Sabtu, 03 Mei 2014

Verrucal-Papillary Lesions

Condyloma Acuminatum
• A sexually transmitted disease
• Associated with human papillomavirus (HPV) types 6, 11, 16, and 18 most often
• Can result in autoinoculation of other sites via trauma
• Lesions located at the site of contact/traumatic event
Clinical Presentation
• Usually on nonkeratinized tissues in immunocompetent patients (soft palate, lingual frenum)
• Pink to whitish pink, exophytic papillary growths with pedunculated outline
• May be solitary or multiple and variably sized, up to 2 to 3 cm
• Can present as papillomatosis of upper respiratory tract
• Location and appearance
• Demonstration of koilocytotic cellular changes on biopsy
• In situ hybridization or polymerase chain reaction reveals specific HPV subtype
• Electron microscopy demonstrates intranuclear virions
Differential Diagnosis
• Focal epithelial hyperplasia
• Multiple intraoral verruca vulgaris
• Squamous papilloma
• Conservative removal
• Conventional surgery
• Laser ablation
• Topical podophyllin
• Recurrences common
• Contagiousness and autoinoculation are considerations.
Condyloma Acuminatum

Focal Epithelial Hyperplasia
• A viral infection (HPV 13 or 32), usually found in childhood
• Familial/ethnic clustering often noted, probably secondary through horizontal viral transmission
• Often occurs in native Americans
Clinical Presentation
• Numerous, slightly raised whitish pink asymptomatic papules and irregular plaques that may become confluent
• Size of lesions ranges from a few millimeters to coalescent papules several centimeters in dimension
Microscopic Findings
• Well-defined acanthotic features
• Broadened, anastomosing epithelial ridges with occasional superficial koilocytotic changes
• Multiple, characteristic lesions
• Biopsy findings
• In situ deoxyribonucleic acid hybridization to demonstrate HPV subtype
• Ultrastructural localization of intranuclear virions
Differential Diagnosis
• Condyloma acuminatum
• Multiple verruca vulgaris
• None; lesions usually regress spontaneously
• Excision if esthetic needs demand
• Intralesional interferon therapy
• Excellent
• No reported malignant transformation

Focal Epithelial Hyperplasia

• Unknown, may be related to several factors, as follows:
• Viral—HPV subtypes 11, 13, 24, 33, 57
• Altered expression of cell cycle proteins including cyclin E, p53, PCNA
• Keratinocyte dedifferentiation reflected in deficient desmoglein production
• Immunosuppression
• Sun damage
• May represent a highly differentiated form of squamous cell carcinoma
• May indicate underlying alimentary neoplasia (Muir-Torre syndrome)
Clinical Presentation
• Usually solitary on sun-exposed areas, including lip
• Initially erythematous papule
• Rapid growth over 4 to 8 weeks
• Nodular, hemispheric, firm nodule
• Central keratin core
• Occasionally regresses spontaneously
• Extremely rare intraorally
• Clinical evaluation, follow-up
• Histopathology shows keratin plus normal, peripheral epidermis and mature, premature keratinization; no invasion below adnexa; marked pseudoepitheliomatous hyperplasia
Differential Diagnosis
• Squamous cell carcinoma
• Molluscum contagiosum
• Warty dyskeratoma
• Verruca vulgaris
• Pilomatricoma
• Condyloma acuminatum
• Squamous papilloma
• Observation and careful follow-up
• Local excision
• Cryotherapy
• Intralesional chemotherapy (methotrexate, 5-fluorouracil, or
• Excellent

• A benign proliferation of lymphatic vasculature
• Usually congenital in nature
Clinical Presentation
• Superficial or deep in location
• Typically waxes and wanes in size
• Most commonly involves the tongue followed by lips, buccal mucosa, palate
• Facial asymmetry may be a presenting sign.
• Superficial mucosal lymphangiomas resemble caviar or frog’s eggs.
• Deeper lesions present as painless fluctuant masses such as macroglossia.
• Often combined with blood vessels
• Rare variant may occur bilaterally on mandibular alveolar ridge of neonates
• Biopsy
• Lymphangiography
Differential Diagnosis
• Neurofibroma (deep)
• Hemihypertrophy syndromes
• Excision
• If large lesions are stable, observation
• Sclerotherapy
• Variable, depending upon depth and extent of lesion
• Cavernous variant has guarded prognosis

Papillary Hyperplasia (Palatal Papillomatosis)
• Generally attributed to ill-fitting maxillary denture
• Often associated with 24 h/d denture wearing
Candida albicans overgrowth common
• May be noted in habitual mouth breathers (nondenture wearers)
Clinical Presentation
• Erythematous palatal vault beneath denture
• Nodular papillary excrescences
• Generally asymptomatic
• Clinical appearance
• Biopsy results show fibrous and epithelial papillary hyperplasia; may note pseudoepitheliomatous hyperplasia
Differential Diagnosis
• Contact stomatitis
• Chronic candidiasis
• Denture stomatitis
• Establishment of good oral hygiene
• Possible antifungal therapy
• Surgical removal of affected mucosa, if excessive tissue hyperplasia
• Relining/remaking of denture
• Excellent
Papillary Hyperplasia (Palatal Papillomatosis)

Pyostomatitis Vegetans
• A pustular eruption usually associated with inflammatory bowel disease and skin disease
• Liver dysfunction (sclerosing cholangitis) may be associated in some cases.
Clinical Presentation
• Mucosal pustules, erythema, edema
• Erosions and ulcers may form with serpiginous outlines (“snail tracks”).
• Folds of nodular to hyperplastic tissue (“cobblestoning”)
Microscopic Findings
• Neutrophilic and eosinophilic infiltrate into epithelium producing microabscesses
• Infiltration between epithelial clefts
• Epithelial hyperplasia
• Correlation with underlying gastrointestinal disease, such as the following:
• Ulcerative colitis
• Crohn’s disease
• Sclerosing cholangitis
• Malabsorption syndrome
Differential Diagnosis
• Oral Crohn’s disease
• Pseudomembranous (acute) candidiasis
• Melkersson-Rosenthal syndrome
• Orofacial granulomatosis
• Acanthosis nigricans
• Successful management of underlying gastrointestinal disease
• Local anti-inflammatory agents
• Dapsone or sulfapyridine systemically
• Correlates with that of systemic disease
Pyostomatitis Vegetans

Squamous Papilloma
• A benign epithelial proliferation
• HPV is found in most cases; several subtypes have been identified, especially HPV 6 and 11.
Clinical Presentation
• Exophytic, papillary mass, measuring less than 1 cm
• Usually pedunculated and soft in texture
• White
• Usually solitary; may be multiple
• Favors soft palate; uvula, tongue, gingiva, buccal mucosa may also be involved
Microscopic Findings
• Epithelial hyperplasia with fibrovascular cores
• Papillary projections may be sharp to blunt.
• Epithelium may be dysplastic in some lesions from human immunodeficiency virus–positive patients.
• Clinical appearance
• Biopsy features
Differential Diagnosis
• Condyloma acuminatum
• Verruca vulgaris
• Focal epithelial hyperplasia
• Verrucous carcinoma
• Surgical excision
• Low recurrence rate
Squamous Papilloma

Verruca Vulgaris (Oral Warts)
• Infection of mucosal epithelium by members of the human papillomavirus group—usually HPV 2, 4, 6, or 11
Clinical Presentation
• Papular to nodular and exophytic appearance
• Surface texture is cauliflower-like or verruciform in nature
• Perioral skin lesions may be brownish.
• Oral mucosal lesions are usually white to pink.
• May be pedunculated or broad based
• Intraoral sites of predilection include the lips, palate, and attached gingiva.
• Multiple oral lesions may be evident in immunocompromised patients.
Microscopic Findings
• Surface hyperkeratosis
• Granulosis
• Koilocytosis
• Acquired immunodeficiency syndrome–associated oral warts may appear dysplastic microscopically.
• Clinical appearance
• Microscopic findings
• Immunohistochemical demonstration of HPV common antigen
Differential Diagnosis
• Focal epithelial hyperplasia
• Keratoacanthoma
• Papillary squamous carcinoma
• Squamous papilloma
• Condyloma acuminatum
• Excision
• Laser surgery
• Cryosurgery
• Electrosurgery
• Excellent in immunocompetent host
• Recurrence not uncommon
Verruca Vulgaris (Oral Warts)

Verrucous Carcinoma
• A well-differentiated, exophytic and endophytic squamous cell carcinoma often associated with tobacco use, especially smokeless tobacco
• A primary or ancillary role for HPV is suspected.
• May be preceded by keratotic patch (see “Verrucous
Hyperplasia” on page 158)
Clinical Presentation
• One-half of cases involve the buccal mucosa.
• Attached gingiva is involved in one-third of cases.
• Early, superficial lesions often are interpreted as verrucous hyperplasia; lesions become exophytic, irregular, and indurated.
• Advancing lesions push into adjacent tissues.
• Late lesions invade the periosteum and destroy bone.
• Metastases are rare.
Microscopic Findings
• Well-differentiated, blunt masses of epithelium extending into submucosa
• Intense lymphocytic infiltrate adjacent to invasive front
• Microscopic findings
• Full-thickness specimen is necessary to establish diagnosis
Differential Diagnosis
• Verrucous hyperplasia
• Papillary squamous cell carcinoma
• Proliferative verrucous leukoplakia
• Wide excision
• Radiation therapy may be effective.
• Dedifferentiation may occur spontaneously or after radiation therapy.
• Excellent
• Local recurrence is a distinct possibility.
Verrucous carcinoma

Verucous carcinoma

Verrucous Hyperplasia
• Unknown; tobacco (smokeless) associated most commonly
• Role of HPV is unclear.
• A possible precursor to verrucous carcinoma
Clinical Presentation
• Exophytic, papillary, keratotic fronds of epithelium
• May be part of the proliferative verrucous leukoplakia spectrum
Microscopic Findings
• Papillary to verruciform surface projections
• Keratin varies in thickness
• Broad, bosselated epithelial ridges
• Well-differentiated cellular features
• Some similarity to early verrucous carcinoma
• Microscopic features
Differential Diagnosis
• Verrucous carcinoma
• Papillary squamous cell carcinoma
• Proliferative verrucous leukoplakia
• Excision or ablation (eg, laser, electrocautery)
• Continued observation
• Good with complete excision
• Recurrence is common.
Verrucous Hyperplasia

Rabu, 05 Maret 2014

Chronic inflammation

What is Chronic Inflammation:
Inflmmation of prolonged duration in which inflmmation, tissuue injury and attempts at repair coexist, in varying combinations.

  1. Chronic Suppurative on acute: 
  2. Chronic granulomatus: (Initiates without an acute phase)
Suppurative in type:
  • Inadequate or delayed drain leads to thick fibrous wall    formation.                                         
  • The residual bacteria get reactivated
  • Pus formation.   
  • Presence of foreign material or indigestible dead tissue.
Eg: Osteomyelitis, damaged Collagen

Chronic inflammation
Follow acute inflammation
Persistence of the stimulus
Disturbance to the healing process
ŸRepeated bouts of acute inflammation and healing in between.
Low grade persistent infection.    

  • Microorganisms where body can mount limited immune reactions
  • Impaired Sequelae of an acute inflammation
  • Foreign bodies
  • body defense
  • Immune reactions

Chronic inflammation without an acute phase
Infection: TB, Leprosy, Syphilis
Immunological: Rheumatoid arthritis Ulcerative colitis Crohn’s disease
Poor blood supply (leg ulcer)

Chronic inflammatory lesions
May vary histologically according to causative agent
However there is a set of morphological features in common.  

  • Infiltration by mononuclear cells
  • Macrophages
  • lymphocytes
  • plasma cells
  • Proliferation of blood vessels/fibrosis (angiogenesis)
  • Fibrosis
  • Tissue destruction (induce by inflammatory cells)  
Mononuclear phagocytic system
Blood monocyte:
Macrophages (at extra vascular tissue) 
Tissue macrophages (Scattered in connective tissue or concentrated in organs)
Eg: Kupffer cells in Liver                                                                                                   
Sinus histiocytes in lymph nodes
Alveolar macrophages in lung
Osteoclasts in bones
Microglia (CNS)

Morphological transformation (macrophages and giant cells)
Secretion of biologically active products

Cells types present
  • Macrophages            Ÿ 
  • Eosenophils
  • Mast cells                 
  • ŸLymphocytes

Existence of CI, AI and repair
  • Macrophages persist at the site (Due to the influence of chemical mediators)
  • Destruction of invading microorganisms /normal tissues
  • Secretion of chemical mediators by macrophages
  • Functions of them,
  • Proliferation of fibroblasts, Laying down of collagen
  • Angiogenesis, Activation of lympho macrophages
  • ŸDead and dieing leukocytes/necrotic tissues helps in developing acute inflammation  
Granulomas /Granulomatus infection
  • Chronic inflammatory lesion in the form of mass.
  • Collection of macrophages or modified macrophages (epitheliod / giant cells)
  • Granulomas /Granulomatus infection
  • A granuloma is a focal area of granulomatus inflammation.
  • Consist of macrophage aggregation
  • Epithelial cell transformation
  • Collar of lymphocytes
  • Appearance giant cells and of fibrosis can see with the time 
  • TB
  • Sarcoidosis
  • Cat scratch disease
  • Leprosy
  • Syphilis
  • Mycotic infections
Two types of granulomas: Base on pathogenesis
Foreign body type:
Form around foreign bodies

Immune type: When the foreign practical are capable of induce cell mediate immune responses
(but not always granulomas will develop)

Granulomas is a result of chronic inflammatory reaction containing a collection of cells of monocytic series arrange in a compact mass.

Epithelioid cells
Giant cells: Langhans giant cells
Foreign body type giant cells  

Accumulation of macrophages
Under the influence of chemotaxis
C5a, fibrinopeptides, cationic proteins
Lymphokines :
PDGF, TGF(beta)
products of collagen brake down

By mitotic division 
Immobilization and prolong survival  (if the irritants are low virulent )

Chronic disease common worldwide.
Causes a characteristic granulomatous inflammation
Inability of the neutrophils to kill the micro organisms due to lipoprotein coating.

Mycobacterium tuberculosis.
Hominis (lungs)                                                
Bovis (Tonsils, Intestine) 

  • Droplet from patients (weeks or months)
  • Conjunctiva
  • Punctures
  • However need sustain contact than casual contact.

Tissue damage 
MT has no Endotoxins
Histiolitic enzymes

Development of immune response against outer coat of the organism.

Tuberculin test
2 to 4 weeks after infection : + Tuberculin test
PPD (purified protein derivative)
(Culture in which TB is grown)
Induration More that within 48 hours.
Positivity indicates infection but not the disease.

Primary Tuberculosis
Occurs in individuals who have never previously been infected with M. tuberculosis (childhood infection if TB is common, adult life if uncommon)

Usually caused by inhalation of the organisms or rarely by ingestion of the organism.

Primary infection
Lungs             Hilum
Tonsils           neck nodes
Intestine         mesentery

Primary Tuberculosis
In respiratory system, inhalation of the organisms cause a subpleural lesion usually in the lower part of the upper lobe or upper part of the lower lobe. This is called Ghon focus.

Location is in these sites is because bacterium is a strict aerobe and prefers these well oxygenated regions

Ghon’s focus
When the tissue is invaded by the mycobacteria there is no hypersensitivity reaction. Instead there is acute, non specific inflammatory response with predominant neutrophils.

This is followed by macrophages which ingest the bacilli and present Ags to to T lymphocytes leading to proliferation of a clone of T cells .

The emergence of specific hypersensitivity lead to release of lymphokines,that attract more macrophages.

These accumulate to form the characteristic granuloma.

Ghon focus
Usually single
1 to 2 cm
Location –Beneath pleura- mid zone of the lung 

Microscopic appearance

Primary complex
Tubercle bacilli, either free or contained in macrophages, may drain to the  regional lymph nodes and set up granulomatous inflammation, causing massive lymph node enlargement.

The combination of the Ghon focus, draining lymphatics and the regional lymph nodes is called the primary complex.

Calcification of the lymph nodes
Sequelae of primary complex
Healing  with small fibrous scar replacing caseous necrosis. Lesion will be walled off.
Reactivation of infection later when host defences become lowered.
plural effusion
Enlarged caseous nodes can obstruct bronchi, leading to collapse, retention of secretion and inflammatory consolidation

Caseous node erodes into a bronchi  with satellite lesions in lungs (TB bronchopneumonia).

Eroding into a pulmonary vein causing generalised milliary TB.

Erosion into pulmonary artery leads to miliary TB of lungs

TB bronchopneumonia
Opening of the caseous node to a bronchus.
Air bone infection
TB bronchopneumonia
(Multiple pneumonic patches arrangeed in and around terminal bronchi)
The lesions spread rapidly and accumulate macrophages and lymphocytes followed by necrosis 

Necrotic patches get enlarged and discharged which will lead to dissemination and cavitations. (no fibrous walls)
TB bronchopneumonia can happen after both 1ry and 2ry TB.  

Rapidly spreading tuberculous bronchopneumonia: debilitated by intercurrent disease, diabetes, malnutrition etc.
Acute miliary tuberculosis of the lungs due to blood stream spread to lungs. Grey tubercles visible to naked eye 3mm in diameter. More numerous and larger in upper lobes than lower lobes. Microscopically these are ill formed and often giant cells are absent. Usually these lesions do not cavitate

Effects on the other organs of the body
Miliary tuberculosis due to systemic spread to kineys, spleen, brain, liver etc.
Tuberculous ulcers in the intestine  due swallowed sputum.
Tuberculosis of larynx due to direct spread from sputum.
Secondary amyloidosis.

Miliary TB
Common with 1ry TB
Due to involvement of veins
Multiple scatted tubercles
Not well developed/uniform in size
1-2 mm
Some times without giant cells (necrosis)

Secondary  Tuberculosis (Post primary)
Infection may me exogenous or endogenous
After active primary infection
Reactivation asymptomatic primary lesions:
Severe illness,
Intercurrent lung infection,
Systemic immunosuppression
Exogenous: caused by inhaled organisms

During primary tuberculosis or during BCG immunisation, the patient develops cell mediated immunity to antigens of tubercle bacillus.
This is demonstrated by skin test (Mantoux) test
Immunity is associated with increased resistance to subsequent infection.

Re infected lesions:
Apex of the lungs
Endogenous infections (swallowing sputum) 
Metastatic lesions are similar to re-infected
Large in size (spread locally) no lymph node involvement

Cavity formation
Caseous material discharge gradually leaving a small cavity.
Cavities can become very large with overgrowth of fibrous tissue.
Cavity walls are irregular with raised bands representing obliterated blood vessels.
The surface is lined by caseous material or by pus and debris mixed with blood.
If the disease is inactive the wall becomes very smooth

In early cases the lesions are often in the apices of the lungs
In advanced cases there may be more than one cavitatory lesion.
All the lesions are distributed in the upper part of the lungs
Caseation may involve the wall of a bronchus leading to obstruction of the lumen.

Sequelae of tuberculous cavities
Local effects
Due to fibrosis lung tissue shrinks causing bronchiectasis (upper lobe bronchiectasis)
Blood vessels  can become weaken and rupture leading to haemoptysis
Aneurysm formation- called Rasmoussen’s aneurism leading to fatal haemorhage.
Fungal infections can be localized in these cavities.

Seen in non immune people.
Usually childhood cases
Subpleural mid zone

Lymph nodes are always involved
Seen in immune people

Often adults
Lung apices

Lymph nodes are not always involvecd