The newly developed and more sophisticated techniques for
analysis of lymphoma cells have provided us with the tools necessary for
precise classification of non-Hodgkin’s lymphoma. Nonetheless, routine
histologic studies remain the gold standard for diagnosis.
Excisional Biopsy
A well-processed hematoxylin and eosin (H&E) stained
section of an excised lymph node is the mainstay of pathologic diagnosis. Most
often, the diagnosis of difficult lesions relies heavily on a careful
assessment of the underlying architecture. Lymphoma diagnoses are much less
about cytologic detail and far more about altered architecture. For example,
follicular small-cleaved cell lymphoma (FSC) is characterized by an abundance
of neoplastic lymphoid follicles containing monomorphous small-cleaved
lymphocytes. The individual cells themselves, however, are otherwise typical
small cleaved lymphocytes seen in the benign follicles of reactive lymph nodes.
The loss of normal nodal architecture that accompanies an
infiltrate is of paramount importance in making a diagnosis. An incisional
lymph node provides only a glimpse of the architecture, making interpretation
difficult. Our surgical colleagues must be instructed to biopsy the most
clinically significant site, and whenever possible, to remove an intact lymph
node for pathological processing. The tissue should be delivered fresh to
pathology at an appropriate time of the day in order to maximize the material
for lymphoma protocol studies.
Many hematopathologists prefer to triage the material using
imprint preparations, whereby a fresh cut surface of the node is touched onto
glass slides for Romanowsky staining. Experienced pathologists are able to make
a good approximation of the disease process based on the touch prep morphology,
thus resulting in the efficient ordering of additional tests.
When the size of the tissue is limiting, the first priority
must be to process the material routinely for fixation and H&E sections.
Properly fixed specimens can be used for regular histologic examination,
paraffin(Drug information on paraffin) section immunoperoxidase staining, and
depending on the fixative, for gene rearrangement studies by polymerase chain
reaction (PCR). Although B5 is the optimal fixative for routine lymphoid
histology and is preferred for immunoperoxidase studies, it precludes PCR
studies in most laboratories. Formalin fixation is preferred when the biopsy is
small because all of the above studies, including PCR, can be performed.
Diagnosing Disease at Extranodal Sites—Approximately 30% to
35% of cases of non-Hodgkin’s lymphoma in adults present primarily at
extranodal sites. Much less is known about the molecular mechanisms involved in
these disorders in comparison to node-based disease. Therefore, it is important
to remember to process extranodal biopsy material for lymphoma protocol studies
whenever there is a suspicion of a hematolymphoid neoplasm.
Molecular genetic and cytogenetic data from gastric and
pulmonary resection specimens have enormous potential to provide insights into
the pathogenesis of mucosal-associated lymphoid tissue (MALT) lymphomas but,
unfortunately, lymphoma protocol is frequently overlooked in this setting.
Nonetheless, examination of a well-processed H&E section from an excisional
biopsy by an experienced hematopathologist will be sufficient to establish a
diagnosis in the majority of cases.
Needle-Core Biopsy & FNAC
Needle-core biopsies have a role in lymphoma pathology,
although it remains limited.The use of 14 to 22 gauge needles under ultrasound or
radiological guidance to establish a diagnosis of non-Hodgkin’s lymphoma is
problematic because of technical difficulties with biopsy crush artifact,
inadequate sampling, and the usual vagaries of lymphoma pathology. Although
this technique has advantages over fine-needle aspiration (FNA), it should be
used judiciously as a diagnostic tool for patients with suspected non-Hodgkin’s
lymphoma.
Needle-core biopsies do allow a minimal assessment of
architecture in addition to immunostaining procedures, but interpretation can
be problematic in cases of T-cell rich B-cell lymphoma, angioimmunoblastic-type
peripheral T-cell lymphoma, or MALT lymphoma where much of the lymphoid
infiltrate is reactive.
A careful review of most excisional lymph node biopsies
demonstrates marked cytologic and architectural variation throughout the
section, underscoring the complexity of non-Hodgkin’s lymphoma diagnoses in
what would otherwise be considered routine circumstances.
Needle-core biopsies are unable to detect this variability,
leading to the possibility of incorrect diagnoses in many cases. Although
recent studies have recommended increased use of these techniques, patient
selection and failure to provide convincing evidence that the “right treatment”
decision was made in the majority of cases hamper their interpretation. Also,
many of these studies included patients with an established diagnosis of either
non-Hodgkin’s lymphoma or Hodgkin’s disease—an approach that differs
significantly from a diagnostic procedure.
In managing ill patients or those with significant comorbid
disease who are unable to tolerate an invasive surgical procedure, needle-core
biopsies offer a better alternative to FNA for the diagnosis of intra-abdominal
or thoracic disease. Ideally, two or three cores should be obtained with one
core routinely processed for histology and the remainder used for lineage and
clonality studies. In this setting, cautious interpretation of the biopsy by an
experienced hematopathologist and integration of the results of the ancillary
studies should allow a reasonable treatment decision to be made in most cases.
