Appendageal tumours

Introduction

• The majority of appendageal tumours differentiate towards or arise from either the pilosebaceous apparatus (hair follicle, sebaceous gland and in some body sites the apocrine gland) or the eccrine sweat glands
• The pilosebaceous units are concentrated in the head and neck area with the pilar element predominant on the scalp and the sebaceous element on the face, chest and upper back. The apocrine sweat glands are mainly found in the axilla, breast and perineal area. The eccrine sweat glands are found on all body sites
• Classification of appendageal tumours is not always straightforward as the ductal portions of the eccrine and apocrine glands are identical and cannot be differentiated on morphological grounds unless the apocrine duct can be identified entering the hair follicle 
• Appendageal tumours are relatively rare, their clinical appearance is commonly non-specific, and the vast majority are not diagnosed until after excision
• Most appendageal tumours are benign, malignant tumours are rare
   

Clinical relevance

• Most appendageal tumours, especially if found in small numbers, are of no or limited significance - a comprehensive, but not complete, list of appendageal tumours is found below in the sections on clinical findings and images, lesions are listed alphabetically
• It is, however, worth giving additional mention to the most clinically relevant appendageal tumours and syndromes, which are as below

The most clinically relevant appendageal tumours

• Appendageal carcinomas
  • Sebaceous carcinoma
  • Paget's disease of the nipple and extra-mammary Paget's disease 
  • Eccrine gland carcinomas  - the most common of this group is the malignant eccrine poroma
  • Apocrine gland carcinomas
• Sebaceous adenoma / epithelioma - even a solitary lesion can be associated with the Muir-Torre syndrome (see below) 
• Multiple / large numbers of benign appendageal tumours
  • Such patients are more likely to have an associated syndrome eg multiple trichilemmomas as part of Cowden's syndrome, and multiple fibrofolliculomas and trichodiscomas as part of the Birt-Hogg-Dube syndrome (see below)
  • Some conditions with multiple tumours eg syringomas have no significant associations 
• Naevus sebaceous
  • Usually presents at birth or in young children as a slightly raised yellow to tan plaque on the scalp or face
  • Rarely can transform into BCC - refer to clinical findings for more information
• Syringocystadenoma papilliferum
  • Often occurs in association with the above, or occasionally presents separately as a pink plaque or linear arrangement of papules
  • Rarely can transform into BCC - refer to clinical findings for more information
     

Associated syndromes

• Birt-Hogg-Dube syndrome

  • Characterised by multiple fibrofolliculomas and trichodiscomas over the face, neck and upper trunk. Skin lesions tend to appear in the third and fourth decades. Large numbers of skin tags can be found
  • It is associated with renal tumours and carcinomas, the risk for renal carcinoma is estimated to be 16-30%. A history of spontaneous pneumothorax and / or lung cysts supports the diagnosis

• Brooke-Spiegler syndrome

  • An autosomal dominant disorder
  • Characterised by the development of trichoepitheliomas, spiradenomas and cylindromas in early adulthood. Tumours most commonly develop on the head and neck
  • Affected individuals are at an increased risk of developing tumours in tissues other than skin appendages, particularly benign or malignant tumours of the salivary glands

• Cowden syndrome (syn. multiple hamartoma syndrome)

  • An autosomal dominant condition with variable expression
  • Patients tend to present as young adults with increasing numbers of hair follicle tumours (in particular trichilemmomas), a cobblestone appearance of the oral epithelium, oral papillomas and multiple skin tags
  • It is associated with a very high incidence of breast, thyroid and gastrointestinal carcinomas

• Gardner syndrome

  • An autosomal dominant condition
  • Characterised by multiple epidermoid cysts especially on the face and scalp, fibrous tissue tumours, osteomas and polyposis of the colon. Other features include abnormalities of the skull / facial bones and dental problems
  • Colonic malignancy develops in over 40% of reported cases

• Muir-Torre syndrome

  • A rare autosomal dominant condition
  • It is diagnosed by a combination of any of, sebaceous adenomas (in 25-60% of cases), sebaceous epitheliomas, sebaceous carcinomas or multiple keratoacanthomas PLUS one of the following visceral carcinomas - predominantly colorectal but also gastric, small bowel, endometrial, ovarian, urinary tract and hepatobiliary

Management of patients with suspected syndromes

• Is often multidisciplinary
• All patients need referring to a genetics clinic for further investigations
• For more information on rare syndromes refer to Genetics Home Reference or follow the links for Genodermatoses  

While appendageal tumours can arise on any part of the body, the list below sets out the most commonly affected sites for each individual tumour. Following on from this list is more detailed information on each tumour. 

SCALP
Trichilemmal cyst
Naevus sebaceous (solitary, can also affect the face. Tan-coloured plaque)
Syringocystadenoma papilliferum (often arises within a naevus sebaceous)
Cylindroma (solitary or multiple, can also affect the face. Smooth, firm and rubbery, pink-red nodules)

PERI-ORBITAL
Apocrine hidrocystoma (predilection for the lower eyelid, particularly the medial canthus. Dome-shaped translucent papule, often pigmented)
Eccrine hidrocystoma (as opposed to the above they tend not to involve the eyelid margin but rather are distributed around the eyelid skin, and have a lighter colour) 
Syringoma (eyelids and cheeks. Multiple small, skin-coloured to yellow, rounded or flat-topped papules) 
Sebaceous carcinoma (eyelids, especially upper eyelid. Solid yellow-orange lesion, often with a translucent appearance)

CENTRAL FACE
Trichofolliculoma (a skin-coloured papule or small nodule with several hairs protruding together in a small tuft)
Trichoepithelioma (a solitary lesion looks like a BCC. Multiple lesions are small pearly papules)
Trichodiscoma (multiple, discrete flat-topped papules, 2-3 mm in diameter)
Trichilemmoma (solitary or multiple. Small, well-defined, smooth, asymptomatic papules or verrucoid growths)
Fibrofolliculoma (multiple small papules, centered around nose, anterior neck and chest. Lesions may be oval in shape but are not all uniform in size)

LIPS
Microcystic adnexal carcinoma (a subtle, elevated or depressed sclerotic papule or nodule) 

OTHER PREDOMINANTLY FACIAL LESIONS
Sebaceous gland hyperplasia (multiple 1-3 mm sized soft, white-yellow or skin coloured papules)
Sebaceous adenoma (a yellow-tinged, facial nodule under 1 cm in diameter)
Pilomatricoma (head and neck most common sites but can affect anywhere. A stony hard, deep-seated lesion, 3-30 mm in diameter)
Inverted follicular keratosis (solitary papule, which can become inflamed, pruritic and reach a considerable size)
Tumour of the follicular infundibulum (an irregular, often scaly, papule / nodule)
Mixed tumour of the skin (an asymptomatic, slow growing, intra-dermal or subcutaneous firm, white / yellow nodule)

TRUNK
Paget's disease of the nipple
Eruptive vellus cysts (multiple small, red or brown papules, mainly on the chest)
Spiradenoma (trunk and proximal limbs most common sites. Solitary, firm, dome-shaped nodule. Can be painful)

AXILLAE
Apocrine carcinoma (head and anogenital skin can also be affected. Presents as an expanding nodule, which can ulcerate)

EXTREMITIES 
Eccrine poroma (soles of the feet, palms less commonly. Solitary, soft, nodular, moist lesion with a sessile or broadly pedunculated base) 
Malignant eccrine poroma (lower limbs. The trunk and less commonly the head can also be affected. Lesions are ulcerated, red and dome-shaped nodules, with shiny surfaces)

ANOGENITAL SKIN
Extramammary Paget's disease (well-defined, pink-red patches) 
Hidradenoma papilliferum (the vulva more than perianal skin. A rounded, firm, slow growing nodule) 

SITE: NON-SPECIFIC 
Hidradenoma (an isolated red or bluish nodule)
Hidroacanthoma simplex (a verrucous plaque, usually with a hyperkeratotic brown surface)
 

A-Z of appendageal tumours 

• Apocrine carcinoma

  • ​A primary cutaneous apocrine carcinoma is a rare and highly aggressive cutaneous adenocarcinoma, metastatic spread occurs in upto 30% of cases
  • Age - more common in middle-aged women
  • Distribution - the axilla is the most common site, other affected sites include the head and anogenital skin 
  • Morphology - the lesion presents as an expanding nodule, which can ulcerate. As with many other appendageal tumours the diagnosis is not apparent until after histological analysis 

• Apocrine hidrocystoma

  • A relatively common, benign tumour of the apocrine secretory glands
  • Age - adults 
  • Distribution - the most common site is around the eye, with a predilection for the lower eyelid, particularly the medial canthus. Other body sites can be affected 
  • Morphology - usually a solitary, smooth, well-defined, dome-shaped translucent papule / nodule. Skin coloured to blue-black, pigmentation may affect all or part of the cyst. On palpation lesions are fluctuant and cystic

• Cylindroma

  • ​A tumour of unknown origin affecting women more than men
  • Solitary cylindromas occur sporadically and typically are not inherited. Multiple tumours are observed in an autosomal dominantly inherited manner 
  • Can be seen in conjunction with spiradenomas suggesting a similar derivation of both tumours
  • Age - usually early adult life but can be younger
  • Distribution - the scalp and less so the face
  • Morphology
    • Smooth, firm and rubbery, pink-red nodules. Can be pedunculated
    • When nodules enlarge and coalesce on the scalp they form the distinctive turban tumour feature
  • ​Associations - a combination of cylindromas, spiradenomas and trichoblastomas are found in the Brooke-Spiegler syndrome (refer to section on history)

• Eccrine hidrocystoma

  • A tumour composed of mature, deformed eccrine sweat units
  • Age - mainly middle-aged women
  • Distribution - ​cheeks and periorbital
  • Morphology - small and tense thin-walled cysts ranging from 1 to 6 mm in diameter. They are typically dome-shaped and have an amber, brown, or bluish tint. Eccrine hidrocystomas usually do not involve the eyelid margin but rather are distributed around the eyelid skin; this, along with a lighter colour differentiates it from the apocrine hidrocystoma 

• Eccrine poroma

  • ​A tumour arising from the eccrine duct epithelium 
  • Age - middle-aged onwards  
  • Distribution - the soles and sides of the feet are the most common sites, the palms can also be affected
  • Morphology - usually arise as a soft, non-tender, papular / nodular, moist lesion with a sessile or broadly pedunculated base, ranging in colour from tan to red / pink. Size can be up to 3 cm in diameter, but most are smaller
  • Lesions occasionally undergo malignant transformation into a malignant eccrine poroma (syn. porocarcinoma) - refer to the relevant section below for more information

• Eruptive vellus cyst

  • An occlusion and cystic dilatation of vellus hair follicles
  • Age - usually present in the second decade of life
  • Distribution - the chest
  • Morphology - usually multiple, small red or brown papules
  • If treatment is required topical retinoids may help. Surgical treatments such as curettage, or laser therapy are other options but scarring, especially on the chest can result

• Extramammary Paget's disease (EMPD)

  • Paget's disease and extramammary Paget's disease (EMPD) are uncommon intraepithelial adenocarcinomas composed of neoplastic cells showing glandular differentiation. Adenocarcinoma cells do not necessarily need to be part of a gland but may possess secretory properties (refer below for further information on Paget's)
  • The tumour cells of EMPD originate either from the intraepidermal cells of apocrine gland ducts or from pluripotent keratinocyte stem cells
  • Unlike mammary Paget's disease, where the proportion of cases in which an associated neoplasm can be demonstrated is high, most of cases of EMPD are not ie they are primary tumours. Approximately 25% of cases of EMPD are a secondary phenomena with the primary tumour arising in deeper appendageal structures of the dermis or from organs with a contiguous epithelial lining eg perianal EMPD is associated with adenocarcinoma of the gastrointestinal tract, and genital-groin EMPD is associated with genitourinary malignancy
  • EMPD is seen more frequently in women than in men, in women it has a predominantly vulvar distribution 
  • Age - arises in the fifth decade or after 
  • Clinical features:
    • The most common symptom is of a mild to moderate itch
    • Bleeding may occur secondary to scratching
    • Can affect perianal, and genital-groin sites 
    • The lesion has a well-defined and slightly elevated edge, which encloses a pink-red area of skin. The surface can have erosions, crusts and scale
    • Unlike eczema the lesion fails to clear up with topical steroid creams
  • Management
    • Wide local excision, or if available, margin-controlled surgical excision (Mohs micrographic surgery) is the standard treatment for EMPD. Recurrence is common (30-50%), so patients need regular follow up and further surgery may be needed  
    • Further investigation may be required to look for internal malignancy 

• Fibrofolliculoma

  • A rare tumour of the perifollicular connective tissue 
  • Age - usually appear in the third and fourth decades
  • Distribution - affect the upper trunk, neck, face (often centered around the nose) and sometimes the ears, the number and size of the fibrofolliculomas may increase with age, large numbers can be present
  • Morphology - slightly paler than the surrounding skin, small papules, which may be oval in shape but are not all uniform in size
  • Associations - one of the most common symptoms of the Birt-Hogg-Dube syndrome (refer to section on history)

• Hidradenoma

  • Can be apocrine or eccrine in origin
  • Age - mainly adults
  • Distribution - any body site
  • Morphology - an isolated red or bluish nodule

• Hidradenoma papilliferum

  • An apocrine tumour of the female anogenital skin
  • Can be either asymptomatic or ulcerate and bleed
  • Age - middle-aged women
  • Distribution - the vulva is much more commonly affected than the perianal skin. Rarely other body sites can be affected 
  • Morphology - a rounded, firm, slow growing nodule

• Hidroacanthoma simplex

  • A rare intraepidermal benign tumour, derived from the eccrine duct epithelium 
  • Distribution - has a predilection for the extremities, although the trunk can also be affected 
  • Morphology - a verrucous plaque, usually with a hyperkeratotic brown surface. It can mimic a seborrhoeic keratosis

• Inverted follicular keratosis

  • A hair follicle tumour
  • Age - middle-aged and older individuals 
  • Distribution - the head and the neck are the most common sites 
  • Morphology - most commonly presents as a solitary papule, which can become inflamed, pruritic and reach a considerable size. Can mimic malignant lesions, especially squamous cell carcinoma, both clinically and pathologically 

• Malignant eccrine poroma (syn. porocarcinoma)

  • The most common of the sweat gland carcinomas
  • Age - most cases arise in older patients. Women are affected more than men
  • Distribution - most commonly present on the lower limbs. The trunk and less commonly the head can also be affected 
  • Morphology - the most common presentation is that of an ulcerated, red, dome-shaped nodule with a shiny surface. They can also present as a wart-like plaque. Tumours tend to grow slowly and can become very large
  • 18% of lesions arise from a pre-existing benign eccrine poroma (refer above for more information) - malignant change should be considered in lesions that start to grow, become painful, ulcerate or bleed 
  • Lesions have metastatic potential so wide excision in Secondary Care and follow up are required 

• Microcystic adnexal carcinoma (syn. sclerosing/syringomatous sweat duct carcinoma, malignant syringoma)

  • A relatively rare, low-grade eccrine gland carcinoma
  • Lesions can be painful if not treated promptly as perineural spread is possible 
  • Age - any age although young to middle-aged patients are most frequently affected
  • Distribution - typically occurs on the head and neck, particularly the upper lip and other parts of the central face
  • Morphology - often a rather subtle, elevated or depressed sclerotic plaque or nodule 
  • Metastatic spread is rare but local recurrence is common and can be extensive with neurological involvement. Mohs surgery should be considered as a first line treatment

• Mixed tumour of the skin (syn. chondroid syringoma)

  • A rare tumour
  • Age - most commonly arise in middle-aged individuals
  • Distribution - 80% are located on the face, although any site can be affected
  • Morphology - the usual presentation is of an asymptomatic, slow growing, intradermal or subcutaneous firm, white / yellow nodule. Lesions can reach a large size

• Naevus sebaceous of Jadassohn (syn. sebaceous naevus, organoid naevus)

  • A naevus sebaceous is an organoid naevus comprised predominantly of sebaceous glands (an organoid naevus is characterised by hyperplasia of organoid epithelial structures such as the sebaceous glands, sweat glands and hair follicles)
  • They are seen in 0.3% of all neonates, with an equal incidence in males and females
  • Lesions are congenital and usually seen at birth, although they are occasionally first reported later in life
  • Distribution - the scalp, followed by the face are the most common sites 
  • Morphology
    • They present as slightly raised yellow to tan plaques
    • Smooth or velvety surface
    • If on the scalp the lesions are devoid of hair
    • They become papillomatous at puberty
    • A naevus sebaceous can occasionally transform into a basal cell carcinoma (BCC) - in the past it was believed that this happened in approximately 4% of cases, however, it is now believed that many of the lesions previously diagnosed as BCC where instead trichoblastoma's, which are benign. As a result there is a move away from excising all naevus sebaceous lesions and instead offering watch and wait if the patient chooses to do so
    • Associations - large lesions are occasionally associated with a wide range of developmental abnormalities and the epidermal naevus syndrome

• Paget’s disease of the nipple

  • Paget's disease and extramammary Paget's disease (EMPD) are uncommon intraepithelial adenocarcinomas composed of neoplastic cells showing glandular differentiation. Adenocarcinoma cells do not necessarily need to be part of a gland but may possess secretory properties (refer above for further information on EMPD)
  • The neoplastic cells in Paget's disease probably originate from the apocrine duct-derived epithelial cells of the breast, either as in situ adenocarcinoma of the breast or a more widespread infiltrating cancer, although this is sometimes difficult to detect on clinical examination or by mammogram
  • Paget's disease affects women and only rarely men
  • Age - it is rare before the fourth decade and most commonly arises in the fifth and sixth decades
  • Clinical features are as follows:
    • The condition is unilateral, rarely bilateral
    • Initial changes can be subtle with small, moist and intermittently crusted areas on the nipple
    • Over time surfaces changes persist and slowly evolve into a sharply marginated, crusty plaque with an irregular outline - areas affected include the nipple, areola and in later stages the skin of the breast
    • Occasionally there may be a blood stained discharge, nipple retraction or a palpable lump 
  • Patients with suspected Paget's disease should referred as a 2 Week Rule to a breast clinic

• Pilomatricoma (syn. pilomatrixoma)

  • A hamartoma of the hair matrix, and the most common of the hair follicle tumours 
  • Age - the majority of patients are under 20 when they present, although can arise at any age 
  • Distribution - mainly the head, neck and upper extremities
  • Palpation - a stony hard, deep-seated lesion, 3-30 mm in diameter, with normal overlying skin 
  • Occasionally lesions arise in older patients when they often grow more rapidly and may occur at atypical sites
  • Malignant change is rare and most commonly occurs in large lesions 
  • Provide a patient information leaflet

• Sebaceous adenoma and sebaceomas 

  • ​Benign tumours composed of incompletely differentiated sebaceous cells
  • Distribution - the face and scalp are the most common sites
  • Morphology - A yellow-tinged facial nodule, usually under 1 cm in diameter 
  • Associations - patients found to have one or more such lesions should be suspected as having the Muir-Torre syndrome (refer to section above on history)
• Sebaceous carcinoma
  • A malignant tumour composed of cells showing differentiation towards the sebaceous epithelium
  • Women are more commonly affected than men
  • Age - most lesions arise in middle-aged and older patients, the average age of presentation is approximately 70 years
  • Distribution - sebaceous carcinoma most commonly affects the upper eyelid, probably as a result of a higher number of meibomian glands in this location 
  • Morphology - sebaceous cell carcinoma is known for its ability to masquerade as other diseases, such as chalazion or blepharitis. The most common findings are that of a solid, yellow-orange lesion, often with a translucent appearance
  • Management - complete surgical excision is required as local recurrence rates range from 10% to 35%, metastases can occur 
  • Associations - as with other sebaceous gland tumours (except sebaceous gland hyperplasia ) patients should be suspected as having the Muir-Torre syndrome (refer to section above on history)

• Sebaceous gland hyperplasia

  • ​Multiple 1-3 mm sized soft, white-yellow or skin coloured papules on the face
  • This conditions has no associations and is discussed elsewhere on the website (refer to related chapters at the top of the page)

• Spiradenoma (syn. eccrine spiradenoma)

  • The histogenesis of spiradenomas remains in question, but many lesions demonstrate apocrine differentiation
  • Age - most commonly arises in people aged 15 to 35 years
  • Distribution - the front of the trunk and proximal limbs are the most common sites 
  • Morphology - usually presents as a solitary, 1 cm, firm, dome-shaped nodule. Some are painful and tender to touch. Their colour can vary but many have a bluish element 
  • Associations:
    • Spiradenomas can arise in cyclindromas, it has been suggested that the two may be part of the same spectrum
    • A combination of cylindromas, spiradenomas and trichoblastomas are found in the Brooke-Spiegler syndrome

• Syringocystadenoma papilliferum

  • Although classified as an organoid naevus the exact nature of this lesion remains controversial
  • Many cases arise in sebaceous naevi at or after puberty. They can occasionally present as an isolated finding, mainly on the scalp / face at birth or early infancy. On the scalp they appear as a pink plaque or linear arrangement of papules. On other parts of the body they present as a linear lesion following the lines of Blaschko
  • A rare solitary form presents as a nodule or cutaneous horn
  • As with the naevus sebaceous lesions can occasionally transform into BCC

• Syringoma (syn. syringocystadenoma, syringocystoma)

  • A benign eccrine gland tumour more commonly found in women 
  • Age - most commonly arises in adolescence
  • Distribution - the face, especially the cheeks and eyelids
  • Morphology - multiple small, 1 to 5 mm, skin-coloured to yellow, rounded or flat-topped papules

• Trichilemmal cyst

  • An external root-sheath tumour
  • Relatively common
  • Females more than males
  • Distribution - mainly seen on the scalp, rarely the extremities
  • Morphology - firm nodules

• Trichilemmoma

  • A proliferation of the external root sheath of the hair follicle
  • Age - affect young and middle-aged adults
  • Distribution - the central face 
  • Morphology - solitary or multiple. Small, well-defined, smooth, asymptomatic papules or verrucoid growths
  • Associations - if multiple can be part of the Cowden syndrome (refer above to the section on history) 

• Trichoblastoma

  • A tumour of the hair gem cell composed of follicular germinative cells
  • Trichoblastomas and trichoepitheliomas appear to be part of the same spectrum. The main difference between trichoblastomas and trichoepitheliomas is the depth at which they arise in the dermis - trichoblastomas are found in the deep dermis and subcutaneous tissue, whereas trichoepitheliomas are more superficial
  • Age - adults, most commonly arising in the fifth and sixth decades

  • Distribution - head and neck 

  • Morphology - a dermal or subcutaneous skin-coloured papule / nodule, usually less than 1 cm in diameter
  • Can occur within a naevus sebaceous

• Trichodiscoma

  • A hamartoma of the hair follicle mesenchyme
  • Distribution - mainly the central area of the face
  • Morphology - multiple, discrete, flat-topped papules 2-3 mm in diameter 
  • Associations - can be found along with fibrofolliculomas as part of the Birt-Hogg-Dube syndrome (refer to section on history). However if the patient has only trichodiscomas and no other symptoms of the Birt-Hogg-Dube syndrome, this may be a sign of another condition called familial multiple discoid fibromas

• Trichoepithelioma

  • A hamartoma of the hair germ cell with focal, primitive follicular differentiation
  • Age - mainly young adults
  • Clinically, mainly presents on the face as:
    • A solitary nodule resembling a BCC - lesions need excising for diagnostic purposes, however, histologically they also can be difficult to distinguish from BCC
    • Multiple, small, pearly papules on the central face, inherited as autosomal dominant
  • A desmopastic trichoepithelioma (syn. sclerosing epithelial hamartoma) can look even more like a BCC with a depressed centre and raised, rolled edges in many cases

• Trichofolliculoma

  • A hamartoma of the pilosebaceous follicle
  • Age - mainly young adults
  • Distribution - the face, with a predilection for the central face around the nose 
  • Morphology - a skin-coloured papule or small nodule with several hairs protruding together in a small tuft

• Tumour of the follicular infundibulum 

  • A hair follicle tumour
  • Distribution - usually found on facial skin
  • Morphology - solitary follicular infundibulum tumours have no distinctive clinical features and usually present as an irregular, often scaly, papule / nodule up to 1.5 cm in diameter. Occasionally can be multiple
  • Associations - occasionally with the Cowden syndrome 

• Patients with a suspected appendageal carcinoma, or an incidental finding on histology of an appendageal carcinoma, need to be referred as a 2-Week Rule to dermatology or plastic surgery (refer to local guidelines), except for Paget's disease when patients need referring to a breast clinic
• For lesions associated with the syndromes listed in the section on history, patients should be referred to an appropriate dermatology / genetics clinic (refer to local guidelines)
• Otherwise refer to the section on clinical findings for more information

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