Dermpath Meeting Melbourne August 2008 Geoffrey Gottlieb spoke first on topographical dermatopathology. He talked initially of reactive processes that were site specific particularly lesions with pale nuclei looking like keratoacanthomas that may be seen in skin tags especially taken off the eyelid and the neck. They have a cloverleaf type of atypia. He then looked at neoplastic processes and said that if you see features of a BCC with some surrounding areas of keloidal collagen that the lesion is usually situated on the ear. If the BCC is deep enough in the ear then it can form this keloidal collagen. Also nodular BCC but with an infiltrated base that can be a lot more extensive than it looks is usually seen on the upper back but there is no stromal response to the BCC. Remember the shave biopsies may not pick this particular lesion up. It is one of those lesions that you initially think is a papular BCC and you excise it and it seems a bit infiltrated in the base and you will often find you have inadequately excised it. Sometimes old warts can have a solar keratosis or even an SCC arising in a small proportion of the lesion. This is usually seen on the dorsum of the hand, the foot or the extensor surfaces of the forearm and lower leg. Other problem sites include the anterior tibia with shave biopsies where it may be impossible to tell between lichen planus, lichen simplex, keratoacanthoma, SCC and pseudo epitheliomatous hyperplasia. He then went on to talk about melanocytic lesions and the influence of site and the interpretation of these lesions. With acral nevi there are often scattered cells in the upper epidermis and even pigment in the keratin layer. The dermal component is usually discontinuous. Note the presence of pigment in the cornified layer that may present as a discreet column of both cells and pigment. If there is a discreet column like this then it is likely to be a benign lesion, but if the pigment is diffused in the epidermis then it is more likely to be melanoma. He then looked at lesions occurring in the milk line defining this as including the breast, the groin and the periumbilical areas. Vulval nevus often has confluent nests and these nests may go down the adnexa as well. This is not a malignant pattern it is a benign pattern. Periumbilical lesions can be similar but they often have a funny fibrosis in the base considering the origin of the umbilicus and involution of the (vitilome?) umbilical duct. On the thigh the lesion is usually again benign but it may have peculiar features of a Clark or a spitz nevus particularly in women and it can be seen on the thigh of the lateral buttock. It may look like a spitz nevus at the edge but it is not a spitz in the centre. The nevus cells are often small and banal so remember the spitzoid Clark designation of nevi on the thigh in young women. On the abdomen pigmented lesions may be quite broad and because of this even though there is not really any atypia they may be diagnosed as a dysplastic nevus. Many nevi on the upper back have a lentiginous or single cell spread at the junctional and may be diagnosed as lentiginous junctional dysplastic nevi. However these lesions usually have a well defined edge and again it is usually single melanocytic cells along the retie ridges. He did acknowledge that the lentiginous junctional dysplastic nevus on the back is a precursor to melanoma and I must admit that I find it difficult to reconcile this with his description of some of these other lentiginous spreads of melanocytic lesions on the upper back. As this lesion ages it tends to get more nested with bridging of dysplastic nevus like nests but you still have a maturing dermal nevil component. So you have to watch a shave biopsy of this lesion. You need to have the dermal component to make it benign. The other type of nevus on the back is again often quite broad with prominent disparity in the size and the shape of the nests however in this case there is often fibrosis at the centre of the lesion and the lesion itself may be papular and it may have dysplastic bridging at the edges. Nonetheless this is still a benign nevus. Scalp: The nevus on the scalp of a child Again it is usually a broad lesion with some degree of epidermal hyperplasia. There are often spindle nuclei and there is a random nesting pattern. In other words the nests are not just seen at the retie tips. This is probably a type of congenital nevus. You may occasionally get a benign nevus of the scalp where there is as well as the usual nevus another population of melanocytes presenting slightly differently and this is commonly seen in congenital nevi of the scalp. Melanoma on the leg It is usually below the knee in women and there are small cells but occasionally they are larger with monomorphous melanocytes. Essentially there are too many cells per unit area and when you look at this with low scanning there are multiple patterns across a broad front. There is no stromal reaction. Note that atypia and cells that appear to be above the epidermal junction are not good discriminators for a melanoma diagnosis. Melanomas on the legs of women may have some degree of satellite metastasis pattern as well. They appear to have a skip lesion and then new melanoma. Sometimes nevi in children will cause quite marked expansion of the epidermis but if you see this with nests or cells and if you see this in an adult then they shouldn’t occur. So in essence if you have got a monomorphous melanocytic presentation in an adult it is unusually cellular and there is no stromal response to the deep component then this may show a tendency to satellite metastasis locally and it is a melanoma. He also talked about blue nevi of the scalp in people in the mid 50s. He has seen cases of melanoma growing in the substance of the blue nevus and it is many years after the lesion has obviously been there. Many blue nevi are in fact congenital anyway. He also commented on pilar tumours of the scalp such as epidermoid cysts recurring as SCC if bits are left and he feels that blue nevus can in fact subsequently present as melanoma on the scalp. I find the cellular blue nevi are perhaps more common on the scalp. I do not know if they are more likely to form melanoma many years later than normal monomorphous blue nevi. Phil LeBoit then gave a lecture of interface dermatitis and it was an approach based on epidermal changes. This lecture was well covered in the handout that came at the conference and it is probably unnecessary for me to summarise this if you were in fact there. A few clinical points that I gained from it were that if you have someone with lichenoid interface dermatitis over 60 then look for a lichenoid drug eruption but if under 60 it is likely to be lichen planus and note also that lichenoid drug eruptions can take a long while to go away even though the drug is withdrawn. In a lichenoid drug eruption you ……………………… parakeratosis with associated eosinophils and plasma cells as part of the cellular infiltrate not just lymphocytic. He also commented that it is difficult to separate hypertrophic lichen planus, verrucous lupus and SCC. Mycosis fungoides never presents with an anogenital lesion initially but may subsequently. He talked also of secondary syphilis as a mimic of lichen planus and found that immunoperoxidase stains were better than the Warthin Starry stain for demonstrating the treponemal organism. Another point was that if an epidermis with a lichenoid eruption is very thin then it is usually lupus or dermatomyositis rather than lichen planus. Interface reactions may also be seen in lichen planus like keratosis, poikiloderma vasculare atrophicans, regression of a melanoma, regression of a BCC and sometimes of porokeratosis of Mibelli. Occasionally you can even get an MF like keratosis reaction. He also highlighted the problem of misdiagnosing lupus erythematosus if a biopsy is taken from the central region of an area of disseminated superficial actinic porokeratosis. Phil also then went on to present several cases. The first was a neutrophilic urticaria and early lesions of Sweet’s syndrome may look like neutrophilic urticaria. You also have to consider early dermatitis herpetiformis, bite reactions, cellulitis, Still’s disease and erythema annulare centrifugum in your histological differential diagnosis and very rarely the urticarial like lesion of erythropyetic protoporphyria. Note that the pre versicular stage of dermatitis or piriformis often has neutrophils as the infiltrate in the papillary dermis and sometimes you can even have neutrophilic collections. Treatment is usually Dapsone and perhaps colchicine for neutrophilic urticaria. Case 2 was the psoriasiform eruption of a zinc deficiency of acrodermatitis enteropathica. If in an adult it is usually seen in a patient who has Celiac disease. Also necrotic migratory erythema may look very similar. The classic histological feature is the paler of the top layer of cells in the epidermis. Necrolytic acral erythema is another condition that is seen particularly in the Middle East and is associated with hepatitis C and sometimes with zinc deficiency. Case 3 was an atrophic lupus erythematosus. Note the thin epidermis with also an infiltrate around the appendages and quite a marked lichenoid reaction. He talks about Lamisil and subacute cutaneous LE. There were also a variety of other drugs that can cause a similar picture. Drugs that cause subacute cutaneous LE usually have both a positive ANA and a positive SSA and SSB in their immunofluorescence patterns. Particular drugs that can cause subacute cutaneous lupus include the calcium channel blockers, Terbinafine, Ranitidine, Tamoxifen and surprisingly Hydroxychloroquine. Usually subacute LE has a very dense lichenoid infiltrate as against the lichenoid infiltrate that is seen in discoid lupus. Case 4 was a case of cutaneous TB. Note that it is very (pauci?) bacillary and generally the cases that we will tend to see are hypersensitivity reactions or tuberculids. Case 5 was an acute generalised eczematous pustulosis mimicking toxic epidermal necrolysis. We tend to think of AGEP as being a pustular disorder. In other words primarily presenting as pustules but sometimes it will present as a TEN like syndrome. A majority of cases are obviously drug related and the other important thing about this condition is that it occurs very shortly after a drug is introduced. In other words it would not seem to be almost an allergic reaction. The mechanisms are a bit obscure. IV immunoglobulin may be used on treatment. Case 6 was a CD32 cell lymphoma with positive cells only seen in the base of the specimen and the lesion was very neutrophil rich. Case 7 was a case of lichen striatus that he had seen just before coming out here to Australia. Peter Ebeling then spoke on Vitamin D. If your Vitamin D levels go down parathyroid levels go up and it would appear that Vitamin D toxicity is not possible due to sun exposure. One study suggested that one MED body exposure is equivalent to about 15,000 international units of Vitamin D. The optimal level of Vitamin D that we should have is about 75mili mills per litre. Insufficiency is where your levels are between 50 and 75, mild deficiency is between 25 and 50, moderate is between 12.5 and 25 and severe is less than 12.5mili mills per litre. With low levels like this you may get approximal myopathy and quite marked aches and pains. Other factors, which may affect Vitamin D levels include the season, the latitude and probably most of all behavioural factors. Note that certain medications taken for epilepsy will lower Vitamin D levels and they are also particularly low in patients with celiac disease. From the recent lecture from Gary Halliday at the epiderm meeting on immunosuppression from less than 1 MED of ultraviolet light it would appear that the two things that we really need to take if we want to protect ourselves are Nicotinamide to prevent ultraviolet induced immunosuppression to the skin and Vitamin D to help our bones and also perhaps to prevent the development of other cancers. We should take somewhere between 700 and 800 international units of Vitamin D per day but the tablets that are available here in Australia are usually a 1,000 international units per day. In New Zealand you can get tablets that are 50,000 international units of Vitamin D and it is suggested that you need one of these a month. The other concept that was raised by Peter Folley in his talk was that sunlight induced aging is the speeding up of the natural process with shortening of the telomeres and chromosomes and thought that sun aged skin shows this but normal aged skin such as the buttock skin does not. It was also interesting that apparently sub erythemal doses are best at inducing Vitamin D levels rather than having more than 1 MED because at higher levels the sunburn induced by these seems to break down the pre Vitamin D3 so sub erythemal doses are best for both your production of Vitamin D and to minimise your immunosuppression. Vitamin D modification in the skin from pre Vitamin D to Vitamin D3 is best at the lower UVB levels rather than the 310 nanometer level that we use in the treatment of psoriasis or atopic eczema. Make sure you are not getting any extra Vitamin A in with Vitamin D supplements because it tends to counteract the affect to the Vitamin D. It is also suggested that if you are deficient in Vitamin D you take a loading dose of perhaps 5,000 units before taking your 1,000 a day. Dr Gottlieb then spoke about interesting cases from the Academy and by Academy he meant the Acumen Academy of Dermatopathology. First case was of a desmoplastic melanoma. You have to look for a neurotropic component of this melanoma. Case 2 was a case of herpes zoster with destructive inflammation of the hair follicles and removal of the hair follicles. Case 3 was a sebaceous adenoma and he then went on to talk about that and sebaceous carcinoma, the Muir-Torre syndrome and the increase risk of colon and thyroid cancer. You may find a keratoacanthoma like lesion with sebaceous carcinoma at the base. Sebaceous adenoma may not be associated with Muir-Torre syndrome. Case 4 was a combined congenital nevus and one had to compare it with melanoma. Case 5 was chemotherapy induced drug reactions, which may give unexplained diffuse atypia in the epidermis of a skin biopsy. It is due to the chemotherapy that they take. He also said that ……………. bodies were a clue to carcinoma and illustrated it with a case in which they were seen when the patient in fact had breast cancer. Case 7 were linear erythematous bands that are sometimes seen in patients with rheumatoid arthritis. They look like Monge’s disease but they are not a thrombosed vein. It presents with a palisaded interstitial dermatitis often associated with arthritis and it also may be an indication of other collagen diseases. Case 8 was thyroid carcinoma. Case 9 was a young person with neutrophils and sebaceous glands and he called it neutrophilic sebaceous adenitis. He thought it was due to a fat soluble substance that somehow is absorbed into the sebaceous glands and destroys them. Case 10 was a fibrosing septal panniculitis. It was very like erythema nodosum histologically but in point of fact it was nephrogenic fibrosing dermopathy. Case 11 was a case of lymphedema secondary to reflex sympathetic dystrophy and a complex regional pain syndrome. The patient ended up having the hand, which became functionally useless amputated. Phil LeBoit then spoke of some emerging conditions in dermatopathology. He spoke about (Fox Fordie ?) disease with forme histocytes being present. He talked of the tick tack toe sign with infant (dibular?) hyperplasia and telangiectasia seen also in keratosis lichenoides chronica. He spoke of some cases of breast metastases being a hybrid of pyogenic granuloma and metastatic breast tissue. He also showed a case of the amyloid occurring with some cutaneous bone formation. If you see this phenomenon of cutaneous bone formation make sure you stain locally for amyloid because it may be a presentation of systemic amyloidosis. He then talked of some of the pseudo lymphomas especially when some present as a solitary lesion of the head and neck. There may be a type of pleomorphic T-cell lymphoma but there are in fact some cases like this that have no evidence of …………………….. If you have multiple lesions then it is more likely to be a significant problem. He also talked about keratoacanthoma like changes overlying some ductal tumours and Steven Gossards concept of infundibulo cystic hyperplasia. The Brennan Prize presentations were on bacillary angiomatosis and on the different types of melanoma and particularly a patient who presents with diffuse melanosis cutis presenting as diffuse hyperpigmentation. Some usual variants of melanoma were also described including oral melanoma seen in less than 4% of malignant lesions of the mouth. The third presentation was on crypticoccal meningitis in a patient who was on Infliximab and previously on another monoclonal for pustular psoriasis. The Geoffrey Hunter oration was given by Phil LeBoit on dysplastic nevi thesis, antithesis and synthesis. This was a very scholarly lecture on the evolution of the dysplastic nevus entity in term that pointed out some of the fallacies of the concept but in the end go down to the genetic level and showed that in some of these lesions there are in fact genetic abnormalities which are also seen in early melanoma. Mind you as he pointed out there is still a lot of work to be done in analysing the instance of these apparent genetic anomalies in what we would regard morphologically as benign simple nevi. The histological features of dysplastic nevi include fused retie ridges with fibroplasia beneath the retie ridges. There is evidence of a nevus seen in up to 20% of melanomas. If you have 10 or more dysplastic nevi then there is a 12 times increased risk of developing melanoma. If you have one dysplastic nevus or atypical or Clark nevus call it what you will there is two times risk of melanoma. If you have increased numbers of just small and large nevi which are neither clinically atypical or dermatoscopically dysplastic then there is a four times increased risk of melanoma. He also spoke a bit about specialised sites of the body and the morphology and histology of lesions that are seen at these sites. There are the diverse eclipse nevi, which are seen particularly on the scalps of children. They have a dark periphery to the lesion and a clearer centre. You also can have what have been described as spitzoid Clarks nevi on the outer aspect of the thigh. Phil also noted to go back to the genetic features of nevi that B RAF mutations are present in 60% of common nevi. The major factor that appears to be related to melanoma is just density of nevi or the total number of nevus cells that an individual has. So in the area of dysplastic or Clark nevi the clinical ………………type correlates with melanoma risk. In these lesions a degree of what people regard as atypia really means nothing. If an individual is immunosuppressed then this appears to lead to many of these dysplastic nevi erupting and tumour ………………..mutations are also increased in dysplastic or Clark nevi. To go back to immunosuppression with the increase in dysplastic or Clark nevi this is usually a dead end phenomenon. Only some of these lesions ever develop into melanoma so that some individuals with multiple lesions may lack something that keeps their normal nevi under control and they grow and develop into these dysplastic or Clark nevi. So it is the cell number and surface density of these cells that is important and it is acknowledged that they can be mildly genetically unstable. Another way of looking at a dysplastic or Clark nevi is that the nevi in a prolonged state of adolescence. An important take home area of Phil’s lecture on when to re-excise dysplastic nevi. He felt that they should be re-excised if they are growing firstly on sun damaged skin where single melanocytes predominate in the histology and he said particularly to beware of diagnosis of dysplastic nevus on the face that has not been fully excised. He felt that many of these were probably melanoma in situ especially if the predominant histology was junctional. The second reason to re- excise dysplastic nevi is there is marked confluence of the nests. Third reason was if there was pagetoid scatter but no evidence of the nevus having been irritated. Fourthly if there were large melanocytes in the lesion and the lesion was not in a special site or it was not spitzoid. Fifthly if a partial biopsy had been taken of a lesion and it was in a special site and sixthly if there was regression at the edges of the lesion particularly or even elsewhere in the lesion. In summary it was felt that if a dysplastic or Clarks nevus had been biopsied or taken with narrow margins that irrespective of the degree of atypia and in point in fact he did not comment on the level of atypia in these lesions but if there were a lot of single cells with lots of associated elastosis particularly on the face then the lesion should be excised. It was interesting that he did not feel that the degree of atypia in these lesions should be described. Apparently even amongst Pathologists this is a very subjective decision. Day 2 of the Conference began with discussion on cutaneous lymphoma by Phil LeBoit. He initially began with a philosophical discussion on pseudo lymphoma or cutaneous lymphoid hyperplasia where he felt that the histopathology was often just a reiteration of the lymph node and its structure with a formation of lymphoid follicles in the skin. The neoplastic counterpart of this was cutaneous follicular cell lymphoma. The lymphoid follicles in the latter have thinner mantle cell areas around them and less mitosis in the centre of the follicle than say a normal lymphoid follicle and these cells would stain for BCL 2, KI 67 and CE 10. Then there was the marginal zone lymphoma. One often may see anetoderma within these lesions clinically when they present. A key feature is the presence of lympho plasmacytoid lymphocytes looking like plasma cells along the adnexal structures. He then talked about the diffuse large B cell lymphoma. It is usually seen on the lower leg in the elderly. It is BCL2 positive and sometimes these lesions may be misdiagnosed as sarcomas because of the cell structure and shape. The next common lymphoma that clinicians such as Dermatologists will see will be the angiotrophic lymphomas. These generally present as bruise like lesions where the blood vessel lumens are obscured by cells in the vessels and these cells are usually B cells. A simulant is intravascular histiocytosis, which is seen in some patients with rheumatoid arthritis. He then went from the B cell lymphomas onto the T cell lymphomas and commented that the patch stage can last for years especially if less than 10% of the body surface area is involved. Some time was spent discussing digitate dermatosis or whether this in fact should be described as patch stage mycosis fungoides. It was felt that it was best not to include it as such as a lymphoma because of the concern that this arises in a patients mind. As T cell lymphomas develop and as they develop from a patch to a plaque and a nodular stage then patients with these later stages actually die not from the lymphoma but from immune collapse associated with lymphoma. In other words they have no functional T cell even though they have lots of T cells. It was felt that various clinical …………tapes of mycosis fungoides including verrucous, atrophic and pigmented purpuric types are in fact due to the actions of cytokines in the epidermis. When biopsying an early case of suspected patch type T cell lymphoma it is important often to get a series of biopsies. Either a six pack in the form of punch biopsies or sometimes even a shave biopsy to be able to look at a large surface area of the epidermis where most of the action is. So I think that it is important to reiterate again that a shave biopsy might be better here in early patch stage mycosis fungoides. The histological feature that is important in diagnosing this early patch stage mycosis fungoides is that the lymphocytes in the epidermis are larger and have darker nuclei than those that remain in the dermis. The prognosis of patch stage mycosis fungoides does not depend on the immunohisto chemistry or on gene rearrangement studies but in fact it depends on the total surface area involved. So when one has less than 10% surface area involved in patch stage then the long term prognosis is excellent and people will regularly go 30 years or more without it developing any further. He did spend a little bit talking of the pigmented purpuric presentation of some cases of mycosis fungoides particularly the lichenoid purpuric presentation like lichen aureus and also the true pigmented purpuric eruptions particularly this lichenoid type may histologically simulate patch stage mycosis fungoides but the things to look for where the siderophages in the base of the specimen. The critical point in the neoplastic progression in mycosis fungoides is when plaques form from the patches. There is an increase in atypia of the lymphocytes invading the epidermis. These lymphocytes can grow on the connective tissue in the dermis itself and has a deleterious affect on immune response. There is often the presence of eosinophils in the cellular infiltrate and you have variable sized lymphocytes and there is a switch from TH1 to TH2 type immune responses. Another interesting thing that he pointed out was that most cases of mycosis fungoides presenting as follicular mucinosis have little early epidermal involvement. Some cases even can be follicular trophic without mucin formation. Histologically presentations with granulomatous mycosis fungoides did not have distinctive clinical lesions and they appear to have the same prognosis. Granulomatous slack skin diseases are a very distinctive clinical variant of mycosis fungoides and may have a curious relationship to Hodgkin’s disease as well than increased incidence of the latter. Patients present with hanging bags of skin particularly in the axillae and the groin and histologically within the dermis you will see giant cells that basically are gobbling up elastin and hence giving rise to the hanging bags of skin. These patients react badly to surgery and if you try and excise these areas they will just reform. He then spoke of the Worringer Kollop variant of Pagetoid reticulosis particularly seen in younger people on the lower limbs. These lesions show marked epiderma trophism and in some way there seems to be the phenomenon of …………….. up of these large cells in the epidermis rather than the dermis. Sezary’s syndrome presents with generalised erythroderma with hyperkeratosis of the palms and soles and lymphadenopathy. Skin biopsies themselves are not diagnostic of Sezary’s syndrome and really you have to find Sezary cells in the peripheral blood. Hall also pointed out that if you look at most people over the age of 80 5% to 10% of them may in fact have a clonal T cell population in the blood. One needs to find 1,000 Sezary cells or more per mill of blood to make a confident diagnosis of Sezary’s syndrome. He also spoke of the HTLD1 virus T cell lymphoma. It is particularly seen in Southern Japan and other parts of Asia. The characteristic feature is the cloverleaf lymphocyte in the peripheral blood. He then talked of CD30+ lymphomas and the one that we are more likely to see in dermatology is lymphomatoid papulosis. There is often a CD4+ and CD30+ T cell proliferation in the lymphomatoid papulosis but often the diagnosis can only be made with certainty when the patients are followed up over a period of time and the lesions have a finite lifespan and involute. Examples were also shown of patients with lymphomatoid papulosis occurring on a background of lesions of more typical patch stage mycosis fungoides. The CD30 stain lights up the large cells in this condition and he reiterated again the importance of clinical observation of a patient’s progress in making a confident diagnosis of lymphomatoid papulosis. You can get cutaneous Hodgkin’s disease but it is usually skin spread from systemic disease and it is not common. They also talked about some of the subcutaneous lymphomas particularly subcutaneous panniculitic like T cell lymphoma. He said this was a particularly dangerous area because it is usually initially misdiagnosed as an inflammatory panniculitis particularly lupus profundus and these patients may have in fact a very high ANA. They often though develop an erythrophagacytic syndrome and the patient becomes panocytopenic. Ringing of adiposities may be found in this lymphoma by the involved T cells. The CD56 positive natural killer cell lymphoma is usually of the nasal type that may also be seen with disease on the extremities. Epstein Barr virus may also be seen commonly in these lymphomas. Dr Deborah Norris then spoke of cutaneous lymphomas highlighting pitfalls in immuno histochemistry. This was an excellent lecture for the dermatopathologist present especially those who do a lot of immunoperoxidase staining. She reiterated that it was important to do targeted staining rather than a whole battery of these stains and then try to interpret things. This was a difficult lecture for a Dermatologist to fully appreciate. The main things that I picked up were that CD30 is a marker of activation of lymphocytes and it can commonly be seen in conditions such as insect bite reactions, drug reactions, herpes simplex and zoster infections and other infections particularly scabies, orf and other viral disorders. Methotrexate induced lymphoproliferative disease often have the EB virus found as well and 60% of these sort of cases regress when Methotrexate is withdrawn. She also talked about the immuno queevey website where one can look up the likely diagnosis for certain combinations of immuno staining results. Most of Dr Norris’s lecture is in fact contained in an excellent handout, which she gave in the Conference handbook. Dr Grant Jenkins an Infectious Diseases Physician than gave an excellent presentation on microbacterium ulcerans also known as the Bairnsdale ulcer. Microbacterium ulcerans is the commonest microbacterial disease that we will see after TB and leprosy. You can get a pre ulcerative nodule with a fair degree of subcutaneous involvement in this condition but more commonly you see usually papules, which subsequently progress to ulceration. In the initial histology of these lesions granulomas aren’t prominent. This is because the microbacterium ulcerans makes a toxin, which is both cytotoxic and immunosuppressive and in part is due to the extensive subcutaneous involvement that you will get with this particular organism. Dr Jenkins also showed some excellent images of the acute oedematous variant or cellulitic like variant of this condition which extensively involves the subcutaneous tissue before much ever happens in the overlying epidermis. Culture of microbacterium ulcerans often take six to eight weeks and is relatively insensitive. He explained how important the PCR test is in making a diagnosis and it can be done even on a swab of an ulcerated lesion rather than on tissue. The PCR is very sensitive and very specific. The techniques are able to extrapolate on 100 th of an organism and build it up because of the insertion sequences that are seen in this particular organism. It will even work on formalised tissue as well. Note that the treatment of choice in microbacterium ulcerans is in fact excision of the involved area and either flaps or grafts so it is important to make this diagnosis early. You can in fact aspirate pre ulcerative lesions if you are looking for tissue in which to do the PCR. The cost of the PCR is only about $25.00. The Clinical gems section following with Dr John Snow showing a case of secondary syphilis his point being that the immuno stains for spirochetes were in fact much more sensitive than the Warthin Starry stain where it was difficult to pick up the thread like spirochetes against a black background of other staining with this stain. A case of chronic cutaneous microbacterium marinum infection was then presented by Dr Ellen Ma. This patient probably acquired this disease when he was a boy in Fiji about 50 years ago and he presented now with multiple pigmented nodules on his left limb. He was treated with oral Clarithromycin and Vitamin D supplementation and the case represented the longest cutaneous microbacterium marinum infection known. Dr Delwyn Dyall-Smith then presented a case of palisading necrobiotic granulomas in the HIV+ patient. Clinically these lesions look like rheumatoid nodules. Histologically they had a granuloma annulare like presentation in a patient who was not known to be HIV+. She was subsequently found to be HIV+ with a very high fyrol and low CD4 count but the source of her infection was not known. The skin lesions were responding to HAART therapy. Dr Myles Prince spoke on the treatment of cutaneous T cell lymphoma. This was a very detailed lecture looking at a series of investigational drugs that have been used in the Melbourne Lymphoma Group to treat various types of lymphoma. The notes that I made were to watch the CD30+ large cell transformation of mycosis fungoides. If it is localised in a single nodule that develops against a background of patch stage MF then basically just treat conservatively and either excise the nodule or treat with radiotherapy. If it is generalised then aggressive chemotherapy is in fact required. He pointed that there was a distinction between erythrodermic mycosis fungoides and Sezary’s syndrome and that erythrodermic mycosis fungoides is less of a problem than actual Sezary’s disease. The risk of CD30+ large cell transformation for early stage mycosis fungoides is only about 0.4%. He also pointed to the relative immune suppression in some people with lymphomas and the change in …………….type from TH1 to TH2 responses. He also advocated Methotrexate for lymphomatoid papulosis but the doses that are required are not the sort of homeopathic 5mg per week doses but 20mg to 30mg on a weekly basis. He spoke also of the use of Bexarotene or Targetin this is a Retinoid and it is useful in some of the T cell lymphomas. The concept also of having diphtheria toxin linked to an IL2 receptor protein that will attack the IL2 receptor on T cells was also reiterated as a means of targeted destruction of T cells and the last group of drugs that he talked about were the Histone and (Diasetilator?) inhibitors which can both switch on and off genes by putting the DNA material back on the Histones and switching it off by making it difficult to be read and switching it on by unravelling it again. These drugs may even have a place in early patch stage mycosis fungoides and we will probably hear more about them in the hear future because they are pretty safe drugs and they have a very good side affect profile. Some thalidomide like drugs are also being trialled in T cell lymphomas. Phil LeBoit then spoke on genomic insights into the nature and diagnosis of melanoma. He indicated that many new investigative techniques of a genetic basis were being used to look at the lymphomas and the one he spoke mainly on was comparative genome hybridisation where there may be a growth increase or even loss in parts of chromosomes. A technique of fluorescent in situ hybridisation is then used to see the number of copy number mutations or changes that have occurred and where they have occurred. There may be an amplification in the number of ……………………….of these chromosomes. In melanoma there are both losses and gains of DNA over various chromosomes including chromosome 6 and 9. He commented that proliferating nodules in congenital nevi do not necessary develop as a melanoma even though histologically they may look like melanomas and often with a five year follow up of these sort of cases no melanomatous metastases developed if there were a few mitoses in the lesions. There are usually gains or losses of whole chromosomes in these lesions rather than just localised amplifications of genes. They looked at comparative genomic hybridisation in Spitz nevi. In benign nevi you really find nothing when you look for these but in Spitz nevi there are often gains on the 11P Chromosome and losses of the 9P chromosome. 20% of Spitz nevi may show 11P changes but most of these are in fact seen as Spitz nevi that are not difficult to diagnose anyway. You ask the question of: Do melanomas arise in Spitz nevi? You generally do not see pagetoid spread in the epidermis in a pre pubertal child with melanoma. B raf is absent in Spitz nevi. Geoff Gottlieb then gave an excellent hour long lecture on an algorithmic approach to the diagnosis of melanocytic lesions or melanoma. There was a progression from benign to malignant and the four things that they looked for were the size of the lesion, symmetry of the lesion, circumscription and that there was no maturation. Generally if a lesion is well circumscribed it will end with a complete nest rather than tailing off with single cells into the surrounding epidermis. A major fact he emphasised was that in an adult sheets of melanocytes tends to suggest melanoma. There are basically too many cells. Another point was that a thick lesion with some degree of normal elastosis below it suggests that the lesion has been there for some time, i.e. there has been filtering of ultraviolet light. If there is downward displacement of upper layer type solar elastosis into a lower level then this suggests that it is a new lesion that has pushed the previously damaged elastotic tissue down lower. Small lesions less than 4mm are almost invariably benign. So are large lesions that are symmetrical. Large lesions that are asymmetrical and well circumscribed again are often benign but those that are poorly circumscribed which still show some degree of maturation may be either a melanoma or a nevus but those with no maturation at the base they are almost always melanoma. Of course there are exceptions to all of these and he spent some time looking at these exceptions. The criteria for exceptions included melanocytes above the derma epidermal junction, variations in the size and shapes and confluence of nests in atypia. When they were seen even with small lesions he suggested that the small lesion might be a melanoma. Certain anatomical sites made it more likely that a particular lesion that may be large and asymmetrical may in fact be benign. Mitoses don’t always mean that a lesion is malignant but he number of mitoses is of some importance. The greater the number the more you take notice that it may be a malignant lesion. As he had explained in his very first lecture of the Conference the sites and dermoscopy of a lesion may cause the Pathologist to reinterpret. If you have a Spitz nevus it negates other worrying features so that the type of nevus can be an important criteria for exceptions to the algorithm. A combined congenital nevus can be another exception where a papule that is biopsied is included with a different cell population. Generally in these circumstances the other cell population is interacting with the underlying cell population and not displacing it. If one set of cells displaces another set of cells then it is more likely to be a melanoma than a combined congenital nevus. He then talked about a residual or recurrent nevus. In this often the cells are confined to the scar itself because the scar when its reformed when something has been partially shaved is in fact repopulated by nevus cells that come from the base of the shaved lesion. This was a very good lecture in which he showed several examples to illustrate these criteria for exceptions to the underlying simple algorithmic features that he described. Peter Sawyer then gave a talk on the case for a combined diagnostic approach using both histopathology and dermatoscopic evaluation of lesions. Some technical points made in his lecture were that the method of cutting acral lesions should be changed so that one cuts along the line of the dermato glyphics because often the more typical cut at right angles to this will give the impression of melanocytic cells in the epidermis and tend to over call these as melanomas. He talked a bit about tape stripping of lesions that have quite marked central hyperpigmentation because then you can remove the pigmented parakeratotic cells that are in the stratum corneum and allow you to see the network underlying the lesion and the fact that it is generally benign. He talked a bit about confocal microscopy and the fact that it is like a horizontal section of the skin. It does not though penetrate terribly deep into the skin only to about 200micrometers and so it is mainly used for superficial epidermal lesions particularly a lentigo maligna. Generally you find that cases, which are equivocal dermatoscopically are also equivocal pathologically so the dermatoscopic picture is a visual representation of what the Pathologist will see. He ended the lecture with a discussion of a paper that is due to published which looked at the degree of change of a Pathologist’s diagnosis related to the amount of additional information that he was presented with including such factors as the age of the patient, the site of the lesion, the dermatoscopic image, the clinical image and the finding was that the more information that was in fact given to some histopathologists especially those who also had a background in dermoscopy then the more accurate the diagnosis became, the degree of change though varied from Pathologist to Pathologist. Then followed a melanocytic lesion responder session chaired by Martin Haskett with cases provided by John Kelly from the Melbourne Melanoma Unit. This was an excellent teaching exercise in which one had to respond fairly quickly with ones degree of concern for a clinical image, the dermatoscopic image and subsequently the histological image of a lesion and state whether one thought it was benign or malignant. The dermatoscopic features often caused Dermatologists to either consolidate or change their opinion much more than Pathologists whereas obviously the histopathological image was a major factor in influencing the final diagnosis of Pathologists. Some dermatoscopic images were shown with an inverse network, which was quoted as being about 22% specific for a diagnosis of melanoma but 95% sensitive in the diagnosis of melanoma. A take home message was given at the end of each of the 12 cases that was presented and some of them were that any change in a body map image of a lesion deserves histological assessment of that lesion. Two clinical images that looked remarkably alike the Reid nevus were presented, one was in fact a Reid spindle cell nevus but the other was a melanoma although there was some discussion from the audience on this. In general in melanoma the radial streaking that you see at the edge will extend back into the body of the lesion rather than just being at the periphery, which tends to be a feature more seen in the variant of a Spitz nevus. The ridge pattern of an acral lesion was particularly obvious in the dermatoscopic image to Dermatologists in allowing them to say that this acral lesion was a melanoma. A particularly good case of desmoplastic melanoma was presented where the only dermatoscopic features were some dotted vessels and smudged pigmentation. The lesion had been biopsied before and reported then as a sclerotic nevus. The take home message here was that if you have any new lesion that you think in fact is a dermatofibroma clinically then in the absence of a history of it being there for quite some time you should biopsy and it needs to be a good punch biopsy or an excisional biopsy. Desmoplastic melanomas are still one of those melanomas that we find very late and its evolution and this leads to these lesions being a lot thicker then they should be before they are picked up. Not a particularly nice case of nodular melanoma that initially looked like a hemangioma was presented and was also a good case of superficial spreading melanoma in the conchal bowl. The Steven Cossard lecture was presented by Geoff Gottlieb and it was on the folk law of melanocytic neoplasia. He started off by commenting on excision margins for pigmented lesions and commented that these were really just arbitrary numbers that were initially put forward and that there is no evidence base for them but he spent most of the talk doing an analysis of the theory of sentinel lymph node biopsy and a particularly good forensic analysis of the paper published in 2006 in the New England Journal of Medicine by Morton where subset analysis of the data was done to try and prove a survival benefit for this procedure. His main criticism was that only half the data was used for a prognosis analysis of this subset and that various errors could have been present in this data including wrong diagnosis which would have been balanced out if the other subset of the data had been included but not when selectively chosen like this. The purported 5 year difference in survival rate when this half data subset was looked at was a difference of 72% versus 90%. This was not a significant enough difference even allowing the analysis for the data to go unchallenged to make it worthwhile to carry out the procedure. He also raised the issue of whether these lymph nodes in fact have a preventative function in stopping metastasis elsewhere in the body and used the data to point out that there does in fact appear to be a better long term result in those patients who in fact did not undergo elective lymph node dissection and that this benefit could be as much as 20% relative to the other group who did. The fact that melanocytes are found in the lymph nodes does not mean metastatic disease. You can often in fact see cell nests in nodes. This is particularly seen in congenital nevi and also has been seen in blue nevi on the buttocks. This report does not really give an adequate description as to how good his forensic examination of this paper was. It is probably the best exposition I have seen on the futility of sentinel lymph node biopsy in melanoma. Whether the concept is valid in other tumours such as Merkel cell and breast cancer remains to be seen. Dr Phil LeBoit then spoke again on pitfalls in the diagnosis of melanoma with emphasis on lentigo maligna and nevoid melanoma. He began by saying that the era of casualness in the approach to lentigo maligna should come to an end. His major list of pitfalls were: 1. Not recognising that a lesion is fundamentally melanocytic. 2. An over diagnosis of pathology due to the increased number or size of melanocytes in chronically sun damaged skin. The term actinic melanocytosis had been used to describe this phenomenon but he was not a great fan of it. He also felt that there was an over diagnosis of melanoma in situ if special stains immunoperoxidase stains were in fact done. In some of these cases where you are not sure where the lesion ends and the background larger melanocytes are seen that you should do punch biopsies at either side of the lesion and see if they are the same. If they are then that really is just the normal skin for that patient. 3. His third pitfall was enlargement of melanocytes around a lesion that had previously been biopsied. These large melanocytes are seen often at the edge of the biopsied area and this is a false positive. 4. His fourth pitfall was recurrence of melanoma and this clinical point was that the margins of excision need to be wider if the pigmentation is indistinct at the edge of a lesion. And margins also need to be wider if inflammation present of a lesion. Acral melanoma can have cells two to three retie ridges beyond the obvious margins even microscopically when these lesions are then checked with in situ hybridisation study for increased copy numbers of chromosome 9 so this is why acral melanomas should certainly be excised with reasonable margins to pick up these subclinical changed cells and even sub microscopically changed cells. 5. His fifth pitfall was a failure to recognise when too much is too much. 6. His sixth point was that mitoses do not a melanoma make. 7. His seventh pitfall was the internet and the ease with which images can be sent from one person to another but unless you get a chance to look at the original block and the original slides it is often very difficult to make an accurate diagnosis. 8. His eighth pitfall was that inflammation can alter the appearance of a benign nevus. The example he quoted was the Myerson nevus where there is a dermatitic reaction around an otherwise benign nevus. The inflammation may alter epidermal keratinocyte genesis and may give the appearance of melanoma cells in the epidermis and hence you can overcall the nevus as malignant. In hallo nevi or a ………..hallo nevi large outlying nests that are not being attacked by lymphocytes are a worrying feature and might make you consider that this could be a melanoma that is having a hallo affect. Other inflammatory simulants of melanoma include the associations of lichen sclerosis and vulval nevi. 9. This is where you have a melanoma with small cells at the base of the lesion and little epidermal scatter. 10. Do not get too fancy in making a diagnosis. David Ellis gave an excellent talk on clues in the diagnosis of cutaneous lymphoma. Anyone who includes an extract from the Life of Brian in his talk gets full marks from me. He basically showed the naughty boy scene where Eric Idle plays the messiahs mother and screams to the waiting car that he is not the messiah he is just a very naughty boy. With the T cell lymphomas that we see in practice mycosis fungoides accounts for about 48% of them with a 3D30+ ……………..lymphoma the next most prominent group and that includes lymphomatoid papulosis. David talked about two neurons the Archimedes neuron where you just look at something blink and say eureka I know what that is and the holmesian neuron where it takes a series of deductions to make a diagnosis. Very often with lymphoma it is the holmesian maximum neuron that has to work because it is only by doing a series of immunoperoxidase stains and looking at algorithms that you can often put the diagnosis to bed. He commented that lymphomatoid contact dermatitis and lymphomatoid drug reactions were both very naughty boys that can simulate a lymphoma. There also may be problems in differentiating Sezary’s syndrome from a lichenoid drug reaction versus lichenoid erythroderma. Other points I picked up are that you may get a single clone in a T cell lymphoma that does not mean too much at all. Gene scan is a technique that often shows several clones in separate samples but these clones are identical. I had previously thought that a T cell lymphoma only had one clone of T cells but it appears as if there can be several clones but they are identical clones. He then illustrated his algorithm by going through several cases one of which was a marginal zone lymphoma. In crossties lymphoma inside out follicles may be seen histologically. Lymphomatoid granulomatosis may also be another simulant of lymphoma and the CD4+ small pleomorphic T cell lymphoma can be a very naughty boy. This was an excellent lecture for Pathologists but I have to admit a lot of the immunoperoxidase stains and the significance was a bit beyond me. Melanoma Guidelines 2008 These were discussed by Dr John Kelly and Dr Peter Heenan. The overall lifetime risk of in situ or invasive melanoma in Australia is about 1 in 20. A 70 year old Australian has an 8 times increased risk of getting a melanoma than a 30 year old and the risk ratio is even greater in men than in women. The estimated risk factors are that a previous melanoma gives you a relative risk increase of 10. A large number of nevi has a risk factor of 6 to 7. Dysplastic nevi gives you a risk factor of 6 to 7. Non melanoma skin cancers have a risk factor of 4 and there is a family history where if it is a close relative it will double the risk and there is a 1.7 relative risk for each affected member. The CDKN2A gene mutation is one of the commonest gene mutations in melanoma. If three first degree relatives get melanoma and you examine these families then 5% will have findings of this gene mutation in Australia. John went through various recommendations. I have only made a note of some that caught my eye. Total body photography is recommended for high risk individuals with a six month full body examination. There was level 3 evidence for this. Level A being the most secure. The sensitivity of dermoscopy in diagnosing melanoma was 10% higher than the naked eye but it was not quite as good in the specificity. Hence one of the new recommendations is that training is recommended in dermoscopy for clinicians who are practicing in the field and examining skin lesions and a met analysis of public studies said that there was …………day evidence for this. Most of the studies on automated diagnosis had verification biases built into them and hence the evidence was not good. With total body photography no studies actually had a comparison arm done so this weakened the evidence quite a bit and it was only Level 4 evidence. On the question of biopsy it was recommended there be complete excision of pigmented lesions with 2mm margins where there is a suspicion of melanoma. But it was also commented that partial biopsies are acceptable where suspicion of melanoma is low. It was also thought good practice to refer both clinical and dermatoscopic photos to a Pathologist to increase the information that they have in assessing pigmented lesions. Alex Chamberlain then gave a talk on nodular melanoma on the clinical and dermoscopic features. Nodular melanomas have to have a very distinct with rapid growth and they differ from the superficial spreading in that respect. They are normally seen in older men particularly the head, neck, lower limb and back. The way they grow and the rapidity of growth suggests that there may be a divergent pathway for nodular melanoma and melanoma development. Chronic UV damage is associated with nodular melanoma whereas superficial spreading is more associated with intermittent blasts of UV. A nodular melanoma can grow at 0.49mm a month with vertical growth whereas a superficial melanoma may only grow at 0.12mm per month. 60% of nodular melanomas are pink or red rather than pigmented. Only rarely are they crusted. Ignore the presence of terminal hair in these lesions because it does not signify that the lesion is likely to be benign. Most nodular melanomas are firm and rapidly growing. The ABCD criteria do not work and one has to use EF and G. Elevated, firm and growing to help to pick up nodular melanoma. Alex then went through some of the dermoscopic features in nodular melanoma including the milky pink background colour, the polymorphous vessels and polarising dermoscopy to show chrysalids. Most nodular melanomas do have a small degree of pigment associated with them even when they appear amelanotic so one should consider non pigmented nodules very carefully. You do not monitor a nodular lesion, if you have doubts about a nodular lesion you cut it out. Dr Richard Scoliar gave a lecture on subungual melanoma. There is often a late presentation of this condition for various reasons. He was recommending biopsy at an earlier stage. 23% of Japanese melanomas are in fact acral but that is because they get fewer of the other types whereas here in Australia at the Sydney Melanoma Unit the incidence of acral melanomas is 0.4% because there are so many of the other types. Richard commented that the nail plate is a strong barrier to UVB but it certainly isn’t to UVA because we get photo onycholysis which is separation of the nail from the nail bed often due to a photo drug reaction so UVA certainly is able to penetrate and UVA may well be responsible for melanomatous change in nevus or melanocytes. The most superficial part of the nail plate is derived from the most proximal part of the nail matrix. The deepest part of the nail plate is from the most distal part of the nail matrix. The proximal nail plate has very little nail actually over it. In fact you only have a squamous epithelium. There are various other causes of subungual pigmentation ranging from haemorrhage through drugs and fungal infection. The dermoscopy of a subungual melanoma shows irregular width and spacing of the bands. There is often varying colours. If you have had subungual haemorrhage then look at the proximal area near the lunular as it grows out because this area of nail should not have any pigment in it. There should be a clear area between the proximal edge of the cuticle all the time. Subungual melanomas seen in the Sydney Melanoma Unit have on average a thickness of 3.2mm and 80% are Clark Level 4 or 5. These figures obviously mean that you are going to get a poor prognosis. Richard then gave a comparison of the features of acral nevi versus subungual melanoma. Subungual nevi are seen in about 12% of longitudinal melanonychia but it is as high as 50% in childhood. They are usually due to nevus cells in the neo matrix. A subungual melanoma usually has infiltrated lymphocytes present and the infiltrate is adjacent to the subungual melanoma in direct association with the cells. This feature is uncommon in acral nevi. Features that favour melanoma versus nevus are severe atypia, an inflammatory hallo, lymphocytes within the lesion, architectural disorder, a much greater density of cells and haphazard pagetory spread which is seen higher in the nail and is a late phenomenon. A subungual lentigo generally gives a mild increase in melanocytes and an increase in the pigmentation in keratinocytes. Dermoscopy shows a grey pigmentation and fine grey stripes that do not change. Note again the greater density of cells in a subungual melanoma versus the nevus. Complete stretches of single melanoma cells can be seen like a tombstone. They are often multi nucleated melanocytes. There may be lichenoid inflammation and atypia. When gene studies are done on acral melanomas the peripheral edges that may just be melanoma in situ in fact if you have genetic analysis done you find that it may extend between 4mm and 6mm beyond the edge of where you think the lesion ends. This indicates why these lesions have to be taken out with wide margins or recurrence is likely. Steven Cossard looked at the similarities between reaction patterns in the skin and the mucosal surfaces. He particularly looked at the psoriasiform pattern, the lymphocytic lichenoid pattern and spongiosis. Note that spongiosis can be induced by both irritation, infection and allergy and is characterised by neutrophils and eosinophils. Contact dermatitis though in the mouth is a lichenoid reaction and in the skin is a spongiotic reaction. Eosinophilic and neutrophilic spongiosis though can occur in both the mouth and the skin. He then looked at the concentrations of desmal ……………1 and 3 in both mucosal surfaces of the mouth and in the skin in both pemphigus foliaceus and pemphigus vulgaris. Pemphigus vulgaris regularly gives ulceration in the mouth whereas pemphigus foliaceus does not and it is due to the different desmal …………that has antibodies to it in these conditions. There is also varying levels within the skin in the situation of the desmal……………..with desmal ……………3 being deeper in the skin than desma ……………..1. He thought the geographic tongue was not really an association with psoriasis. The lichenoid pattern was often expressed both in the mouth and on the skin. Even contact sensitivity reactions in the mouth tend to be lichenoid for example mercury and amalgam. In the mouth if you have some associated acantholysis as well as a lichenoid reaction consider that this might be paraneoplastic pemphigus. In lichenoid reactions the pathology is likely to be autoimmune. With psoriasiform reactions it is likely to be the ……………….immune system acting and the spongiotic reactions he felt it was delayed immunity type 4 reactions that were important. Most lichenoid reactions are type 2 reactions. The oral mucosa is an area for the induction of immune tolerance suggesting that there is a difference in androgen handling. Toll like receptors and neutrophilic pattern are associated with the psoriatic reaction pattern. Toll like receptors can stimulate the acquired immune system as well. These receptors are generally associated with bacterial infection or a part of the ………… immune system. The clinical gem section then had several presenters. There was a case of CK20+ extramammary Paget’s of the urothelial type having a poor prognosis. The second clinical gem was on VIN. It was commented the warty basaloid VIN is the commonest type of VIN but it only causes less than 20% of the invasive SCCs seen in this condition. Adequate biopsies are necessary to be inclusive of the depth of the lesion to try and pick up any cases of VIN that may be forming invasive SCCs. Shave biopsies are not acceptable. John Snow presented a case of an unusual fungal infection showing sporotrichoid spread. Commented that histologically histiocytes plus small collections of neutrophils basically equals infection. There was an excellent talk on scleromyxedema being treated with high dose intravenous immunoglobulin. The condition began as lichen myxedematosus and subsequently evolved into scleromyxedema. Other differentials to be considered in these presentations include nephrogenic fibrosing dermopathy, system sclerosis and amyloidosis. The intravenous immunoglobulin dose used was 0.4 grams daily for four weeks. IVIG appears to have anti …………….type antibodies in it and it may play a part in clearing the abnormal antibody seen in scleromyxedema. There was an interesting case of a nasal glioma which is ectopic brain tissue it is firm and non pulsatile. The differential diagnosis includes other cysts and vascular tumours but particularly an encephalocele. Generally encephalocele’s will communicate with the skull vault and they will tend to enlarge with crying. The bone adjacent to the nasal glioma was often very thin and occasionally a fibrous stalk may extend to the cranial cavity but there does not appear to be any bony defect. There was a case of primary cutaneous angioimmunoblastic T cell lymphoma with no signs of system disease, an initial diagnosis of granuloma faciali was made because the lesions occurred on the face and had a gren zone. The cell of origin of this condition appears to be the follicular helper T cell, CXCL13 is a marker for it. When studies were done on biopsies from different areas there was the same T cell clone in different sites and times. Low dose Methotrexate was used at 5mg per week and the patient improved dramatically and cleared. There was a good case presented of lipo dermatosclerosis having some great images. The other name for this is sclerosing panniculitis. 68% of cases of significant venous abnormalities may have had previous DVTs. Histologically the phases may be divided into an early, intermediate and late phase, the late phase being characterised by fat microcysts with membranous changes. When treatment is just with compression stockings, some cases can be due to disorders of fibrinolysis and there is often a small vessel vasculitis. Stanozolol can be effective treatment. The last case was one of primary cutaneous angio plasma cellular hyperplasia. Apparently there has only been one other case reported in literature. This case presented as a fairly nondescript nodule on the neck. I have no doubt if I see anything similar in the future I will probably shave it off as a presumptive SCC and it would probably need a pathologist of David Weedon’s stature to diagnose this particular angio plasma cellular hyperplasia condition as well.