Current Diagnosis and Treatment Options for Cutaneous Adnexal Neoplasms with Follicular Differentiation

Abstract

Neoplasms derived from follicular tissue are extremely rare. Clinically, they are reported as non-symptomatic, slow-growing nodules. These lesions are mainly benign, but the malignant type can occur. Mainly middle-aged people (50-60 years of age) are affected. These carcinomas are mainly localized on the head and neck or torso. They can be locally aggressive and infiltrate surrounding tissue and metastasize to regional lymph nodes. In the minority of cases, distant metastases are diagnosed. Quick and relevant diagnosis is the basis of a treatment for all types of tumors. The patient's life expectancy depends on multiple prognostic factors, including the primary tumor size and its mitotic count. Patients should be referred to a specialized skin cancer center to receive optimal multidisciplinary treatment. This article tries to summarize all the information that is currently available about pathogenesis, diagnosis, and treatment methods of follicular tumors.

Keywords: adnexal; diagnosis; follicular tissue; neoplasm; treatment; tumors.

Figure 1

Division of tumors with follicular differentiation.

Figure 2

Disturbance of intracellular signaling pathways. Single arrow—activation; double arrow—activation by inhibition; inhibition arc—inhibition. Akt—protein kinase B; APC—adenomatous polyposis coli; CDK—cyclin-dependent kinase; CDKN—cyclin-dependent kinase inhibitor; CREB—cAMP response element-binding protein; CYLD—ubiquitin carboxyl-terminal hydrolase; DVL—dishevelled; ERK—extracellular signal-regulated kinase; EGF—epidermal growth factor; FGF—fibroblast growth factor; GLI—glioma-associated oncogene; Grb—growth factor receptor-bound protein; GSK—glycogen synthase kinase; LEF-1—lymphoid enhancer-binding factor-1; MEK—mitogen-activated protein kinase kinase; mTOR-mechanistic target of rapamycin; NEMO-NF-Kappa-B essential modulator; NF-κB-nuclear factor kappa-light-chain-enhancer of activated B cells; p90RSK—90 kDa ribosomal s6 kinases; PI3K-phosphoinositide 3-kinase; PKC-protein kinase C; PLC-phospholipase C; PTCH1—patched 1; PTEN—phosphatase and tensin homolog; RB—retinoblastoma protein; SHH—sonic hedgehog; SMO—smoothened; SOS—Son of Sevenless; TCF—transcription factor.

Figure 3

Malignant tumors with follicular differentiation. (A1–A3) trichilemmal carcinoma, composed of atypical cells with clear cells with sharply defined borders, prominent nucleoli, and frequent mitoses and [(A1) (400×, HE)], PAS-positive cytoplasm [(A2) (400×, PAS)], it shows CK14 expression, which is characteristic for follicular infundibulum differentiation (A3); (B1–B3) proliferating trichilemmal tumor, well-circumscribed nodule with trichilemmal keratinization without granular layer [(B1) (20×, HE), (B2) (200×, HE) and (B3) (400×, HE)]; (C1–C3) pilomatrical carcinoma, poorly circumscribed tumor with deep dermis invasion fields [(C1) (20×, HE)], solid aggregates of immature basaloid cells with less abundant shadow cells [(C2) (100×, HE)], neoplastic cells have scant cytoplasm, vesicular nuclei and high mitotic activity [(C3), (200×)].

Figure 4

Adjuvant radiotherapy after surgical excision with positive microscopical margins of pilomatrix carcinoma localized on the cervical skin. The intensity-modulated radiotherapy technique with simultaneous integrated boost was used. The patient received 59.4 Gy in 1.8 Gy fractions for regional lymph nodes and 66 Gy in 2 Gy fractions for high-risk clinical target volume that covered tumor bed and surrounding skin.

Figure 5

Benign tumors with follicular differentiation. (A1–A3) trichoblastoma: tumor composed of basaloid cells and specific stromal component resembling follicular mesenchyme [(A1) (20×, HE), (A2) (200×, HE)], the epithelial cells are strongly positive for BerEP4, it may be helpful in differential diagnosis with microcystic adnexal carcinoma which is infiltrative and negative for BerEP4 [(A3) (20×, BerEP4)]; (B1–B3) pilomatricoma, well-circumscribed lesion [(B1) (40×, HE)] with basophilic tumor with prominent cornification and numerous shadow cells [(B2) (100×, HE)], in older lesions calcifications and ossifications may be numerous [(B3) (20×, HE)]; (C1–C3) trichilemmoma: trichilemmoma, clear cell differentiation and prominent basement membrane, [(C1) (40×, HE), (C2) (200×, HE), (C3) (400×, HE)].