Transcript Clue cells - Abdel Hamid Derm Atlas

Named cells in dermatology
Part II
Infectious disorders
IJDVL : 2012 : 78 | Issue : 2 : 207
Named cells in dermatology
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Part I: General category
– Normal cutaneous anatomy: Langerhans cells, Glomus cells, Veil cells, Mast cells
– Bullous disorders: Tzanck cells
– Eczematous disorders: Tadpole cells
– Metabolic and storage disorders: Gargoyle cells, Gaucher's cell, Xanthoma cells
– Tumors: Basalioma cells, Basophilic and shadow cells, Doughnut cells,, Granular cells, Halo
cells, Hibernoma cells, Paget cells, Sezary cells, Signet ring cells, Spider web cells, Strap
cells, Reed Sternberg cells, Vulvar Clear Cells of Toker, Floret giant cells
– Histiocytic disorders: Touton giant cells
– Collagen vascular disorders: LE cells, Tart cells
– Drug induced: Podophyllin cells
– Keratinization disorders: Mantle cells.
– Disorders of the panniculus: Bean bag cells
– Disorders of photoimmunology: Sunburn cells
– Benign pigmented lesions: Balloon cells
Part II: Infectious disorders
– Bacterial: Clue cells, Downey cells, Greenblatt and Pund cells, Lepra cells, Mikulicz cells,
Langhan giant cells
– Protozoal: Wright cells
– Viral: Koilocytes, Warthin Finkeldey cells, Mitosoid cells
Clue cells
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Clue cells
are epithelial cells of the vagina that get their distinctive stippled appearance by being covered
with bacteria. The etymology behind the term "clue" cell derives from the original research article
from Gardner and Dukes describing the characteristic cells. The name was chosen for its brevity
in describing the sine qua non of bacterial vaginosis. American journal of obstetrics and gynecology 69 (5): 962–976.
They are a medical sign of bacterial vaginosis, particularly that caused by Gardnerella vaginalis, a
group of Gram-variable bacteria. This bacterial infection is characterized by a foul, fishy smelling,
thin gray vaginal discharge, and an increase in vaginal pH from around 4.5 to over 5.5.
Clue cells
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Clue cells are vaginal squamous epithelial cells coated with the anaerobic gramvariable coccobacilli Gardnerella vaginalis and other anaerobic bacteria causing
bacterial vaginosis. Clue cells were first described by Gardner and Dukes in 1955 and
were so named as these cells give an important "clue" to the diagnosis of bacterial
vaginosis. A clue cell can be detected on simple wet mount of vaginal secretions. To
be significant for bacterial vaginosis (BV), more than 20% of the epithelial cells on the
wet mount should be clue cells.
Pathogenesis
Clue cell phenomenon is attributed to the attachment of adherent strains[2] of G.
vaginalis in large numbers to exfoliated epithelial cells of the vagina in presence of an
elevated pH. The increase in vaginal pH occurs due to alteration in normal flora
characterized by a decrease in lactobacilli and increase in bacteria such as G.
vaginalis ,Mycoplasma hominis and anaerobes as Mobiluncus, Bacteroides and
Peptostreptococcus species. Lactobacilli help to maintain the acidic pH of healthy
vagina and inhibit the growth of anaerobic microorganisms through elaboration of
hydrogen peroxide. Factors causing the change in flora are poorly understood.
Postulates include the menstrual cycle, concomitant infections, sexual activity,
contraceptive methods and antibiotic use. An increase in the local pH favors the
growth of bacteria causing BV. The bacteria adhere to the surface of epithelial cells
leading to formation of clue cells. Lytic cellular changes are induced by the organisms
on clue cells by production of enzymes such as sialidases (neuraminidases) allowing
the bacteria to invade and destroy the cells
Diagrammatic representation of normal vaginal squamous epithelial cells
with lactobacilli. The cell margins are distinct and lack granularity
Diagrammatic representation of clue cells coated with
coccobacillary organisms with a granular appearance and stippled
border
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The clue cells can be demonstrated by microscopic examination of vaginal wet mount
preparation.. The normal vaginal squamous epithelial cells have distinct cell margins
and lack granularity . Clue cells are seen as squamous epithelial cells with large
number of coccobacillary organisms, densely attached in clusters to their surfaces
giving them a granular appearance. The cytoplasm appears fuzzy (like shading with
black pencil) and the edges of the squamous epithelial cells, which normally have a
sharply defined cell border, become indistinct or stippled . Polymorpho nuclear
leukocytes (PMNs) can also be demonstrated on the normal vaginal wet mount
preparation. The vaginal discharge of patients with BV is notable for its lack of PMNs,
typically 1 or less than 1 PMN per vaginal epithelial cell.
Clue cells
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Detection of clue cells is the most useful single procedure for the diagnosis of
bacterial vaginosis which presents with malodorous vaginal discharge and vulvar
irritation.. Other criteria for the diagnosis of BV include: milky, homogeneous,
adherent discharge; vaginal pH greater than 4.5; positive whiff test i.e., typical fishy
odor on addition of one or two drops of 10% KOH to vaginal discharge and "few or no
lactobacilli". The presence of three of the above five is considered diagnostic.
The presence of clue cells in vaginal discharge has also been used to predict
postoperative infections after abdominal hysterectomy. Women with positive clue cell
detection in air-dried vaginal smears have been found to be at increased risk of
postoperative vaginal cuff infections and wound infections.
Vaginal wet mount with NaCl preparation, showing a clue cell at bottom left, and two
normal epithelial cells
Micrograph of bacterial vaginosis — cells of the cervix covered with rod-shaped
bacteria,Gardnerella vaginalis (arrows)
Workup of suspected bacterial vaginosis, with a pH indicator to detect vaginal alkalinization (here
showing approximately pH 8), and a microscope slide to microscopically detect clue cells.
Downey cell
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Downey cell
A typical lymphocyte which is an enlarged dysmorphic
lymphocyte . They are large because of antigen stimulation . They are
characterized by an often irregular monocyte like nucleus that may stretch the
may length of the cell, with chromatin strands that parallel the length of the nucleus;
nucleoli and azurophilic granules may be present. They are seen in various nonneoplastic conditions, classically in infectious mononucleosis (<20% of circulating
WBCs are atypical), toxoplasmosis, CMV infection and viral hepatitis. However, they
can also be present as a result of drug reactions (such
as phenytoin), immunizations, radiation, hormonal causes (such
as stress and Addison's disease) as well as some auto-immune disorders (such
as rheumatoid arthritis).
Some pathogen-related causes include:
Epstein-Barr virus
Cytomegalovirus
Toxoplasma gondi
Treponema pallidum (Syphilis)
Streptococcus agalactiae (Group B Streptococci),
Hepatitis C
Hantavirus
This distinctive cell is known as a "Downey cell", after Hal Downey, who contributed
to the characterization of it in 1923.
Downey cell surrounded by red blood cells
Downey cell
Robert B. Greenblatt (1906-1987)
Greenblatt made significant contributions to medicine including: the description of the
pathognomic cell in granuloma inguinale (with E.R. Pund); the first demonstration of oral
mycin drugs in the treatment of granuloma inguinale
Granuloma inguinale
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Beefy-red penile ulcers.
Section showing Pund cell with Donovan bodies (Giemsa stain)
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Micro description
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Massive plasma cell infiltrate without lymphocytes in granulation tissue
Diffuse infiltration by neutrophils forming microabscesses
Large mononuclear cells (also called Pund cells) with Donovan bodies (large
intracytoplasmic encapsulated bipolar bodies
Donovan bodies of granuloma inguinale
Granuloma inguinale
Lepra cells
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lepra cells
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distinctive, large, mononuclear phagocytes (macrophages) with a foam like
cytoplasm, and also poorly staining saclike structures resulting from degeneration of
such cells, observed characteristically in leprous inflammatory reactions; indistinct
staining results from numerous, fairly closely packed leprosy bacilli, which are acid
fast and resistant to staining by ordinary methods.
Lepra cells
Lepra cells
Lepra cells
Mikulicz cell
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MIKULICZ CELL
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a round or oval macrophage with a small nucleus that is found in the nodules of
rhinoscleroma and contains the causative bacterium (Klebsiella rhinoscleromatis) The
Mikulicz cell was identified morphologically as a macrophage, not a plasma cell.
Acutely inflamed areas of rhinoscleroma presented abundant bacteria with a slime
layer. The microorganism was infrequent and the mucopolysaccharide was scanty in
rhinoscleromal tissue, where plasma cells predominated, and in cicatricial fibrous
tissue. In the granulomatous stage of rhinoscleroma, the mucopolysaccharide was
found within the Mikulicz cells. The vacuoles observed in the Mikulicz cells were
considered to be phagosomes containing, principally, bacterial mucopolysaccharide
and few bacteria and, to a lesser extent, swollen mitochondria.
The slime layer of Klebsiella rhinoscleromatis plays an important role in the
pathogenesis of the disease. It is postulated that this material is a non digestible
mucopolysaccharide that resides in the phagosomes of macrophages, increases the
osmotic pressure and forms multiple hydropic vacuoles that rupture not only the
phagosomes but also the cells, resulting in the liberation of the mucopolysaccharide.
This would initiate a cycle that would prolong the disease in the absence of the
bacteria.
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In 1876, Mikulicz contributed to the microscopic histology. In 1882, Anton Von
Frisch (1849–1917) discovered the gram-negative bacillus which causes the
disease.
Micrograph showing abundant subepithelial histiocytes in a case of
rhinoscleroma. H&E stain
Mikulicz cell
Mikulicz cell
Langhans giant cells
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Langhans giant cells
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are large cells found in granulomatous conditions.
They are formed by the fusion of epithelioid cells (macrophages), and
contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery.
Although traditionally their presence was associated with tuberculosis, they are not
specific for tuberculosis or even for mycobacterial disease. In fact, they are found in
nearly every form of granulomatous disease, regardless of etiology. Langhans giant
cells are named after Theodor Langhans (1839–1915), a German pathologist.
They should not be confused with Langerhans cells, which are mononuclear
epidermal dendritic cells derived (like Langhans cells) from monocytes and named
after Paul Langerhans. (The Islets of Langerhans are also named after Paul
Langerhans.)
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Langhans giant cells
Koilocyte
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A Koilocyte is a squamous epithelial cell that has undergone a number of
structural changes, which occur as a result of infection of the cell by human
papillomavirus.
Koilocytosis or koilocytic atypia or koilocytotic atypia are terms used
in histology and cytology to describe the presence of koilocytes in a
specimen.
Koilocytes may have the following cellular changes:
Nuclear enlargement (two to three times normal size)
Irregularity of the nuclear membrane contour
A darker than normal staining pattern in the nucleus, known
as Hyperchromasia
A clear area around the nucleus, known as a perinuclear halo.
Collectively, these types of changes are called a cytopathic effect; various
types of cytopathic effect can be seen in many different cell types infected
by many different types of virus
These changes occur in the presence of human papillomavirus and
occasionally can lead to cervical intraepithelial neoplasia, and if left
untreated some may eventually progress to malignant cancer.
Koilocyte
Thin Prep pap smear with group of normal cervical cells on left and HPVinfected cells showing features typical of koilocytes: enlarged (x2 or x3) nuclei
and hyperchromasia
Dysplastic kilocytes from Pap smear can be easier to examine from sample
collected in transport media solution rather than on air-dried slide, because
there is less mucus and debris as well as thinner and more uniform distribution
of cells
Pap smear prepared on typical air-dried slide can contain
such artifacts as mucus and debris.
AUTOcyte system stores 120 of most significant cellular images from Pap
smear sample and displays them on 2 screens of 60 images each for
cytotechnologist to examine
Warthin–Finkeldey cell
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A Warthin–Finkeldey cell
is a type of giant multinucleate cell found in hyperplastic lymph nodes early
in the course of measles and also in HIV-infected individuals, as well as
in Kimura disease, and more rarely in a number of neoplastic
(e.g. lymphoma) and non-neoplastic lymph node disorders. Their origin is
uncertain, but they have previously been shown to stain with markers
similar to those of follicular dendritic cells, including CD21. Under the light
microscope, these cells consist of a large, grape-like cluster of nuclei.
Aldred Scott Warthin(1866 – 1931)
Warthin finkeldy cells
Warthin finkeldy cells
in measle lymphadenitis
Warthin finkeldy cells
in the germinal center
Warthin finkeldy cells in a lung
Focal Epithelial Hyperplasia
Mitosoid cells
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Epithelial hyperplasia in this disease presents microscopically as an abrupt
and sometimes considerable focal acanthosis of the oral epithelium. The
thickened mucosa extends upward, not down into underlying connective
tissues, hence, the lesional rete ridges are at the same depth as the adjacent
normal rete ridges. The ridges themselves are widened, often confluent and
sometimes club-shaped; they are not long and thin as in psoriasis and other
diseases. Some superficial keratinocytes show a koilocytic change similar to
that seen in other HPV infections, while occasional others demonstrate a
collapsed nucleus which resembles a mitotic figure (mitosoid cell). These
presumably result from viral alteration of the cells. Virus-like particles have
been noted ultrastructurally within both cytoplasm and nuclei of cells within
the spinous layer, and this layer is positive for HPV antigen with in
situ hybridization.
The lesion is usually easily differentiated from squamous papilloma, verruca
vulgaris and condyloma by its lack of pronounced surface projections; the
presence of mitosoid cells, and the lack of connective tissue cores in the
surface projections, when present. The sessile nature of focal epithelial
hyperplasia also serves to separate it from the former two lesions, although
this is not a guaranteed distinction.
Mitosoid cells
Mitosoid cells
Focal Epithelial Hyperplasia
Mitosoid cells