Sebaceous Lesions

Question 1

Sebaceous hyperplasia

Answer 1

• Most common sebaceous gland lesion
• Usually elderly patients on nose or cheeks
• Umbilicated yellowish papules

Causes:
* Sun exposure
* Immunosuppressant
* Heart and renal transplant recipents

Micro:
* Expansion of normal lobular sebaceous gland architecture
* Without thickening of peripheral germinative layer of seboblasts

Question 2

Sebaceous adenoma

Answer 2

• Benign neoplasm composed of mature sebaceous lobules with the expansion of germinative basaloid cell layers at the periphery
• Well circumscribed, multilobulated tumor
• Increased number of basaloid germinative cells of more than 2 layers
• Shows distinct maturation, meaning that the basaloid germinative cells are usually at the periphery and the sebaceous cells are located centrally
• Associated with Muir-Torre syndrome, a variant of Lynch syndrome with mutations in the DNA mismatch repair (MMR) genes
• MTS is caused by germline variants in the DNA mismatch repair (MMR) genes encoding for MSH2 and MLH1, accounting for most of the cases

Micro:
* Well circumscribed, nodular growth of lobules consist of admixture of basaloid cells and mature sebocytes
* Some lobules may communicate directly with the surface epithelium
* Basaloid cells are usually located at the periphery of lobules and sebaceous cells with intracytoplasmic lipid vacuoles, which are usually located at the center of lobules
* Basaloid cells are composed of expanded germinative layer, with more than the normal 2 cell layers seen in mature sebaceous glands or sebaceous hyperplasia but still less than 50% of the tumor volume (> 50% is seen in sebaceoma / sebaceous epithelioma)
* Increased mitotic activity is sometimes seen in the basaloid cell componen

Question 3

Sebaceoma

Answer 3

• Benign sebaceous neoplasm consisting of an admixture of mature sebocytes and predominantly immature basaloid cells (> 50% of the neoplasm)

Micro:
* Dermal based tumor with rare epidermal attachments
* Consists of variably sized, discrete nodules that lack lobular organization architecture
* Cytologically, the sebocytes have multiple cytoplasmic vacuoles and scalloped nuclei
* The immature basaloid component features frequent mitotic activity but lacks atypical forms or necrosis
* Cystic spaces and duct-like structures are often present, displaying an eosinophilic cuticle and occasional holocrine secretions

Molecular:
* Sebaceomas commonly have mutation of RAS family genes (HRAS and KRAS), TP53, CDKN2A, EGFR and CTNNB1 when examined by next generation sequencing
* Abnormalities of TP53 were most frequently found
* * Associated with Muir-Torre syndrome (MTS) but can also be an isolated (sporadic) tumor

Question 4

Sebaceous carcinoma

Answer 4

• Malignant neoplasm with sebaceous differentiation
• Generally classified into periocular and extraocular
• Mostly occurs sporadically in elderly patients with an equal gender distribution; periocular locations have a female predominance
• Most common in periocular area, head and neck

Periocular:
* 1.0 - 3.2% of all malignant eyelid tumors
* Upper eyelid > lower eyelid
* Originates from meibomian glands, Zeiss glands, caruncle or skin of eyebrow

Extraocular:
* Occurs on the head and neck mostly, then rarely on the trunk, extremities, genitalia, external auditory meatus
* Very rarely can occur in extracutaneous sites, such as lungs, salivary glands and breast
* Can rarely occur in a nevus sebaceus of Jadassohn
* Radiation

Micro:
Architecture:
* Usually sheets or lobules separated by fibrovascular stroma
* Dermal based tumor with focal connection to the epidermis or follicular epithelium
* Can appear cystic with central comedo type necrosis

Cytology:
* Classified as poorly, moderately or well differentiated
* Can exhibit squamous metaplasia or focal apocrine differentiation

Molecular:
* May rarely occur in association with Muir-Torre syndrome, an autosomal dominant syndrome characterized by a sebaceous neoplasm (adenoma, sebaceoma or carcinoma) and occasionally keratoacanthoma associated with a visceral malignancy

IHC:
Androgen receptor
Adipophilin - membranous vesicular pattern (a granular pattern is considered negative)
Keratin
EMA
LeUM1
Ki67 - increased relative to sebaceous adenoma and sebaceoma
p53 - increased relative to sebaceous adenoma and sebaceoma
BerEP4

Question 5

Nevus sebaceus of Jadassohn

Answer 5

• Nevus sebaceus of Jadassohn (sebaceous nevus, organoid nevus) is a hamartoma that is histologically characterized by a complex and abnormal proliferation of epidermis and adnexal structures
• Commonly presents at birth as a single yellow patch of alopecia on the scalp, becomes verrucous during childhood and puberty and shows variable enlargement during adulthood (due to development of a range of often benign and occasionally / rarely malignant tumors)

Can be associated with the following syndromes:
* Phacomatosis pigmentokeratotica
* SCALP syndrome (sebaceus nevus syndrome, CNS symptoms, aplasia cutis, limbal dermoid and pigmented nevus with neurocutaneous melanosis)
* Linear sebaceus nevus syndrome, i.e Schimmelpenning–Feuerstein–Mims syndrome (organoid nevi, abnormalities of the central nervous system and eyes, oral lesions and skeletal defects)

Micro:
* Well circumscribed and complex proliferation and alteration of epidermis and adnexal structures that often changes with age
* Prepubertal lesions are broad with primitive hair follicles and markedly decreased terminal hairs (hair follicles are usually vellus)
* Sebaceous glands can be increased or decreased based on the age and associated hormonal effect and can show an abnormal distribution and configuration; they can also be located higher than normal in the dermis without connection to a hair follicle and with direct opening onto the epidermal surface

Additional features are variably seen and include:
* Increased acanthosis, papillomatosis and basal epidermal melanin pigmentation
* Presence of an inflammatory infiltrate
* Ectopic apocrine glands (up to half of cases and occasionally dilated)
* Anomalous ductal sweat gland structures resembling eccrine hyperplasia
* Secondary neoplasms occur, namely trichoblastoma-like tumor, trichilemmoma, syringocystadenoma papilliferum and sebaceous gland neoplasms

Molecular:
* Associated with activating HRAS p.Gly13Arg and KRAS p.Gly12Asp mutations