|
|
Classification of small cell carcinoma:
(International Association for the Study
of Lung Cancer):
- Small cell
(Pure form)
- Mixed cell small
cell/large cell
-
Combined (small
cell and adenocarcinoma or squamous carcinoma)
Classification of small cell carcinoma:
(WHO)
- Oat
cell
- Intermediate
- Combined
Image of Small Cell Carcinoma
(intermediate cell type)
|
Small cell carcinoma is the most malignant of lung
cancers and usually presents as a central or hilar tumour.
Visit:
Lung Tumour-Online
It is strongly
associated with cigarette smoking.
Tumours showing a
mixture of small cell carcinoma and large cell carcinomas are more
aggressive than pure small cell carcinomas and are less sensitive to
irradiation and chemotherapy.
Small-cell carcinoma grows very rapidly, metastasizes early and initially at least is
sensitive to chemotherapy.
Long-term
disease-free survival is seen in only a minority of patients treated with
chemotherapy.
Despite treatment, the patient usually dies
with widely disseminated disease within 1-2 years.
Surgeons claim to be able to treat a minority successfully,
but these cases are highly selective and some may represent atypical carcinoids rather than small cell carcinoma.
Small cell carcinomas are
generally central tumours arising in elderly cigarette smokers but rare
cases present as a peripheral nodule and it is these that have the best
chances of successful surgical eradication.
The combined subgroup is characterized by the
presence of squamous cell carcinoma or adenocarcinoma in addition to small
cell carcinoma.
The differences between the oat cell and the intermediate cell
types are imprecise and lack clinical relevance, possibly because the
described differences are artifactual.
Classic oat cell carcinoma is most often observed in traumatized biopsies
or poorly preserved autopsy material, whereas in well-preserved surgical
material the intermediate cell type is seen almost exclusively.
Accordingly, it has been recommended by some workers that the terms oat
cell and intermediate cell be abandoned.
It has been reported that tumours showing a
mixture of small cell carcinoma and large cell carcinoma are even more
aggressive than pure small cell carcinomas, and are less sensitive to
irradiation and chemotherapy. This lead to a new subdivision of small cell carcinoma in which the distinction
between oat-cell and intermediate subtype is discarded, and a new mixed
small cell/large cell caterory is recognized .
Mixed small cell/large cell carcinoma is variously estimated as forming
from 4 to 19% of all small cell carcinomas.
Microscopic features:
Microscopically, small cell carcinoma
is characterized by small, round or oval (oat-like) cells with
little cytoplasm and hyperchromatic nuclei, resembling lymphocytes.
Image1
;
Image2 ;
Image3
The
cells are arranged in nests or clusters. The cells may also be arranged in
rosettes, pseudorosettes, tubules or ductules.
Rosettes of radially arranged tumour cells may be formed and genuine lumina may also be
present and sometimes contain a little mucin.
The edge of the tumour
is ill-defined and lacks a capsule.
Necrosis is
commonly seen.
Haematoxyphil, Fuelgen-positive nucleoprotein
derived degenerate tumour cells may be deposited in the walls of stromal
blood vessels (Azzopardi effect) but this feature is also found
on occasion in other cellular tumours, such as lymphoma, seminoma and even
other types of lung carcinoma.
Mitoses are
numerous and the nuclei of adjacent tumour cells
characteristically press on one another, a feature termed nuclear moulding
that is especially prominent in cytological specimens.
It is sensitive to chemotherapy and irradiation.
Some small
cell carcinomas show scattered tumour cells with hyperchromatic giant
nuclei, especially in tumors after radiotherapy or chemotherapy.
Classic oat cells have dense pyknotic nuclei and
very sparse cytoplasm.
Intermediate cells are a little larger , have a
discernable but still small amount of cytoplasm and a nucleus with a
finely divided chromatin pattern. Nucleoli are inconspicuous in paraffin
sections but may be quite striking in plastic sections.
In biopsy specimens, the tumour cells are
often crushed so that long strands and masses of haematoxyphil material
are seen.
This finding should prompt a careful search for
viable, non-traumatized tumour cells but by itself does not justify a
diagnosis of small cell lung carcinoma because other tumours, and even
inflammatory infiltrates, may show the same crush artifact.
A partial
change to non-small cell histology during the course of the disease is
encountered in about a fifth of patients. This is relevant to the nature
of the mixed small cell/large cell category mentioned above.
In bronchial biopsies, the tumour cells are often
seen beneath an intact surface epithelium that shows atypical squamous
metaplasia.
Superficial sampling limited to this surface change may lead
to erroneous histological classification and, hence, the wrong treatment.
It is essential that invasive tumour be examined.
There may
be infiltration of the overlying epithelium by small groups of tumour
cells, similar to that seen in Paget’s disease of the nipple.
Differential Diagnosis:
- Small cell carcinoma is liable to be mistaken for large cell carcinoma
if attention is concentrated on cell size and the presence of sufficient amounts of cytoplasm. These two tumours
are best separated on their nuclear characteristics. The finely divided,
evenly dispersed chromatin of a small cell carcinoma contrasts greatly
with the clumped chromatin and prominent nucleolus set in an otherwise
vesicular nucleus of a large cell carcinoma.
- Lymphocytes, either reactive or neoplastic may also
be mistaken for small cell carcinoma, especially if the tissue is at all
traumatized. The carcinoma cells are larger than reactive
lymphocytes and may be distinguished from lymphoma cells by immunocytochemistry, using antibodies against leucocytes (CD45) and
cytokeratin.
- Some squamous cell and adenocarcinomas are composed small
tumour cells but these lack the nuclear features of small cell carcinoma
and show no immunohistochemical or ultrastructural evidence of
neuroendocrine differentiation.
Wider sampling generally reveals their
true nature.
If adequate, non-traumatized tissue is provided, small cell
carcinomas are relatively easily distinguished from other histological
types. It may be difficult to diagnose some cases, particularly in small
biopsies.
|
Electron microscopy:
Electron microscopy shows the characteristic 50-200
nm dense-core cytoplasmic granules but they are far fewer than in a
carcinoid.
They have to be distinguished from bristle-coated vesicles,
small lysosomes and small exocrine granules.
Bristle-coated vesicles have
a fuzzy surrounding membrane whilst lysosomes and exocrine granules lack
the halo separating the central core from the outer membrane.
Exocrine
granules are also usually more pleomorphic.
Minority of small cell
carcinomas show undoubted ultrastuctural evidence of squamous or mucous cell
differentiation, alone or in combination with dense-core granules.
Note: A variety of non-small cell carcinomas are sometimes found to
contain dense-core granules on electron microscopy.
Immunohistochemistry:
Immunohistochemistry shows that in line with their
epithelial nature, a range of cytokeratins may be demonstrated in small
cell lung carcinoma, often with a perinuclear or dot-like paranuclear
distribution.
Immunohistochemistry has been widely used in attempts to
distinguish small cell and non-small cell lung carcinoma, but no
completely satisfactory markers of neuroendocrine differentiation is
available.
At present, chromogranin A and synaptophysin
probably represent the best combination to establish the diagnosis.
Chromogranin A is
a fairly specific protein component of endocrine granules but is usually
difficult to detect because small cell lung carcinomas are only sparsely
granulated.
In situ hybridization may be useful here for it
demonstrates high levels of chromogranin A mRNA in these tumours.
Gastrin
releasing peptide (GRP ; human bombesin) is an autocrine growth factor for
both normal and neoplastic neuroendocrine cells and can be readily
demonstrated in carcinoids, but in only a minority of small cell
carcinomas.
GRP mRNA can
be consistently demonstrated in small cell carcinomas.
Leu-7, a surface
antigen present in human natural killer cells and neuroendocrine cells,
has also been used to identify a neuroendocrine subtype but its
specificity is not very high.
In contrast to these neuroendocrine markers,
CD44 is reported to be expressed only by non-small cell carcinomas.
|
Visit:
Neuroendocrine Tumours of the Lung
;
Central Carcinoid Tumour
;
Peripheral Carcinoid Tumour
;
Atypical Carcinoid
;
Large Cell Neuroendocrine Tumour
;
Diffuse
idiopathic neuroendocrine cell hyperplasia (DIPNECH)
;
Pulmonary Tumorlet
.
|
Pathology of small cell carcinoma of the lung.Semin
Oncol. 2003 Feb;30 (1):3-8.
Small cell
carcinoma of the lung is one of the major subtypes of primary lung
cancer. It is a highly aggressive lethal neuroendocrine carcinoma. It
is closely related to other neuroendocrine carcinomas of the lung,
including carcinoid, atypical carcinoid, and large cell neuroendocrine
carcinoma. This article discusses the classification of small cell
carcinoma of the lung, identifies its cytologic and histologic
characteristics, and places it in context with the other
neuroendocrine carcinomas of the lung.
Typical and
atypical pulmonary carcinoid tumor overdiagnosed as small-cell
carcinoma on biopsy specimens: a major pitfall in the management of
lung cancer patients.
Am J Surg Pathol. 2005 Feb;29(2):179-87.
Seven patients
with typical or atypical pulmonary carcinoid tumors overdiagnosed as
small-cell carcinoma on bronchoscopic biopsies are described.
Bronchial biopsies from 9 consecutive small-cell lung carcinoma
patients were used as control group for histologic and
immunohistochemical studies (cytokeratins, chromogranin A,
synaptophysin, Ki-67 [MIB-1], and TTF-1). The carcinoid tumors
presented as either central or peripheral lesions composed of tumor
cells with granular, sometimes coarse chromatin pattern, high levels
of chromogranin A/synaptophysin immunoreactivity, and low (<20%) Ki-67
(MIB-1) labeling index. The tumor stroma contained thin-walled blood
vessels. Small-cell carcinomas always showed central tumor location,
finely dispersed nuclear chromatin, lower levels of chromogranin A/synaptophysin,
and high (>50%) Ki-67 (MIB-1) labeling index. The stroma contained
thick-walled blood vessels with glomeruloid configuration. Judging
from this study, overdiagnosis of carcinoid tumor as small-cell
carcinoma in small crushed bronchial biopsies remains a significant
potential problem in a worldwide sample of hospital settings. Careful
evaluation of hematoxylin and eosin sections remains the most
important tool for the differential diagnosis, with evaluation of
tumor cell proliferation by Ki-67 (MIB-1) labeling index emerging from
our review as the most useful ancillary technique for the distinction.
Small cell
lung carcinoma in the form of multiple lung nodules. Arch
Bronconeumol. 1997 Jan;33(1):52-4.
Small cell
carcinoma of the lung occasionally presents as a single pulmonary
nodule, but its expression in the form of multiple pulmonary nodules
has not been reported in the literature. We describe a single case of
small cell carcinoma of the lung presenting as multiple pulmonary
nodules that seems to have been cured by chemotherapy.
Peripheral
small-cell carcinoma of the lung resembling carcinoid tumor. A
clinical and pathologic study of 14 cases.Arch
Pathol Lab Med. 1985 Mar; 109(3):263-9.
We studied 14
small-cell, epithelial tumors of the lung with histologic features
intermediate between typical carcinoid tumor and undifferentiated
small-cell carcinoma. All of the tumors arose in the periphery of the
lung beyond a segmental bronchus and were excised. Histologically,
three of the tumors were low grade and 11 were high grade. The
low-grade tumors had an organoid pattern comprising more than half of
the area examined histologically, less than five mitoses per 10
high-power fields, individual cell necrosis, and nuclear pleomorphism
of less than half of the cells. The high-grade tumors had the opposite
characteristics. Distinction of these peripheral tumors from typical
carcinoid tumors and from undifferentiated small-cell carcinomas is
established after excision and cannot be made reliably on the findings
of a transbronchial or needle biopsy. Prognosis was worse than that
for typical carcinoid tumors but better than that for undifferentiated
small-cell carcinomas.
The unusual spectrum of neuroendocrine lung neoplasms. Ultrastruct
Pathol. 1989 Sep-Dec;13(5-6):515-60.
Neoplasms of
the lungs showing neuroendocrine differentiation are classified
histologically into the following groups: (1) carcinoid, (2) atypical
carcinoid (well-differentiated neuroendocrine carcinoma and malignant
carcinoid, (3) small cell neuroendocrine carcinoma (small cell
undifferentiated carcinoma and oat cell carcinoma), and (4) large cell
neuroendocrine carcinoma (atypical endocrine tumor of the lung and
intermediate neuroendocrine carcinoma). Nine examples of
neuroendocrine lung carcinomas are discussed that have unusual
histologic features that make it difficult to assign them to one of
the above groups, have unusual immunohistochemical features, have
unusual ultrastructural features, or exhibit a biologic behavior
different from what one would have predicted from their morphologic
appearance. The findings in these nine cases suggest that the present
classification of neuroendocrine lung neoplasms may be too precise and
that these neoplasms, like other nonneuroendocrine pulmonary tumors,
exhibit a wider morphologic and biologic spectrum than previously
appreciated.
|
|
