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淋巴瘤 - Slide seminar-Guangzhou-2008-Chan


更新时间:2008-07-25 10:47:42 作者: 陈国璋




Case 3
F/22
Left breast “abscess” and left axillary mass
Both masses were excized

Immunohistochemistry
Negative with a first-tier panel of CD20 and CD3
CD56 also negative
Not a lymphoma?
An unusual form of lymphoma?
Anaplastic large cell lymphoma
Plasmablastic neoplasm (including ALK+ large B cell lymphoma)

Diagnosis (Case 3)
Anaplastic large cell lymphoma,
primary systemic form, ALK+,
classical, with focal features of lymphohistiocytic and hypocellular variants

Partner genes fused with ALK in ALCL

Translocation Partner gene ALK staining Frequency
t(2;5) NPM Nuclear and cytoplasmic 70-80%
t(1;2) TPM3 Cytoplasmic 10-20%
t(2;3) TFG Cytoplasmic 2-5%
Inv2 ATIC Cytoplasmic 2-5%
t(2;17) Clathrin Granular 2-5%
t(X;2) Moesin Cell membrane ?

Revised morphologic spectrum of ALCL
Using ALK as a defining feature, the morphologic spectrum of ALCL has broadened
Some cases previously not considered to be within the spectrum of ALCL (not “anaplastic-looking” and simply classified as peripheral T cell lymphoma unspecified) are now recognized as belonging to this biologic entity

Hallmark cells for diagnosis of ALCL
Large or medium-sized cell
Embryo-like nucleus
Usually multiple nucleoli rather than single prominent nucleolus
Prominent Golgi zone in the voluminous amphophilic cytoplasm (producing a plasmacytoid appearance)

Revised morphologic spectrum of ALCL
Common type:
Many hallmark cells
Some cells have wreath-like nuclei
May have admixed inflammatory cells
Sinusoidal pattern is common

Revised morphologic spectrum of ALCL
Common type with morphologically deceptive features:
Growth in cohesive nodules
Growth in trabeculae
Myxoid stroma
Spindly cells (sarcomatoid)
Neutrophil-rich (mimicking inflammatory process)


Revised morphologic spectrum of ALCL
Monomorphic type:
Medium-sized to large cells
Often giving an impression of cellular monotony
Hallmark cells present, but may have to search for them


Revised morphologic spectrum of ALCL
Lymphohistiocytic type:
Often mistaken for reactive lymphoid hyperplasia
Reactive background including many lymphocytes and histiocytes with peculiar plasma cell-like morphology
The neoplastic lymphoid cells (medium-sized or large) that are interspersed are often obscured by the background lymphocytes and histiocytes

Revised morphologic spectrum of ALCL
Small cell type:
Often mistaken for reactive lymphoid hyperplasia
Small cells are neoplastic (with irregular nuclear foldings)
Scattered larger CD30+ “hallmark” cells
Large cells are accentuated around blood vessels
More likely than other subtypes to become leukemic
May transform to frank ALCL (classic or monomorphic)

Revised morphologic spectrum of ALCL
Hypocellular variant:
Very low cellularity and edema, mimicking inflammatory or reparative lesion
Wide separation of small to medium-sized cells (resembling histiocytes) by edematous or fibromyxoid stroma
Interspersed spindly tumor cells, resembling myofibroblasts
Larger cells tend to form cuffs around venules


Have a high index of suspicion for ALK+ anaplastic large cell lymphoma in children and
young adults! Perform CD30 and ALK immunostains liberally for any unusual-looking tumors or unusual lymphoid cell proliferations in such age group.

Case 4
M/19
Presented with sore throat
Tonsils were markedly enlarged and ulcerated

Diagnostic considerations
Increased large lymphoid cells (not frankly atypical)
Germinal centers show depletion of lymphoid cells
Reactive lymphoid hyperplasia?
Lymphoma?

Diagnosis (Case 4)
Tonsil – Infectious mononucleosis

INFECTIOUS MONONUCLEOSIS
The marked increase in large lymphoid cells can easily entice the pathologist to render a wrong diagnosis of lymphoma

A wrong diagnosis can be disastrous,because these young patients will be subjected to unnecessary cytotoxic therapy –Potential for litigation

Infectious mononucleosis: Pathology
Distortion or subtotal effacement of architecture
Residual germinal centers often show necrosis
Lymph node: sinuses often patent and contain large lymphoid cells
Tonsils: Prominent ulceration and necrosis
Many large activated lymphoid cells

Features favoring a benign process in a prominent immunoblastic proliferation
Young age
Some residual normal lymphoid architecture, e.g. focal preservation of sinuses, necrosis of germinal centers
Lack of significant atypia in large cells
Polymorphous appearance of large cells, with apparent maturation to plasmablasts and plasma cells (spectrum of B cells)

Making a diagnosis of infectious mononucleosis
High index of suspicion is required!
Seriously consider this possibility for any young patient suspected of having a large cell lymphoma on morphologic evaluation

Case 7
M/73
Chinese
Presented with perforation of small bowel
Gross specimen: 15 cm of small bowel resected, with central irregular area of perforation; mucosa edematous; wall slightly thickened

Diagnosis (Case 7)
Small bowel –
Enteropathy-type T-cell lymphoma,
monomorphic subtype, CD56+

ENTEROPATHY-TYPE T-CELL LYMPHOMA
A tumor of intestinal intraepithelial T lymphocytes
Presentation: small intestinal mass/ulcer, often multifocal. Intestinal perforation, obstruction or hemorrhage.
Relationship with celiac disease
Long history
Short history of adult celiac disease
History of dermatitis herpetiformis
No history of celiac disease

Enteropathy-type T cell lymphoma: Pathology
Cytology: Usually large cells, but can be small or medium-sized
Epitheliotropism is common
Some cases may have many admixed eosinophils and histiocytes
Surrounding mucosa: villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (i.e. features of celiac disease)

Enteropathy-type T cell lymphoma: Immuno-genetic features
T-lineage markers positive, but CD5 often -
CD103+ (marker for intraepithelial T lymphocyte)
Commonly CD4- CD8-, but some are CD8+
CD56 can be positive (usually monotonous medium-sized cells, and often CD8+)
EBV negative

Two histogenetic types of enteropathy-type T-cell lymphoma

  CD56+ CD56-
Frequency 20% 80%
Monomorphic histology 73% 7%
Clinical evidence of celiac disease 0% 32%
Enteropathy histology 50% 85%
CD8+ 80% 19%
  CD56+ CD56-
+9q 67% 67%
+8q24 73% 27%
+1q32-q41 20% 73%
+5q34-q35 20% 80%
Celiac disease-associated HLA haplotype 50% 90%

Practically never seen in Asians!

Case 8
F/34
Presented with abdominal pain
Examination showed marked splenomegaly and pancytopenia
Spleen was removed: 2.33 Kg, with beefy red cut surface studded with numerous small white dots

Case 8: Analysis
Spleen shows micronodular pattern of involvement
Composition of micronodules:
Small lymphocytes
Solitary epithelioid histiocytes
Scattered large cells: mostly non-atypical, only rare ones show atypical nuclei

Diagnosis (Case 8)
Spleen – T-cell/histiocyte-rich large B-cell lymphoma

Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen, Dogan A, et al. Am J Surg Pathol 2003;27:903-911
Patients usually present with splenomegaly but minimal or no lymphadenopathy
B symptoms are common
Median age: 56 years
Often show other sites of involvement, e.g. bone marrow, liver
Poor prognosis (7/12 patients dead within 2 yrs)

Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen, Dogan A, et al. Am J Surg Pathol 2003;27:903-911
Neoplastic large B cells often positive for Bcl-6, but not CD138 and EBV
No follicular dendritic cell meshworks underlying the micronodules
Often misdiagnosed as granulomatous inflammation, Hodgkin lymphoma, follicular lymphoma or peripheral T-cell lymphoma

Immunostaining for immunoglobulin
This can be successful performed and interpretable in most cases, especially in lesions rich in large cells (immunoblasts) and plasma cells
Sometimes this is the most important stain for distinguishing between reactive lymphoid hyperplasia and B-cell lymphoma

Immunostaining for immunoglobulin
Immunostaining protocol:
Heat-induced antigen retrieval using citrate buffer pH 6.0
Polyclonal antiserum against kappa and lambda light chains from Dako (dilution 1: 48,000)
Use Polymer detection system



 

 

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