLBCL_anaplastic00.jpg(186.0KB) DLBCL_anaplastic02.jpg(164.8KB) ← DLBCL anaplastic variant

 

血液病理学者が腫瘍細胞形態に基づいてDLBCLをサブタイプ化しようと試みたが,観察者および観察者群間の再現性が乏しく, 結果として, WHOリンパ性腫瘍組織分類においてDLBCLとして単一の診断カテゴリーにまとめられている.*29

 

Molecular subgroupe

Germinal cener B-cell-like Activated B-cell-like

Immunohistochemical subgroups

CD5+ DLBCL
Germinal center B-cell-like
Non-germinal center B-cell-like

DLBCL Subtypes

T-cell/ histiocyte-rich B-cell lymphoma
Primary DLBCL of the central nervous system
Primary cutaneous DLBCL, leg type
EBV+ DLBCL of the elderly→→WHO 4th revisedでは EBV-positive diffuse large B-cell lymphoma, NOS

Other lymphoma of Large B Cells Primary mediastinal(thymic) large B-cell lymphoma
Intravascular large B-cell lymphoma
DLBCL associated with chronic inflammation
Lymphomatoid granulomatosis
ALK+ large B-cell lymphoma
Plasmablastic lymphoma
Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease
Primary effusion lymphoma
HHV8- and EBV-associated germinotropic lymphoproliferative disorder( not listed in the WHO classification)

High-grade B-cell lymphoma(新疾患単位として記載)

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement-->High-grade B-cell lymphomaのページをみる.
High-grade B-cell lymphoma, NOS

  • B-cell lymphoma, unclassifiale, with features intrmediate between DLBCL and Burkitt's lymphoma → WHO 4thでは削除されて新疾患単位になった.

B-cell lymphoma, unclassifiable
B-cell lymphoma, unclassifiale, with features intrmediate between DLBCL and classical Hodgkin's lymphoma


*1  Swerdlow SH, Campo E, Harris N, et al.(eds.): WHO classification of Tumours of Haematopoietic and Lymphoid Tissues, revied 4th ed., IARC Press, Lyon, 2017
*2  Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998; 16:2780.
*3  A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997; 89:3909.
*4  Aviles A, Neri N, Huerta-Guzman J. Large bowel lymphoma: an analysis of prognostic factors and therapy in 53 patients. J Surg Oncol 2002; 80:111.
*5  Daum S, Ullrich R, Heise W, et al. Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma. J Clin Oncol 2003; 21:2740.
*6  Ferrucci PF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years? Br J Haematol 2007; 136:521.
*7  Seymour JF, Solomon B, Wolf MM, et al. Primary large-cell non-Hodgkin's lymphoma of the testis: a retrospective analysis of patterns of failure and prognostic factors. Clin Lymphoma 2001; 2:109.
*8  Olivier KR, Brown PD, Stafford SL, et al. Efficacy and treatment-related toxicity of radiotherapy for early-stage primary non-Hodgkin lymphoma of the parotid gland. Int J Radiat Oncol Biol Phys 2004; 60:1510.
*9  Laskar S, Bahl G, Muckaden MA, et al. Primary diffuse large B-cell lymphoma of the tonsil: is a higher radiotherapy dose required? Cancer 2007; 110:816.
*10  de Leval L, Bonnet C, Copie-Bergman C, et al. Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study. Ann Oncol 2012; 23:3143.
*11  Vitolo U, Ferreri AJ, Zucca E. Primary testicular lymphoma. Crit Rev Oncol Hematol 2008; 65:183.
*12  Grange F, Bekkenk MW, Wechsler J, et al. Prognostic factors in primary cutaneous large B-cell lymphomas: a European multicenter study. J Clin Oncol 2001; 19:3602.
*13  Page RD, Romaguera JE, Osborne B, et al. Primary hepatic lymphoma: favorable outcome after combination chemotherapy. Cancer 2001; 92:2023.
*14  Ribrag V, Bibeau F, El Weshi A, et al. Primary breast lymphoma: a report of 20 cases. Br J Haematol 2001; 115:253.
*15  Domchek SM, Hecht JL, Fleming MD, et al. Lymphomas of the breast: primary and secondary involvement. Cancer 2002; 94:6.
*16  Aviles A, Delgado S, Nambo MJ, et al. Primary breast lymphoma: results of a controlled clinical trial. Oncology 2005; 69:256.
*17  Grigg AP, Connors JM. Primary adrenal lymphoma. Clin Lymphoma 2003; 4:154.
*18  Kuo CC, Li WY, Huang CC, et al. Primary renal lymphoma. Br J Haematol 2009; 144:628.
*19  Shikama N, Ikeda H, Nakamura S, et al. Localized aggressive non-Hodgkin's lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group. Int J Radiat Oncol Biol Phys 2001; 51:1228.
*20  Proulx GM, Caudra-Garcia I, Ferry J, et al. Lymphoma of the nasal cavity and paranasal sinuses: treatment and outcome of early-stage disease. Am J Clin Oncol 2003; 26:6.
*21  Lu NN, Li YX, Wang WH, et al. Clinical behavior and treatment outcome of primary nasal diffuse large B-cell lymphoma. Cancer 2012; 118:1593.
*22  Munch-Petersen HD, Rasmussen PK, Coupland SE, et al. Ocular adnexal diffuse large B-cell lymphoma: a multicenter international study. JAMA Ophthalmol 2015; 133:165.
*23  Oprea C, Cainap C, Azoulay R, et al. Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses: a report of 14 cases. Br J Haematol 2005; 131:468.
*24  Dursun P, Gultekin M, Bozdag G, et al. Primary cervical lymphoma: report of two cases and review of the literature. Gynecol Oncol 2005; 98:484.
*25  Guastafierro S, Tedeschi A, Criscuolo C, et al. Primary extranodal non-Hodgkin's lymphoma of the vagina: a case report and a review of the literature. Acta Haematol 2012; 128:33.
*26  Monnard V, Sun A, Epelbaum R, et al. Primary spinal epidural lymphoma: patients' profile, outcome, and prognostic factors: a multicenter Rare Cancer Network study. Int J Radiat Oncol Biol Phys 2006; 65:817.
*27  Castillo JJ, Winer ES, Olszewski AJ. Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database. Am J Hematol 2014; 89:310.
*28  De Paepe P, Achten R, Verhoef G, et al. Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas. J Clin Oncol 2005; 23:7060.
*29  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition, Swerdlow SH, Campo E, Harris NL, et al. (Eds), International Agency for Research on Cancer (IARC), Lyon 2017.

添付ファイル: fileDLBCL_immunoblastic02_s.jpg 10件 [詳細] fileDLBCL_immunoblastic02.jpg 24件 [詳細] fileDLBCL_immunoblastic01_s.jpg 14件 [詳細] fileDLBCL_immunoblastic01.jpg 24件 [詳細] fileDLBCL_centroblastic02_s.jpg 11件 [詳細] fileDLBCL_centroblastic02.jpg 21件 [詳細] fileDLBCL_centroblastic01_s.jpg 9件 [詳細] fileDLBCL_centroblastic01.jpg 24件 [詳細] fileDLBCL_anaplastic02_s.jpg 8件 [詳細] fileDLBCL_anaplastic02.jpg 22件 [詳細] fileDLBCL_anaplastic01_s.jpg 11件 [詳細] fileDLBCL_anaplastic01.jpg 10件 [詳細] fileDLBCL_anaplastic00_s.jpg 9件 [詳細] fileDLBCL_anaplastic00.jpg 22件 [詳細] fileDLBCL35.jpg 23件 [詳細]

トップ   編集 凍結 差分 バックアップ 添付 複製 名前変更 リロード   新規 一覧 単語検索 最終更新   ヘルプ   最終更新のRSS
Last-modified: 2019-06-03 (月) 13:07:30 (78d)