Keratoacanthoma

Keratoacanthoma

Definition

Keratoacanthoma is a common, rapidly growing squamoproliferative tumour that may spontaneously regress. It is histologically indistinguishable from (and likely a variant of) well-differentiated cutaneous invasive squamous cell carcinoma, with distinct clinical behavior.

Synonyms

Welt-differentiated squamous cell carcinoma, keratoacanthoma type; keratoacanthoma-like squamous cell carcinoma

Epidemiology

Keratoacanthomas typically arise in the sun-exposed skin of older, fair-skinned individuals between the sixth and seventh decades of life and have a slight predilection for men. Rare cases occur in childhood and adolescence in association with organoid naevus or xeroderma pigmentosum.

Etiology

Ultraviolet (UV) radiation, photon radiation, trauma (e.g. at sites of a skin graft or vaccination), infections, and chemical carcinogens have been linked to the development of keratoacanthoma lesions, with solar damage being the predominant risk factor. Other factors include immunosuppression/immunodeficiency, tattoos, and BRAF inhibitors. Human polyomavirus 6 (HPyV6) DNA was recently detected in keratoacanthomas, and other serotypes (HPyV19 and HPyV48) have been isolated in giant keratoacanthomas and keratoacanthomas in HIV-infected patients.

Localization

Keratoacanthomas most commonly occur in facial skin (in as many as 70% of cases in temperate climates); they also commonly occur on the dorsum of the hands and forearms among men and on the legs among women.

Clinical features

Solitary keratoacanthoma

This is the most common variant. It presents as a symmetrical, dome-shaped tumour, capped with keratin. It evolves rapidly and may involute over the course of several months. The size ranges from a few millimeters to 20 cm. Giant keratoacanthomas (>5 cm) have a predilection for the nose and the dorsum of the hands; they can reach up to 15 cm, with destruction of underlying tissues. Three clinical stages have been observed: a proliferative stage (a rapidly enlarging erythematous papule or nodule with a smooth surface), a mature stage (a central whitish-yellow nodule with a crateriform keratotic core), and a regressing stage (a keratotic nodule that progressively flattens in association with elimination of the central keratotic plug, sometimes followed by the formation of a hypopigmented scar).

Multiple keratoacanthomas

These rare tumours can be sporadic or familial. Sporadic multiple keratoacanthomas may be associated with prurigo nodularis, usually on the sun-damaged lower legs of elderly women.

Multiple familial keratoacanthomas of Ferguson-Smith type

These keratoacanthomas, also known as multiple self-healing squamous epithelioma, were first described in Scottish families with an autosomal dominant inheritance pattern with variable penetrance. Patients may have hundreds of keratoacanthomas, each with characteristics similar to those seen in solitary keratoacanthoma.

Multiple keratoacanthoma centrifugum marginatum

Theses rare skin tumours show persistent growth with an annular, coral reef— like appearance. The lesions involve the back of the hands and can become very large, approaching 20 cm.

Generalized eruptive keratoacanthomas of Grzybowski

Affected patients have a generalized eruption of hundreds to thousands of small, well-demarcated papules (some with keratotic centres), predominantly in unexposed skin. The condition is exceedingly rare, and familial clustering has been described.

Subungual keratoacanthoma

This rapidly growing and locally destructive tumour originates in the distal nail bed, separating it from the nail plate. The thumb, middle finger, and big toe are most commonly involved.

Histogenesis

Most examples of keratoacanthoma affect hair-bearing skin, and are most likely to be derived from follicular infundibular/isthmus keratinocytes. Rare tumours located on glabrous skin and mucous membranes are probably derived from epithelial keratinocytes.

Genetic profile

The MAP3K8 (TPL2) oncogene may be a driver common to the development of both keratoacanthoma and squamous cell carcinoma. Patients with multiple familial keratoacanthomas of Ferguson-Smith type have DNA repair failures associated with Muir—Torre syndrome and xeroderma pigmentosum. Disease-specific mutations in TGFBRI have also been identified in patients with multiple familial keratoacanthomas of Ferguson-Smith type. There is a possible role of TP53in the development of some keratoacanthomas; mutant p53 oncoproteins are found in about 10% of tested lesions.

Genetic susceptibility

Rarely, there is a genetic predisposition to developing keratoacanthomas, in particular multiple familial keratoacanthomas of Ferguson-Smith type. Muir—Torre syndrome is commonly associated with keratoacanthoma lesions, suggesting that the genetic defect (or defects) that causes the syndrome also plays an etiological role in keratoacanthoma.

Prognosis and predictive factors

Many (if not most) keratoacanthomas eventually undergo resolution, but central facial giant keratoacanthoma and subungual keratoacanthoma may be locally aggressive. It is impossible to predict with certainty the behaviour of a well differentiated squamoproliferative lesion on the basis of a partial biopsy, or when margins are involved.

Reference:

WHO classification of skin tumours, 4th edition (2018): 36-38.

Melanocytic Naevus

Junctional, compound, and dermal naevi

Definition

Junctional, compound, and dermal naevi are benign localized neoplastic proliferations of naevus cells (a type of melanocyte). Like all melanocytic naevi, these lesions are defined by the presence of nests of melanocytes.

Synonyms

Common acquired naevi; banal naevi

Epidemiology

Acquired naevi appear during childhood and reach maximum number in adolescence, declining in number thereafter in cross-sectional studies. This finding may be due to a cohort effect, a process of senescence and disappearance over time, or both.

Etiology

The prevalence of naevi in various populations depends on phenotypic factors (in particular sun susceptibility), sun exposure patterns, and genetic susceptibility, resulting in mutations of a single oncogene in a single cell, which expands to form a clone.

Localization

Naevi are widely distributed over the body, with the most frequent site being

the trunk.

Clinical features

These are localized, generally symmetrical and uniformly pigmented lesions, typically <5 mm in diameter They have been assumed to evolve from initial junctional proliferations to compound and then dermal naevi with accompanying development of a papular component, loss of the junctional component, and loss of pigment; however, a more complex model of separate evolution has been proposed.

Histogenesis

These lesions are thought to evolve as junctional proliferations of melanocytes, related to the mutation of a single oncogene as a driver mutation in actinically altered skin {2390}, and to evolve through the stages of compound and dermal naevi as described above.

Genetic profile

Most acquired naevi have activating mutations of the oncogene BRAF (typically BRAF p.V600E) and less often mutations of NRAS. Different mutations are associated with distinct forms of naevi of other types, discussed in the respective sections. BAPI-inactivated melanocytic lesions must be distinguished from Spitz naevi and atypical Spitz tumours, and are more akin to naevi with partial transformation by a second genomic event (i.e. BAPI loss).They usually lack epidermal hyperplasia, are usually epithelioid rather than spindled, often include a second naevus cell component, lack BAPI expression, and are usually BRAF-mutant.

Genetic susceptibility

Several so-called naevus susceptibility genes have been described, but this information has not yet been translated into clinical practice. Prognosis and predictive factors Naevi have medical significance in relation to melanoma, as simulants, potential precursors, and risk markers (discussed in the sections on dysplastic naevi and melanomas). Briefly, individuals with an increased total number of naevi or an increased number of large naevi are at increased risk of melanoma as deter-mined in case—control and prospective cohort studies. It has been shown that about one third of melanomas arise in compound naevi. Although many melanomas are associated with precursor naevi, the risk of progression for individual lesions is very low.

Reference:

WHO classification of skin tumours, 4th edition (2018): 80-81.

Lichenoid keratosis

Solar Keratosis (Actinic Keratosis)

Dermatofibroma

Dermatofibroma (fibrous histiocytoma) and variants

Definition

Dermatofibroma (fibrous histiocytoma) is a common benign papular or nodular skin lesion composed of variable combinations of fibroblastic cells, macrophages, and coarse collagen.

ICD-O code

Dermatofibroma (fibrous histiocytoma)   8832/0

Synonyms

Benign fibrous histiocytoma; histiocytoma (cutis); fibroma durum; subepidermal nodular fibrosis orsclerosis; sclerosing haemangioma.

Epidemiology

Dermatofibroma can arise at any age, but is most common in the third and fourth decades of life. The classic type is more common in younger females, particularly on the legs. Other variants have a more equal sex distribution.

Etiology

It has been debated whether dermatofibroma is inflammatory or neoplastic. Some lesions have shown clonality and recurrent translocations suggesting neoplasia. This entity has also been reported to arise after trauma, insect bites, or folliculitis, suggesting an inflammatory origin. More recently, gene fusions involving PRKC Band PRKCD (encoding protein kinase Cisoforms) have been noted in a subset of cases, confirming a neoplastic nature.

Localization

The lesions are most commonly seen on the legs, followed by the arms and trunk. Occasional lesions are seen on the hands, feet, and head and neck. The cellular variant is the subtype most commonly involving the head and neck.

Clinical features

Most dermatofibromas asymptomatic papules are that isolated evolve rapidly and then stabilize. Early stage lesions are typically erythematous, but older ones are brown or skin-toned, often with a peripheral brown rim. The lesions are typically 1 cm in diameter but are occasionally up to 10 cm. They are typically firm, well circumscribed, and symmetrical. Most lesions are raised and dome-shaped and show a central dimple when squeezed. They may be cystic, eroded, or crusted. Occasionally several lesions are present, and rarely there can be dozens, either widely distributed or agminated. Multiple lesions may have no clinical significance, but they have been reported in conditions associated with immunosuppression and in association with immunosuppressive drugs.

Histogenesis

There is evidence of fibroblastic, myofibroblastic, and/or macrophage differentiation.

Prognosis and predictive factors

Dermatofibroma is a benign lesion. Incomplete excision may result in local non-destructive recurrence. There is conflicting evidence as to whether dermatofibroma of the face behaves more aggressively than dermatofibroma at other anatomical sites. The risk of local recurrence is higher with the cellular, atypical, and aneurysmal sub-types. Extraordinarily rare lesions have metastasized to lymph nodes and/or lung; most have been of the cellular, atypical, or aneurysmal subtype. There is some evidence suggesting that metastasizing tumours have more chromosomal aberrations than are typical of standard indolent dermatofibroma.

Reference:

WHO classification of skin tumours, 4th edition (2018): 310-312.

Squamous cell carcinoma (SCC)

Squamous cell carcinoma

Definition

Cutaneous squamous cell carcinoma (SCC) is a malignancy of epidermal keratinocytes that exhibits various degrees of differentiation that partially recapitulate the cytology of squamous cells of the epidermal stratum spinosum. The lesions can be in situ or invasive with the potential for metastasis.

ICD-O code

Squamous cell carcinoma NOS 8070/3

Epidemiology

The incidence of SCC is difficult to estab-1ish, but data on non-melanoma skin cancer suggest that there were an estimated701 000 SCC tumours affecting 430 500people in the USA in 2006 (assuming that of tumours are SCC). SCC is the second most common form of skin cancer (after basal cell carcinoma) and is more common in men than in women. Most cases occur in sun-exposed skin of elderly individuals, most commonly individuals with lighter skin pigmentation.

Etiology

In addition to ultraviolet (UV) radiation, other factors that have been implicated in the etiology of SCC include chronic immunosuppression, other forms of radiation, topical carcinogens, burn scars, chronic inflammation, sinus tracts, HPV infection, arsenic, and coal tar. Cutaneous SCC was the first occupational cancer to be identified, described in the scrotal skin of British chimney sweeps in1775 by Percivall Pott.

Localisation

The sites most often affected are chronically sun-exposed areas, including the face and lips, ears, balding scalp, arms, trunk, and (particularly in women) legs. More widespread sites may be affected in those who have used indoor tanning. In rare lesions associated with HPV infection or immunosuppression, the genitalia and distal digits (particularly the subungual region) are commonly involved.

Clinical features

SCC in situ may appear as roughened hyperkeratotic lesions mimicking benign keratoses, dermatoses (e.g. psoriasis), or lichen simplex chronicus. With invasion and progressive growth, hyperkeratotic nodules may develop ulceration. The well differentiated keratoacanthoma variant of SCC forms crateriform lesions with central keratin plugs. Less well differentiated tumours produce irregular, erythematous scaling nodules and plaques. Lesions with perineural spread may produce pain or paraesthesias. Lymph node spread is the primary route of metastasis. When visceral lesions develop, they most commonly affect the lung, followed by the bone, CNS, and liver.

Histogenesis

Most UV radiation—related cutaneous SCCs appear to develop through a multistep process in actinic keratoses or infields of squamous dysplasia. Common mutations involve tumour suppressor genes such as TP53, NOTCHI, and NOTCH2 {1800). Activating mutations in genes such as HRAS and KRAS are also frequently involved. UV radiation—induced TP53 mutations likely occur early on in the process. Advanced age, immunosuppression, and environmentally determined defects in the epigenome appear to contribute to impaired elimination of precursors of malignant transformation. Cutaneous SCC probably arises from an epidermal or follicular stem cell.

Genetic profile

Recent genetic expression profile studies suggest that the differentially expressed genes CXCL8 (IL-8), MMPI, HIFIA,ITGA6, and ITGA2 are promising diagnostic and therapeutic targets .

Genetic susceptibility

Patients with xeroderma pigmentosum, vitiligo, and albinism are at increased risk of SCC. A recent two-stage genome-wide association study of a large number of SCCs revealed 11 susceptibility loci. Of these, 7 are related to pigmentation: MCIR, AS/R TYR, SLC45A2 OCA2,IRF4, and BNC2. The other 4 are involved in tumour immune evasion, apoptosis inhibition, or other oncogenic pathways:liq23.3 (CADMI), 2p22.3, 7p21.1 (AHR),and 9q34.3 (SEC16A).

Prognosis and predictive factors

Confirmed high-risk prognostic features are tumour thickness > 2 mm, Clark level IV or V invasion, perineural invasion, primary site on the ear or lip, and poor differentiation. Perineural invasion of nerves >0.1 mm in diameter correlates with higher disease-specific death rates.

Acantholytic squamous cell carcinoma

Definition

Acantholytic squamous cell carcinoma (SCC) is a histological variant of invasive SCC characterized by impaired intercellular adhesion that may result in the formation of pseudo glandular spaces.

ICD-O code

8075/3

Synonyms

Adenoid squamous cell carcinoma; pseudo glandular squamous cell carcinoma

Epidemiology

The acantholytic variant accounts for< 5% of all SCCs, although the criteria for this designation (focal versus wide-spread acantholysis) are not well established. Older male patients are most frequently affected, and an increased incidence has been reported in organ transplant recipients.

Etiology

Given that most acantholytic SCCs occur in chronically sun-exposed sites, ultra-violet (UV) radiation—induced damage is likely a causative factor. The known association with chronic immunosuppression implies a role for defective immunosurveillance.

Localisation

The lesions often involve skin of the head, neck, face, and ears. Other sun-exposed sites can also be involved. In one review, about 60% of lesions involved the head and neck, and 40% involved the trunk and extremities .

Clinical features

The clinical appearance of acantholytic invasive SCC is the same as that of its non acantholytic counterpart (SCC-NOS).

Histogenesis

The histogenetic factors are most often the same genomic, molecular, and causative factors that are applicable to ordinary invasive SCC. Compared with non-acantholytic SCCs, the acantholytic variant has been shown to have decreased expression of desmoglein 3 and E-cadherin. Defective desmosomal protein expression has been confirmed and is probably largely responsible for the acantholytic pattern observed histologically. The genetic pro-file of and potential susceptibility loci for acantholytic SCC are not yet understood.

Prognosis and predictive factors

It has been suggested that acantholytic SCC is a more aggressive variant of SCC , with a mortality rate at follow-up of 19%, although more-recent data conflict with this interpretation. Histological attributes that may confer aggressive behaviour have recently been comparatively evaluated for acantholytic versus non-acantholytic SCC; these included microscopic tumour diameter, depth of invasion, degree of differentiation, and presence of perineural invasion. No significant differences between acantholytic and non-acantholytic ordinary SCCs were identified; overall, the notion that acantholytic SCC is a biologically and clinically more aggressive variant of SCC has not been substantiated.

Spindle cell squamous cell carcinoma

Definition

Spindle ceil squamous cell carcinoma (SCC) is a rare, poorly differentiated variant of SCC; it is composed predominantly of spindled tumour cells with partial or complete loss of morphological squamous differentiation.

ICD-O code

8074/3

Synonyms

Pseudosarcomatous squamous cell carcinoma; sarcomatoid squamous cell carcinoma

Epidemiology

These skin tumours arise most commonly in elderly White men, and rarely in Asian populations. The incidence is highest among individuals aged > 70 years. The reported age range for penile tumours is broad (28—81 years).

Etiology

Ultraviolet (UV) radiation exposure, iatrogenic ionizing irradiation, scarring burns, solid-organ transplantation, and immunosuppression predispose individuals to this variant. Penile tumours are frequently associated with high- or low-grade squamous intraepithelial dysplasia or lichen sclerosus.

Localisation

Spindle cell SCC typically arises in the sun-exposed skin of the face and head, neck, chest, and upper extremities. Simi-lar tumours are found in mucocutaneous regions of the head and neck (e.g. the larynx, hypopharynx, oropharynx, and nasal cavity), as well as within the urogenital tract, and are well described on the distal penis (e.g. the glans/pre-puce and foreskin).

Clinical features

Spindle cell SCC is typically a raised orexophytic plaque, nodule, or tumour, and is indistinguishable from classic SCC. It is often about 2 cm in largest dimension, and can reach up to 10 cm. Patients often present with bleeding or ulceration, and may report a history of rapid tumour growth.

Histogenesis

A monoclonal origin for these tumours is the currently accepted theory. Themorphological changes have been postulated to be caused by epithelial—mesenchymal transition, in which the precursor squamous cells lose polarity and cohesiveness and transform into spindle-shaped cells, acquiring increased motility and invasiveness.

Prognosis and predictive factors

Spindle cell morphology itself may be a predictor of poor prognosis. Depth of invasion (particularly invasion into bone or muscle), as well as origination at the site of a burn or radiation damage (including sun damage) may be associated with worse outcome or death. Positive margins are associated with significantly higher rates of recurrence and metastasis, and with significantly poorer survival. Penile variants have a high rate of metastasis and are associated with a high rate of death due to metastatic dis-ease.

Verrucous squamous cell carcinoma

Definition

Verrucous squamous cell carcinoma (SCC) is a rare, well-differentiated variant of cutaneous SCC; it has a characteristically undulant architecture and often exhibits locally aggressive behaviour, yet has low potential for metastasis. Similar lesions also affect mucosal surfaces.

ICD-O code

8051/3

Synonyms

Oral florid papillomatosis; Ackerman tumour {338,488}; epithelioma cuniculatum; Buschke—Löwenstein tumour; giant condyloma acuminatum; papillomatosis cutis carcinoides

Epidemiology

Verrucous SCC is predominantly a tumour of older men, with 75% of patients aged 2 60 years.

Etiology

Chronic irritation, inflammation, HPV infection, and impaired immunity have been proposed as possible etiological factors. As with other forms of cutaneous SCC, chemical carcinogens and environmental exposures have also been implicated. However, the precise inciting factors responsible for this uncommon variant remain unknown.

Localisation

Verrucous SCC can affect both oral mucosa and skin. The mucosal site of predilection is the oral cavity (Ackermantumour); cutaneous lesions most often involve the palms, soles (epithelioma cuniculatum), distal digits, and genital region (Buschke—Löwenstein tumour), but isolated reports indicate that verrucous SCC can arise at virtually any cutaneous site, including the skin of the scalp, face, back, and extremities, some-times in association with chronic ulcers and scars, such as in the pretibial variant (papillomatosis cutis carcinoides).

Clinical features

The clinical appearance of cutaneous verrucous SCC varies according to its site of occurrence. Palmoplantar lesions tend to grow and evolve slowly, forming hyper-keratotic plaques that may be confused with verrucae or callosities. Anogenital lesions form exophytic, condylomatoid excrescences that may be deeply invasive and difficult to eradicate, particularly in the setting of immunocompromise. Occasionally, tumours can have a more nodular clinical appearance.

Histogenesis

Verrucous SCC has been described in association with a variety of reactive and inflammatory conditions, including vulvar lichen planus, although the precise histogenesis remains unclear. The role of HPV is controversial, in part because of diagnostic confusion between condylomatous and hyperplastic lesions and true verrucous SCC. An analysis of13 rigorously defined verrucous SCCs from head and neck, anogenital, and extragenital skin using PCR-based HPV detection failed to implicate a causal role for HPV. However, there is a clear association between certain oncogenic HPV types and cutaneous SCC, particularly in the setting of immunosuppression, and the potential role of HPV in verrucous SCC warrants further investigation.

Genetic profile

Overexpression of MDM2, a negative regulator of p53, has been implicated.

Prognosis and predictive factors

Incompletely excised lesions have a high recurrence rate, and recurrences can be more aggressive than the initial tumour. Metastasis generally does not occur, although transformation to more-aggressive forms of SCC has been described inpatients who had received irradiation or chemotherapy.

Adenosquamous carcinoma

Definition

Adenosquamous carcinoma is a rare squamous cell carcinoma (SCC) variant that exhibits mixed squamous and glandular differentiation and aggressive clinical behaviour.

ICD-O code

8560/3

Etiology

Although this is considered to be a variant of SCC with divergent glandular differentiation, the pathogenesis is unknown. Malignant transformation from epithelial stem cells differentiating into both squamous and glandular-like cells is a plausible explanation.

Clinical features

These tumours occur mostly in the head and neck of elderly patients, most frequently in men. Clinically, they can be indistinguishable from typical SCC, presenting as an indurated keratotic plaque. The incidence is likely higher among immunosuppressed patients.

Prognosis and predictive factors

This variant has been associated with an aggressive clinical course, with a high rate of recurrence and metastasis. Because of the relative frequency of nerve involvement and subclinical extension, meticulous examination of all resection margins to assess the adequacy of excision is required.

Clear cell squamous cell carcinoma

Definition

Clear cell squamous cell carcinoma (SCC) is a histological variant of SCC that microscopically shows abundant clear cytoplasm. There is no consensus on the required proportion of clear cells for the definition of clear cell SCC, but > 25%has been suggested. The tumours may be invasive or in situ.

ICD-O code

8084/3

Epidemiology

This rare SCC variant often occurs on sun-damaged skin of older men.

Etiology

The risk factors appear to be similar to those for conventional SCC.

Localisation

The head and neck are affected most frequently. Similar tumours on the glans penis may behave aggressively.

Clinical features

These tumours, which often present in elderly men, have no clinical features to distinguish them from conventional SCC. The presence of ducts, highlighted by staining for CEA and EMA (epithelial membrane antigen), helps to identify porocarcinoma, hidradenocarcinoma, and dermal duct tumours. In clear cell cytokeratin fibroxanthoma, atypical staining is negative and keratinization is absent {1899}. Clear cell and balloon cell melanomas stain for melanocyte markers. If there is no evidence of epidermal origin, metastatic carcinomas should be considered, especially from the kidney (PAX8-positive).

Genetic susceptibility

The genetic susceptibilities are unknown beyond those associated with conventional SCC.

Prognosis and predictive factors

The prognosis of clear cell SCC is comparable to that of other SCC types.

Other (uncommon) variants

Definition

The other variants of cutaneous squamous cell carcinoma (SCC) are a poorly defined group of uncommon tumours that exhibit differentiation characterisation stromal responses that result in diagnostic ambiguity.

ICD-O codes

Squamous cell carcinoma with sarcomatoid differentiation 8074/3

Lymphoepithelioma-like carcinoma 8082/3

Pseudovascular squamous cell carcinoma 8074/3

Squamous cell carcinoma with osteoclast-like giant cells 8035/3

Synonyms

For SCC with sarcomatoid differentiation: carcinosarcoma; metaplastic carcinoma; pseudosarcomatous squamous cell carcinoma; sarcomatoid squamous cell carcinoma; For pseudovascular SCC: pseudoangiosarcomatous squamous cell carcinoma; pseudovascular adenoidsquamous cell carcinoma;pseudo angiomatous squamous cell carcinoma {1410}

Epidemiology

These SCC variants are exceedingly rare.

Etiology

The etiology is similar to that of common forms of SCC.

Localisation

SCC with sarcomatoid differentiation typically involves sun-exposed skin of the face and head, neck, chest, and upper Lymphoepithelioma-like extremities. Carcinoma (LELC) of the skin typically involves sun-exposed skin, most often of the head and neck. Pseudovascular SCC affects ultraviolet (UV) radiation—damaged skin of the head and scalp, and typically occurs in elderly individuals. SCC with osteoclast-like giant cells(SCC-OGC) generally involves the head and neck of elderly individuals.

Clinical features

These rare variants of SCC typically show rapid growth but have no individually characteristic features.

Histogenesis

The rarity of these uncommon variants precludes definitive data regarding histogenetic pathways. Although LELC of the skin histologically resembles undifferentiated nasopharyngeal carcinoma(lymphoepithelioma), a strong association with EBV has not been demonstrated, which facilitates this variant’s distinction from lymphoepithelioma.

Prognosis and predictive factors

Some pseudo vascular SCCs and SCC OGCs demonstrate more-aggressive biological behaviour than do other SCC variants.

Reference:

WHO classification of skin tumours, 4th edition (2018): 35-45.