four instead of the normal two chromosomes for some but not all chromosomes), single chromosome gains for several chromosomes, and loss of heterozygosity in the p arms of chromosomes 1 and 11 in the first case and in the second case a loss of the p arm in chromosome 10, lose of chromosome 14, and lose of a portion of the q arm of chromosome 22q. These two cases along with recurrent EGFR gene abnormalities strongly support the notation that FHI is as neoplastic tumor. Diagnosis
The diagnosis of FHI is dependent on its presentation as a subcutaneous tumor that often occurs in individuals at birth or ages <1–2 years old; its highly characteristic histopathology consisting of fibroblast/myofibroblast, adipose tissue, and myxoid zones; and its content of tumor cells which have one of the EGFR gene mutations described in the previous section. The combination of these factors clearly distinguishes FHI from three recently defined tumors (i.e. fibroblastic connective tissue nevus, medallion-like dermal dendrocyte hamartoma, and plaque-like CD34-positive dermal fibroma) as well as various pediatric spindle-shaped cell neoplasms. Tumor imaging methods such as magnetic resonance imaging may also be helpful in suggesting that a tumor is an FHI. Treatment and prognosis
FHI tumors, if left untreated, have been documented to grow for as long as ~5 years following their diagnosis. The treatment of choice for these tumors is complete surgical excision with clear margins (i.e. with removal of all tumor tissue).
Tisotumab vedotin, sold under the brand name Tivdak, is an antibody-drug conjugate used to treat cervical cancer. It is a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), a potent inhibitor of cell division. Tisotumab vedotin was approved for medical use in the United States in September 2021. It is administered by infusion into a vein every 3 weeks.Tisotumab vedotin is the international nonproprietary name (INN). Adverse effects
In the United States, Tivdak carries a black box warning for ocular toxicity, which occurs in up to 60% of treated patients. In clinical trials, the most common forms of ocular toxicity were dry eye, conjunctivitis, corneal damage, and blepharitis.To prevent eye damage, premedication with three different types of eye drops—a topical corticosteroid, a vasoconstrictor,  and artificial tears—is recommended before each infusion, as well as the use of cold packs over the eyes.Other very common adverse effects include bleeding (occurring in approximately 60% of patients, most often nosebleed) and peripheral neuropathy (42% of patients). Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs. Mechanism of action
The antibody portion of tisotumab vedotin (tisotumab) binds to and forms a complex with tissue factor, a molecule expressed on the surface of cancer cells. This complex is then taken up into the cell, where tisotumab vedotin is broken down by proteolytic cleavage, releasing MMAE, which stops the cell cycle and kills the cell by apoptosis.