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Sarcoidosis &
Cancer
Giulio Rossi
Anatomia Patologica
Azienda Policlinico di
Modena
[email protected]
Sarcoidosis
• Sarcoidosis is a systemic inflammatory disorder
of unknown etiology, characterized
pathologically by noncaseating epithelioid cell
granulomas, primarily involving the lungs and
the lymphatics
• Chronic disease with variable manifestations
and clinical course
• Diagnosis is established when compatible
clinico-radiological features are supported
by histological evidence of noncaseating
epithelioid granulomas
Sarcoidosis
• Triggered by persistent presentation of as-yet unidentified,
poorly degradable antigen(s) in genetically susceptible hosts
• Th1-type cellular immune response leading to noncaseating
epithelioid granulomas
Helpful diagnostic tools
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CD4/CD8 ratio > 3.5 in BAL
Angiotensin-converting enzyme (ACE) levels twice higher
than the upper normal limit
typical abnormal calcium metabolism
negative bacterial or fungal cultures may be helpful in
establishing the diagnosis
Spagnolo P, et al. Am J Med 2012; 125: 118-125
Histology of sarcoidosis
• Granuloma is the histologic hallmark of
sarcoidosis
Morphology:
well formed, compact, generally nonnecrotizing, typically surrounded by a rim of
lamellar hyaline collagen
Growth pattern
Granulomas typically coalesce along the
lymphatic routes in the pleura, interlobular
septa, and bronchovascular bundles
Cavazza A, et al. Int J Surg Pathol 2009; 17: 219-230
Courtesy: Dr. Cavazza (Reggio Emilia)
Sarcoidosis vs sarcoid-like reaction
Premise
• At histology, it may be very
challenging, if not impossible, to
differentiate sarcoidosis from
sarcoid-like reaction
• These latter may commonly occur
either adjacent to the primary
malignant site or to local drainage
nodes, possibly representing an
immunological hypersensitivity
reaction to tumor cells
Sarcoidosis & Cancer
• merely a
coincidence
• common
pathophysiologic
mechanism
• Incidence of lymphoproliferative disorders is
higher among sarcoidosis patients as
compared with the general population
• Precise mechanism of this association is
unclear: the chronic active type of
sarcoidosis appears to be responsible for an
increased risk of malignant transformation of
lymphoid cells
• Persistent active sarcoidosis, anergy, and
lymphopenia are usually associated with the
syndrome
• There exists a syndrome of sarcoidosis following
malignancy with/without chemotherapy (9 months
median interval)
Lymphoma-sarcoidosis syndrome
• Patients with different hematologic
malignancies (Hodgkin and non-Hodgkin
lymphoma but also T-cell lymphoma,
mycosis fungoides, chronic lymphocytic
leukemia, nonlymphocytic leukemia) may
subsequently develop sarcoidosis
• Sarcoidosis triggered by the
immunosuppressive treatment (?)
• Chronic inflammation is associated with an
increased risk for malignant lymphomas or
cancer in the affected tissue
• Incidence of cancer among 2,013 White and 3,755
Black male patients admitted to Veterans hospitals
in the United States during 1969–1996 with a
diagnosis of sarcoidosis, with that of 2,792,503
White and 662,204 Black non-sarcoidosis patients
admitted to the same hospitals
• Sarcoidosis patients
experience an
increased risk of some
neoplasms, in particular
colo-rectal and renal
cancer
• This study does
not support the
theory of an
association
between
sarcoidosis and
malignancy
• Selection bias and
misclassification
• Sarcoid reactions in
mediastinal lymph
nodes occurred in up
to 3% of lung cancer
cases
• Relationship between
a malignant tumor and
sarcoid reaction is a
host-versus-tumor
response, or a
reaction to metabolic
disintegration
substances released
from tumor cells
• Sarcoid-like reaction
was suspected in
1.1% of cancer
patients at FDG
PET/CT examination
• SUVmax of
confirmed hilar and
mediastinal sarcoidlike reaction was 7.3
(range 3.1e13.6)
• Important to avoid a
false-positive
interpretation of
metastatic disease
Sarcoidosis or sarcoid-like reaction ?
• Several solid tumors (e.g., breast, kidney, testis,
lung, melanoma, colon, liver) may show sarcoid-like
reactions associated with malignancy, adjacent to
the primary malignant site or in local drainage
nodes, or at distant sites
• The majority of the works describing sarcoidosis
with cancer report on the presence of noncaseating granulomas in patients who do not fulfill
the diagnostic criteria for systemic sarcoidosis
• The latter situation is the most challenging to
diagnose
Sarcoidosis or sarcoid-like reaction ?
Sarcoid-like granulomas in different diseases
Sjogren
Crohn disease
Common variable
immunodeficiency
Drug toxicity
Courtesy:(methotrexate)
Dr. Cavazza (Reggio Emilia)
Sclerosing cholangitis
Sarcoidosis &
colon cancer
metastasis
“sarcoidosic nodule with
numerous epithelioid
granulomas and giant cells
in the medium lobe”
Intrapulmonary reactive lymph node with sarcoid-like reaction
Sarcoidosis or sarcoid-like reaction ?
• Imaging studies alone (CT or 18FDG-PET)
failed to discriminate sarcoid-like reaction
from metastasis
• Pathologic confirmation is mandatory
• FNA cytology is a less invasive and highly
effective method in differentiating cancer
from sarcoidosis/sarcoid-like reaction
• A diagnosis of sarcoidosis is based on
clinical and radiological presentation,
evidence of non-caseating granulomas, and
evidence of no alternative diseases
Valeyre D, et al. Sarcoidosis. Lancet 2014; 383: 1155–67
Final remarks
-Sarcoidosis and cancer may co-exist
- The mechanisms underlying the association of these 2
diseases is poorly-elucidated
- A patient with sarcoidosis may develop a cancer, but
even a sarcoid-like reaction may commonly occur in a
patient with cancer and may lead to an erroneous
- Whether
sarcoidosis have an
diagnosispatients
of cancer with
progression
increased
for developing
malignancies
is still
- In casesrisk
of mediastinal
nodes, fine
needle aspiration
cytology can effectively differentiate cancer from sarcoiddebatable
like granulomas/sarcoidosis
- Unbiased
studies on large populations are needed
- Sarcoid-like reaction at histology does not mean
sarcoidosis (misdiagnosis !)