Rook random Flashcards

Question

What techniques are there to assist with the subclinical extension of LM or LMM?

Answer 1

Options include standard excision with side-to-side closure versus delayed reconstruction to allow for permanent section margin analysis; Mohs surgery with immunostaining; and permanent sectioning mapped (i.e. ‘slow Mohs’) or staged mapped (i.e. ‘square’) techniques. Consistent with staged permanent section margin methods, studies of Mohs surgery with immunohistochemistry report 0.9–1.5cm surgical margins were histological margin tumour-free in 95–97% of melanoma in situ lesions on the head and neck, with a 0.5cm margin clearing 65% of these lesions

Answer 2

T Simultaneous inhibition of BRAF and MEK improves response rates and survival compared with BRAF inhibition alone. The addition of MEK inhibition not only improves survival, it also reduces resistance development and decreases the cutaneous toxicity seen with single-agent BRAF inhibition Available oral combinations include dabrafenib plus trametinib, vemurafenib plus cobimetinib and encorafenib plus binimetinib. Relevant prognostic factors include lactate dehydrogenase, higher performance status and less than three organ sites with metastases. In contrast to immunotherapy, targeted therapy is generally administered indefinitely. Discontinuation of targeted therapy might lead to tumour regrowth. Interestingly, however, data also suggest that resistance to targeted therapy maybe partially reversed by intermittent dosing or by drug holiday

Answer 3

T Only approximately one-third of melanomas with KIT mutations are responsive to targeted therapy.

Answer 4

T For melanoma patients harbouring a BRAF mutation, targeted therapy with BRAF and MEK inhibitors (dabrafenib plus trametinib, vemurafenib plus cobimetinib or encorafenib plus binimetinib) is an additional valu- able treatment option that is recommended as a second line option except in symptomatic patients

Answer 5

Merkel cell carcinoma (MCC) is a highly aggressive carcinoma of the skin with neuroendocrine differentiation demonstrating high rates of recurrence and metastasis. Indeed, the 5-year rate for MCC-specific survival in the USA is only about 76% for localised, 53% for regional and 19% for distant disease.

Answer 6

T The mean age of patients at the time of initial diagnosis is above 70 years. Notably, there is a 5–10-fold increase in incidence after the age of 65.

Answer 7

T Indeed, the mean age at diagnosis in organ transplant recipients is almost 20 years lower compared with immunocompetent patients. In organ transplant recipients, MCCs tend to develop 7–8 years post-transplantation and affect the head and neck areas, often in the presence of other UV-induced skin cancers.

Answer 8

T Immune control of MCC is supported by a number of observations. For example, MCC occurs more frequently and at younger ages in severely immunocompromised populations, such as organ transplant patients, patients with haematolymphoid disor-ders or human immunodeficiency virus (HIV) infected individuals. Immunocompromised patients also have a worse prognosis. The observation that the incidence rates for MCCs increase for persons living in areas of lower latitudes, and that MCC is most often found on the sun-exposed skin of white people, suggest UV exposure as one of the major environmental risk factors

Answer 9

T In addition, detection of high tumour mutation burden, prominent UV signature and frequent association with squamous cell carcinoma and precursors support an epidermal origin for MCPyV-negative MCC

Answer 10

T Histological features of the tumours associated with poor outcome include tumour size (≥5 mm), extension into the subcutaneous tissue, vascular invasion and a blurred boundary.

Answer 11

T By contrast, expressions of thyroid transcription factor 1 (TTF-1) and cytokeratin 7 are frequently observed in extracutaneous cases, and are restricted to only a small subset of MCC (<10%)

Answer 12

Thus, the predominant sites are the head and neck (more than half of cases) and extremities (one-third of cases), whereas the trunk as well as the oral and genital mucosa are involved in less than 10% of cases.

Answer 13

In contrast, satellite metastases are frequently observed

Answer 14

In addition to the prognostic histopathological markers discussed earlier, several favourable prognostic factors have been identified, including primary tumour size ≤2 cm, local disease, female gender and primary tumour localised on the upper limb. In addition, several studies confirmed the prognostic significance of unim-paired immune function. However, lymph node status is the most important independent predictor including occult microscopic nodal involvement, which is present in one-third of patients The T category is classified by measuring the maximum dimen-sion of the primary tumour: 2 cm or less (T1), more than 2 but less than 5 cm (T2) and more than 5 cm (T3); extracutaneous invasion into bone, muscle, fascia or cartilage is classified as T4. Increasing tumour size is associated with a modestly poorer prognosis The N category is related to the nodal tumour burden. Due to the high propensity for clinically inapparent lymph node metas-tases, true lymph node negativity by pathological evaluation (pN0) alludes to a better prognosis compared with patients whose lymph nodes are only evaluated by clinical or ultrasound examination (cN0). N1a represents microscopic and N1b macroscopic (i.e. clini-cally apparent) lymph node metastases. N2 refers to the presence of in-transit metastases. The M category for distant metastatic disease comprises three (b) groups: M1a includes distant skin, subcutaneous tissues or lymph nodes; M1b is lung; and M1c all other visceral organ sites or brain metastases.

Answer 15

After a confirmed diagnosis of a primary MCC, clinically indicated imaging may be useful in identifying distant metastases considering the metastatic potential of this tumour. In general, it is currently rec-ommended to perform at least an ultrasound of the draining lymph nodes and the abdomen as well as a chest X-ray. It should be noted, however, that the main value of chest X-ray at the time of diagnosis is to provide a basis of comparison for future diagnostics. Positron emission tomography/computed tomography (PET/CT) scanning is gaining importance in diagnostic imaging of MCC and may be preferred even at initial diagnosis. Due to the high frequency of lymphatic metastases, sentinel lymph node biopsy (SLNB) is generally advised to allow pathological evaluation of the sentinel lymph nodes, especially since micrometastases seem to denote poorer prognosis. When distant metastases are suspected, the appropriate organ imaging should be performed. The most frequently involved organ systems are the skin, lymphatics and liver; however, all organ systems may be potentially affected including the central nervous system. Somatostatin-receptor scintigraphy is not well suited for determin-ing disease spread; the usefulness of DOTATOC (DOTA0-Phe1-Tyr3 octreotid) and fluorodeoxyglucose (FDG) PET/CT scans has not yet been conclusively shown, although recent studies suggest their high sensitivity in detecting organ metastases

Answer 16

Given the very high rate of lymphogenous metastasis of MCC in the head and neck region, an SLNB should not be performed, but rather a functional neck dissection should be considered

Answer 17

If an R0 resection is not possible in locoregional tumour manifes-tations, RT may be considered. The total dose for adjuvant treatment is ≥50 Gy with a single dose of 2 Gy five times a week

Answer 18

germline mutations in patched-1 (PTCH1), a segment polarity gene (9q22.3) with tumour suppressor functions. PTCH1 encodes a 12-pass putative trans- membrane protein, which acts like the receptor of the diffusible morphogenprotein sonic hedgehog (SHH) originally identified in the fruitfly Drosophila melanogaster

Answer 19

PTCH1 acts as a tumour suppressor, repressing the G-protein-coupled receptor smoothened (Smo). Loss-of-function mutations of PTCH1 result in reduced suppression of Smo which activates the Gli family of transcription factors and promotes their importation into the nucleus, resulting in sustained activation of target genes. Gli proteins are bound by Sufu, loss of which produces constitutive activation of Gli. Atypical protein kinase C iota/lambda (aPKC-ι/λ), a novel Gli regulator, and its polarity signalling partners co-localise at the centrosome and form a complex with missing-in-metastasis (MIM) a scaffolding protein that potentiates Hh signalling. Activated aPKC-ι/λ is upregulated in Smo-inhibitor-resistant tumours and targeting aPKC-ι/λ suppresses signalling and growth of resistant BCC cell lines

Answer 20

Morphoeic BCCs account for 5% of all BCCs, have ill-defined borders, can be difficult to diagnose clinically and often present late.

Answer 21

Superficial BCC is predominantly present on the trunk and limbs. These are thin plaques or patches bounded by a well-circumscribed, slightly raised, thread-like margin which is irregular in outline and may be deficient at part of the circumference. The epidermis covering the central zone is usually scaly and may demonstrate central clearing or atrophy

Answer 22

Imiquimod stimulates Toll-like receptors 7 and 8 expressed on dendritic cells and monocytes, leading to an increased production of cytokines and chemokines. These in turn promote both Th1 innate and adaptive cell-mediated immune responses which are crucial in the recognition and destruction of the tumour cells

Answer 23

Topical 5% imiquimod cream, applied five times per week over 6 weeks, is effective in clearing 69–100% of superficial BCC and 42–76% of nodular BCC on the trunk and limbs There is a lower response rate in nodular BCC and thicker superficial BCC as well as those in high-risk anatomical sites such as the face

Answer 24

Topical 5-fluorouracil (5-FU) disrupts DNA and RNA synthesis by inhibiting the enzyme thymidylate synthetase. This prevents purine and pyrimidine from becoming incorporated into DNA during the S-phase of the cell cycle When compared with imiquimod in the treatment of superficial BCC, 5-FU cream (5%) has similar efficacy and safety

Answer 25

4 mm clinical margin reported 5-year recurrence rates of 0.7–5% for low risk BCC excision with 4mm margin with 3 mm margins, had 18% of excisions incomplete and a 12.2% recurrence rate. If the BCC was recurrent, standard surgical excision showed 32% incomplete excision with a 13.5%recurrence rate If perineural invasion involving nerves >0.1 mm in diameter is seen, consider postoperative radiotherapy and/or multidisciplinary team (MDT) review

Answer 26

T with a recurrence rate of 4–17% with an average 5-year follow-up

Answer 27

T Hair-bearing areas should be avoided due to potential follicular involvement.

Answer 28

T These mutations result in the unchecked activation of the hedgehog pathway, resulting in unregulated proliferation of basal cells leading to BCC development

Answer 29

T Prolongation of therapy leads to better responses but may require breaks of weeks to months in therapy to reduce side effects without compromising response. Localised recurrences at the edges of the regressed tumour are seen but are able to be effectively treated with standard surgical excision in most cases.

Answer 30

Palmar pits in a patient with naevoid basal cell carcinoma syndrome. The pits are a useful diagnostic feature that occur in about 65% of adults with NBCCS but are relatively rare in children. They are characterised by small, more or less circular pits, which may have a reddish base and are usually 1–2 mm deep The skin manifestations of the syndrome are varied and include BCCs, skin tags, palmoplantar pits, milia, epi- dermoid cysts and lesions that clinically resemble dermal naevi. Affected individuals may develop up to 500 BCCs in their lifetime

Answer 31

Gorlins. Skull X-ray with calcified falx cerebri and a keratocystic odontogenic tumour of the mandible. The keratocystic odontogenic tumours typ- ically occur in the posterior mandible, are usually unilocular, present with radiological lucency and are associated with the crown of an unerupted tooth. Histologically, they show basal cell palisading and hyperplasia. Skeletal abnormalities include spina bifida occulta, bifid or splayed ribs, scoliosis or kyphosis. Less commonly associated anomalies include syndactyly, shortened metacarpals, cleft lip and palate, bicornuate uterus, hypogonadism in males, lymphatic cysts of the mesentery, ocular abnormalities including dystopia canthorum, cataracts and congenital blindness, and a variety of neurological disorders. In addition to BCCs, the syndrome is associated with an increased susceptibility to other neoplasms including rhab- domyosarcoma, ovarian and cardiac fibromas and, in particular, medulloblastoma. Atypical clinical features such as brachydactyly, pulmonary valve stenosis and neurodevelopmental disability should prompt consideration of a contiguous gene deletion syndrome.

Answer 32

diagnostic criteria has been refined to include the need for either two major criteria, one major and two minor criteria, or one major with molecular confirmation

Answer 33

Suspected cases of NBCCS require a full clinical history and exami- nation, imaging including orthopantogram, spinal, chest and skull X-ray, cardiac and pelvic (female) ultrasound and baseline brain magneticresonance imaging. Molecular genetic testing for heritable pathogenic variants of the PTCH1 and SUFU genes can be undertaken with the probability of detection in up to 60% of cases depending on the clinical diagnostic criteria. Genetic testing does not alter the care of individuals meeting the clinical criteria, but may be helpful in the identification and management of their clinically unaffected relatives. Frequent dermatological screening is recommended with radiological screening for medulloblastoma in those under the age of 8 years and with KOT, usually performed annually.

Answer 34

T XLD, only females are affected, Follicular atrophoderma is present at birth or in early childhood, and shows as ‘ice-pick marks’, enlarged follicular ostia on the dorsa of the hands, elbows, feet and face. The follicular changes are not caused by injury or inflammation but there may be facial eczema soon after birth. There may be anhidrosis of the face and head, and hypotrichosis. Milia have been reported as an associated feature. The BCCs appear predominantly on the face typically in the second decade and resemble naevi.Pigmented BCC maybe seen as early as age 5 years

Answer 35

T In the case of facial pigmented AK, slate-grey-to-dark brown dots and globules, annular granular structures and a brown-to-grey pseudo-network can be observed

Answer 36

PDT (conventional) and 5% 5FU

Answer 37

T efficacy superior to imiquimod and PDT

Answer 38

T 5% imiquimod cream has been compared with placebo in a randomised double-blind study, which showed complete clearance rates of 55% and 2.3%, respectively, at 8-week follow-up after one or two cycles of three times per week over 4 weeks of treatment

Answer 39

T (TGA approved)

Answer 40

T The MVK gene maps to chromosome 12q24.11 and DNA sequencing has identified MVK mutations in 33% of familial and 16% of sporadic cases On a background of heterozygous germline mutations in MVK and MVD, it has been demonstrated that a second hit causes somatic homologous recombinations that render the monoallelic mutation biallelic or causes C>T transition mutations in the wild-type allele. As most lesions occur on light-exposed skin, it is likely that this second hit is caused by ultraviolet radiation (UVR).

Answer 41

DSAP usually affects light-exposed sites appearing mainly on the distal extremities. The malar regions and the cheeks may be affected but it is not seen on areas habitually covered by clothes, or on the palms or soles. Patients often notice multiple enlarging rough lesions. These tend to be asymptomatic but may be mildly pruritic, particularly after sun exposure and patients often complain of the lesions being unsightly.

Answer 42

T The rim of DSAP is very much smaller than in Mibelli porokeratosis and never contains a cleft. The onset of Mibelli porokeratosis is often in childhood, and the lesions are usually solitary or few in number and do not necessarily affect exposed parts.

Answer 43

verrucous, nodular, eroded, and pigmented variants

Answer 44

T Long-term arsenic exposure results in impaired immunity characterised by oxidative DNA damage of peripheral polymorphonuclear leu- kocytes and impaired macrophage function in adults with skin lesions

Answer 45

Recommendations for follow-up of high-risk SCC, based on existing evidence, suggest at least a 2-year period with longer follow-up for those on immunosuppression, those with very high-risk disease or multiple tumours

Answer 46

Adjuvant radiotherapy may be an effective therapeutic option in decreasing the risk of tumour progression when a SCC has been excised with close or involved margins, or where completely excised T3 tumours have multiple high-risk features including PNI, depth of >6mm and/or invasion beyond fat

Answer 47

T The process of spontaneous healing usually takes about 3 months.

Answer 48

T Spontaneous regression may occur, which leads to atrophics cars. The mucosal surfaces may be affected as well. Other associated findings include severe pruritus, a Koebner reaction, mask-like facial appearance, ectropion and hoarseness due to nodules on the larynx.

Answer 49

Autosomal dominant inherited condition which is best regarded as a phenotypic variant of the Lynch II cancer family syndrome. It is characterised by the development of one or more sebaceous neoplasms (sebaceous adenoma, sebaceous epithelioma or sebaceous carcinoma) and/or KA along with one or more visceral malignancies. The majority of cases are familial but sporadic cases have been described. most cases present with cutaneous and/or internal tumours after the fifth decade Most patients are disease free until their sec- ond/third decade when cutaneous tumours may start to arise before internal malignancy (22–32% of cases), concomitantly (6–12%) or after internal malignancy has been diagnosed (56–59%). Sebaceous adenomas are found in 25–68% of patients, sebaceous epitheliomas. In 31–86% and sebaceous carcinomas in 66–100% of cases with MTS. In a single report, all 13 patients with MTS, with mutations in MLH1 and MSH2 genes, had Fordyce granules in the oral mucosa, mainly on the vestibular aspect, which may constitute an additional parameter in diagnosing MTS. KA may occur in about 20% of patients with MTS and may be multiple, on light-protected sites and may occur in younger age groups

Answer 50

MTS is caused by germline mutations on one of four DNA mis-match repair (MMR) genes. In about 90% of cases, the mutation occurs in the Mutator S homologue 2 (MSH2) gene which maps to chromosome2p; similar to findings in Lynch syndrome. In fewer than 10% of cases, the mutation is found in the Mutator Lhomolog 1 (MLH1) gene which maps to chromosome 3p. Rarely mutations are found in the Mutator S homolog 6 (MSH6) gene and in post-meiotic segregation increased 2(PMS2) gene MSH6 germline mutations are usually associated with a lower incidence of colon cancer and its later onset but with a higher incidence of extracolonic malignancies, mainly endometrial carcinoma which has an earlier age of onset than colonic carcinoma. BRAF gene mutations can be associated with somatic mutations in the MMR gene and have been found in sebaceous hyperplasia of patients with mutator Y homologue (MYH)-associated polyposis

Answer 51

Most patients develop colorectal carcinoma and nearly 50% have two or more visceral carcinomas. Ten per cent have more than four primary tumours and patients with up to nine tumours have been reported in the literature. Other internal malignancies include carcinoma of the endometrium, stomach, small bowel, genitourinary tract, breast, ovary, pancreas, liver and kidney. There are single reports of an association with non-small cell carcinoma of the lung. Visceral tumours in MTS are usually low-grade malignancies, which tend to permit prolonged survival. The sebaceous carcinomas in this syndrome, like the visceral malignancies, are less aggressive than their counterparts that occur independently. Increased risk of SCC with only mutation status with mainly mutations in MLH1 and MSH2 genes was associated with this risk

Answer 52

Gardner syndrome is a subtype of familial adenomatous polyposis with a higher risk of colon carcinoma and multiple colon polyps. However, patients may also develop sebaceous cysts, epidermoid cysts, fibromas, desmoid tumours and osteomas, not features of MTS.

Answer 53

Patients and their family members should be managed using a mul-tidisciplinary approach, mainly between gastroenterologists and dermatologists, with other specialists becoming involved should tumours arise at other body sites. Although evidence for screening is relatively poor, the general recommendations are for patients to have an annual clinical examination, chest radiography and urine cytology. The frequency of performing colonoscopy varies from once every 3 years to every 1–2 years, particularly in higher risk patients. Female patients require an annual cervical smear and carcinoembryonic antigen testing, along with mammography every 1–2 years up to age 50 and then annually thereafter. Endometrial biopsy has also been recommended every 3–5 years. In one report, two patients presenting with cutaneous signs only were found to have colonic malignancy with PET/CT and further stud- ies are required to assess the reliability of this in detecting occult malignancy. Surgical clearance of internal tumours and sebaceous carcinoma should be performed where possible. For patients with solitary or few cutaneous lesions, surgery in the form of excision or curettage and cautery would be appropriate. For patients with multiple benign cutaneous lesions, isotretinoin has been reported to prevent new tumour development.

Answer 54

Freckle or ephelis The basal cell layer appears hyperpigmented, without alteration of the epidermal architecture melanocortin1 receptor gene (MCR1) has been characterised as the major freckle gene Dermoscopic image showing hyperpigmented lesions with reticular pattern and moth-eaten edge

Answer 55

Peutz Jegher PTEN (phosphate and tensin homologue) Carney Complex LEOPARD (lentigines, electrocardiogram anomalies, ocular anomalies, pulmonary stenosis, abnormal genitalia, retardation of growth and deafness) (all autosomal dominant)

Answer 56

Multiple lentigines in a patient with the Carney complex and a PRKAR1A mutation. Only about a third of patients with the complex have this classic pigmentation. Lentigines (lips, conjunctiva, inner or outer canthi, genital mucosa), primary pigmented nodular adrenal cortical disease (PPNAD), cardiac and skin myxomas, schwannomas, acromegaly, breast and testicular tumours

Answer 57

Compound naevus. (a) Hyperpigmented papule surrounded by symmetrical, lighter brown, macular area. (b) Dermoscopic image showing a structureless brown centre with reticulated periphery

Answer 58

Dermoscopic image of acral naevus showing parallel furrow pattern The most common dermoscopic pattern of acral naevi is the parallel furrow pattern, followed by the lattice-like and fibrillar patterns

Answer 59

Conjunctival. naevi are similar to those occurring in the skin and present as circumscribed, flat or slightly raised macules or papules, occurring most commonly on the bulbar conjunctiva. They are often amelanotic (30% of cases), particularly in children in whom they often acquire pigmentation after puberty. Attachment to the sclera, extension into the cornea and development of ‘feeder’ vessels upon slit lamp examination represent worrisome changes

Answer 60

Combined naevus. (b) Combined naevus with eccentric, structureless, bluish area and peripheral brown, globular pattern

Answer 61

A halo naevus is a melanocytic naevus surrounded by a depig- mentedarea resemblinga halo. Dermoscopic image of a halo naevus showing a symmetrical compound naevus (globular pattern) surrounded by a whitish halo. more commonly seen in children, adolescents and young adults AKA: Synonyms and inclusions * Sutton naevus * Leukoderma acquisitum centrifugum * Perinaevoid vitiligo Halo naevi can be associated with autoimmune disorders like vitiligo, Hashimoto thyroiditis, alopecia areata and atopic eczema. The exact pathophysiology of halo naevi is unknown. They are considered an autoimmune response against naevus cells. There is some laboratory evidence of local and circulating immunological T-cell activation in patients with unexcised halo naevi. Stress and puberty are considered to be triggering factors. Familial cases have been reported. Regression of several melanocytic naevi in patients with metastatic melanoma receiving ipilimumab has been observed. Halo naevi have also been observed in relation with imatinib and tocilizumab treatment. Halo naevi are usually compound melanocytic naevi, although junctional or dermal naevi are occasionally noted. At the time of the halo appearing, they demonstrate a heavy, lichenoid, lymphocytic infiltrate within the dermis, with naevus cells arranged in nests or singly among the inflammatory cells. Initially, a rim of depigmentation appears around a pre-existing melanocytic naevus. This white halo is particularly visible during the summer months when the unaffected adjacent skin acquires a tan. During the following months the naevus may gradually shrink or even disappear completely, leaving a white macule. Approximately half of halo naevi undergo total clinical and histological regression. Halo naevi are located primarily in the back. Multiple halo naevi may develop, while other adjacent naevi remain unchanged. Differential diagnosis In older patients presenting a single lesion, the possibility of a melanoma in regression should be excluded. In a case of melanoma, both the central pigmented area and the surrounding halo appear irregular, while the centre of the lesion presents dermoscopic features that are suggestive of melanoma. In suspicious cases, excisional biopsy should be performed. The depigmented area usually persists for a decade or longer. Management: No treatment is required. Patients should be reassured, particularly in case of multiple lesions, and UV protection measures to avoid sunburn of the depigmented skin area is advised. A halo naevus presenting in an older patient should raise concern, especially in the absence of vitiligo and no history of halo naevi in the past. In such cases, a thorough skin and lymph node examination is recommended to exclude melanoma elsewhere.

Answer 62

This is a melanocytic naevus that develops an eczematous-like inflammatory reaction. It usually presents in young individuals. Meyerson naevi have been associated with atopic eczema. Treatment with interferon α has been reported prior to the development of Meyerson naevi. Histology reveals a common, usually compound, melanocytic naevus with associated spongiotic dermatitis of the overlying epidermis. Also seen is a dense, perivascular infiltrate in the upper dermis composed mainly of CD4+ lymphocytes and occasionally eosinophils. Severe sunburn has been implicated. Presents as a melanocytic naevus that develops a red-coloured halo with overlying scales. The lesion resembles a naevus with superimposed discoid eczema and it may be slightly pruritic. It usually arises on the trunk and proximal extremities. Multiple lesions can occur. Halo dermatitis has been reported around various benign skin lesions (e.g. common acquired and congenital naevi, Sutton naevi, Spitz naevi, clinically atypical naevi, sebaceous naevus, keloids, insect bites, seborrhoeic keratoses, dermatofibromas) and malignant skin lesions (e.g. melanoma, basal and squamous cell carcinomas). In multiple Meyerson naevi, the differential diagnosis includes pityriasis rosea and roseola of secondary syphilis. The eczematoid changes usually resolve spontaneously after a few months, leaving the involved naevus intact, although some degree of hypopigmentation or even complete resolution of the naevus has been described. Meyerson naevus is a similar lesion to halo naevus and may coexist with this entity in the same patient. Occasionally, a Meyerson naevus can progress to a halo naevus or vice versa. Dermoscopy reveals the benign pattern of the involved melanocytic naevus, often blurred by a yellowish, overlying, superficial serocrust. Normally, the eczematous reaction subsides after 1–2 weeks of treatment with a moderately potent topical steroid. Clinical re-evaluation and dermoscopic examination will confirm that the underlying naevus is benign.

Answer 63

Cockade naevus. Dermoscropic image of a cockade naevus showing a darker, central homogeneous pattern, a lighter inner ring and a peripheral brown reticular ring. A cockade naevus is a benign melanocytic lesion with a target-like appearance resembling a rosette. Synonyms and inclusions * Target-like naevus * Kokarden naevus * Naevus en cocarde Usually presents in children and adolescents. It has been proposed that naevus cells in the central and peripheral areas produce melanin more actively, or that there is a lack of melanin synthesis involving the melanocytes of the non-pigmented rim. The central component of the naevus is that of a junctional or compound type, while the periphery of the lesion is composed of junctional nests and may present increased pigment in the dermis. The central component of the naevus is a dark, often papular area, which is surrounded by a non-pigmented circular zone and an outer pigmented ring. Lesions are usually multiple and located on the trunk, or on the scalp in young patients. A target-like appearance has also been reported in association with blue naevi and melanoma. Dermoscopy reveals a naevus with a darker, central globular or homogeneous pattern, surrounded by a structureless inner ring and a more peripheral darker reticular ring A cockade naevus is a benign lesion, thus no treatment is required.

Answer 64

A targetoid haemosiderotic naevus derives from mechanical trauma of a melanocytic naevus, which is usually elevated or exophytic. It is common in children and young adults. The upper chest is the most common location. Targetoid haemosiderotic naevus. (a) Naevus acutely presenting with a haemorrhagic halo. (b) Dermoscopic image showing a peripheral, structureless, purple rim around a central pre-existing naevus. Histopathologically, targetoid haemosiderotic naevus consists of naevus cells mingled with extravasated blood vessels and an increased number of irregular, ectatic, vascular channels. The peripheral halo demonstrates extensive haemorrhage with haemosiderin and fibrin deposits combined with slit-shaped vascular channels that dissect in between collagen bundles. A mild, inflammatory,primarily eosinophilic infiltrate is also seen. Targetoid haemosiderotic naevus usually appears as a sudden change of pigmentation in a pre-existing naevus following mechanical irritation, usually from clothing, shaving or scratching. A history of trauma or irritation is not always apparent to the patient. Symptoms indicating trauma such as pain, tenderness or pruritus are common. Clinically, the lesion presents as a brown, red-brown or violaceous papule surrounded by a thin pale area and a peripheral ecchymotic area that tends to expand, become fainter and resolve while the central papule persists. The differential diagnosis includes targetoid haemosiderotic haemangioma, cockade naevus, traumatised angiokeratoma and melanoma. Investigations Dermoscopy reveals haemorrhagic changes with a red to purple colour, surrounding a naevus with a usually globular pattern. Jet-black areas with irregular shape and size as well as comma-shaped vessels are also seen. The periphery of the lesion representing the ecchymotic halo shows an ill-defined, pale area surrounded by a reddish zone with jagged edges. Management Management includes reassurance of the patient and the use of a topical antibiotic or steroid preparation until the inflammatory/ haemorrhagic changes have resolved.

Answer 65

A Spitz naevus is a melanocytic lesion characterised by spindled and/or epitheloid naevomelanocytes. Spitz naevi are more commonly seen in younger ages. Approximately 40% of lesions occur in patients under the age of 15 years and 77% before the age of 30. Disseminated,eruptive Spitz naevi have been reported to occur with Addison disease, HIV infection, chemotherapy, puberty and pregnancy. Most lesions area cquired, but up to 7% of Spitz naevi can occur congenitally. The ‘classic’ Spitz naevus typically is asymmetrical and well-defined compound naevus. Naevomelanocytic nests are neatly located between keratinocytes, unlike their disorderly arrangement in melanoma. The naevo melanocytic nests at the dermal–epidermal junction are often separated from the surrounding keratinocytes by a cleft caused by a retraction artefact. The naevus cells may be either spindle shaped, streaming into the dermis in interlacing bundles, or epithelioid, arranged in clusters, with giant and multinucleated naevus cells seen among them. Kamino bodies (i.e. amorphous eosinophilic globules containing periodic acid–Schiff-positive basement membrane constituents) are noted intraepidermally and at the dermal–epidermal junction. Their presence is neither sensitive nor specific for Spitz naevi as they may also be present in early melanoma. In classic Spitz naevi, dermal naevomelanocytic nests and fascicles exhibit a zonation phenomenon with depth, for example uni- formity in size, shape and spacing along horizontal planes. Immunohistochemistry can be used to differentiate Spitz naevi from melanoma. MIB1, which stains the proliferative marker Ki-67, has a lower expression in Spitz naevi compared with melanoma, while HMB-45 is more superficially expressed with diminished staining in the deeper dermal component. S100 and Mart-1 are more weakly stained in Spitz naevi, whereas the S100A6 subtype shows more intense and diffuse expression in Spitz naevi compared with its weak and patchy staining in melanoma. p16 reactivity is stained more intensely in desmoplastic Spitz naevi, while it is largely absent in melanomas. The very rare incidence of NRAS and BRAF mutations in Spitz naevi compared with other melanocytic lesions, and the presence of HRAS mutations in a subgroup of Spitz naevi (c. 20%), suggests a distinct activation of the RAS pathway components in different melanocytic neoplasms. The majority (c. 55%) of Spitz naevi and atypical Spitz tumours have mutually exclusive kinase fusions as primary initiating genomic events. Genomic rearrangements activate oncogenic signalling pathways and involve the kinases ALK, ROS1, NTRK1, NTRK3, BRAF, RET and MET

Answer 66

Cellular blue naevus. Dermoscopic image of a cellular blue naevus showing a well-circumscribed, protuberant nodule with homogeneous dark blue pigmentation and randomly distributed whitish zones corresponding histopathologically to fibrosis.

Answer 67

Blue naevus. (b) Dermoscopic image of a blue naevus showing a homogeneous blue pattern.

Answer 68

T the relative risk for melanoma is even greater, reaching 85-fold in melanoma-prone family members with dysplastic naevi

Answer 69

Monilethrix on the nape of the neck showing follicular keratoses and short, broken hairs. The hair shaft is beaded and breaks easily, particularly at sites of friction. Broken hair may be accompanied by follicular keratosis, most commonly on the nape and occiput

Answer 70

Pili torti Affected hairs are brittle and may break off, particularly in areas subject to trauma, such as the occiput. Affected hairs have a spangled appearance in reflected light. Non-scalp areas (e.g. eyebrows/eyelashes) may also be affected. Rotations of the hair shaft run in groups of three to five twists before the shaft normalises. Assessment of hearing loss, serum copper/ceruloplasmin levels and/or nutritional deficiencies should be done depending on the clinical presentation

Answer 71

Trichorrhexis invaginata The hair in Netherton syndrome is short, dry, lustreless and fragile. The eyebrows and eyelashes are sparse or absent. Unfortunately, the diagnostic hair changes of trichorrhexis invaginata can vary over time and location. Therefore, it is important that samples of at least 100 hairs are carefully examined by light microscopy on several occasions before a definite negative is asserted. Alternatively, finding a single trichorrhexis invaginata node in a single hair is a conclusive positive. Consider sampling eyebrows hairs as this is shown to increase the likelihood of successful diagnosis. Unfortunately, the diagnostic hair changes of trichorrhexis invaginata can vary over time and location. Therefore, it is important that samples of at least 100 hairs are carefully examined by light microscopy on several occasions before a definite negative is asserted. Alternatively, finding a single trichorrhexis invaginata node in a single hair is a conclusive positive

Answer 72

Pili annulati is often diagnosed coincidentally due torecognition of the unusual shiny, spangled appearance of the hair. The light bands identified by eye represent the air-filled cavities that are more easily seen in lighter hair colours.

Answer 73

Uncombable hair Pili triangulati et canaliculi Hair is normal in quantity and sometimes also in length, but the wild, disorderly appearance totally resists all efforts to control it with a brush or comb. The hair is often a silvery blond colour. The eye brows and eyelashes are normal. The hairs are triangular or kidney-shaped in cross-section and longitudinal grooving is identified. Recently, techniques to identify the hairs in cross-section using epoxy resin or frozen sectioning have been described. Samples should show >50% abnormal hairs to make the diagnosis.

Answer 74

Typically, loose anagen syndrome is seen in fair-haired children, aged 2–9 years and mostly girls. The hair is slightly unruly, of uneven length and patchy in quality, with a history of not growing properly and never needing cutting. Hair is usually easily and painlessly plucked from the scalp. Diagnosis is suggested when 3–10 anagen hairs are easily removed using the hair pull test, although caution is required as the numbers of hairs removed can vary over time, so a single negative hair pull does not exclude the diagnosis. Diagnosis can be confirmed by trichogram and requires at least 70% of hairs to be loose anagen hairs. Microscopy of loose anagen hairs shows ruffling of the cuticle adjacent to the anagen bulb, giving the appearance of a ‘floppysock’, along with the absence of an attached root sheath (helping to differentiate these hairs from normal plucked anagen hairs). 61% of normal children under 10 years have some degree of loose anagen hairs on hair pull, although the numbers of hairs removed were small (one or two loose anagen hairs per pull) compared with significantly higher numbers seen in loose anagen syndrome. This may reflect immature anchoring and higher anagen levels in this younger age group.

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