Introduction: Pilomatrix carcinomas (PMXCs) are uncommon, locally aggressive tumors with high recurrence rates, metastatic potential, and fewer than 130 cases reported in the literature. Typically, they present as an unassuming, firm, dermal swelling and therefore are frequently mistaken for more common, benign masses, leading to undertreatment which can cause local invasion and metastatic spread. Diagnosis relies on excision with pathologic analysis; however once diagnosed, there are no current recommendations to guide treatment or surveillance for recurrence or metastases. Case Presentation: Here, we present a case of one of these rare tumors. Our case describes a 1.5 × 2.5 cm firm, mobile mass at the supraorbital rim in an otherwise healthy, young patient. Prior to removal, we suspected a benign pathology; however, excision proved difficult and pathologic diagnosis was consistent with PMXC. Following discussion with tumor board, decision was made to perform Mohs micrographic surgery and staging via CT scans with regular follow-up and surveillance scans. Conclusion: PMXCs are exceedingly rare diagnoses and present like many benign lesions. Therefore, we elected to document this case to encourage providers to keep these biologically aggressive tumors on their list of differential diagnoses in an unsuspecting mass, as well as to provide our own recommendations for treatment and screening for recurrence and metastatic spread.

Pilomatrix carcinomas (PMXCs) are a rare, locally aggressive, tumor with high recurrence rates and metastatic potential [1‒3]. First described in 1980, they are theorized to originate from the outer root of the hair follicle sheath [1, 2, 4]. Patients typically present with a solitary, asymptomatic, firm, dermal swelling that is slow growing, followed by a period of rapid growth [2, 4]. Fewer than 130 cases have been reported. Most occur in the head/neck region, in Caucasian males, and have bimodal age distribution [2]. Because PMXC is present like many benign masses, coupled with their rarity, they often go misdiagnosed which can result in local invasion and/or eventual metastatic spread [5‒7].

Debate exists whether PMXCs occur as a de novo mutation or if they undergo malignant transformation in the setting of a previous pilomatrixoma [5]. Both lesions have mutations in the CTNNB1 gene which affects the WNT signaling pathway and encodes B-catenin formation [5]. Some case reports describe the development of a PMXC the setting of an established pilomatrixoma supporting the latter theory, although neither have been established as fact [5, 8]. Currently, there are no set guidelines regarding initial treatment or protocol for long-term follow-up/surveillance.

Although PMXCs are rare, they have recurrence rates up to 59% and can invade locally and/or metastasize to distant sites. Despite their benign facade, they are biologically aggressive; therefore, providers must be vigilant in appropriately treating the initial lesion and screening for recurrence and metastatic spread.

We present a healthy, 41-year-old male with a “cyst above his eye.” The lesion suddenly appeared 17 months prior to presentation, was stable, and then rapidly enlarged over a few weeks. He denied pain, changes in sensation or vision, history of facial trauma or surgery, or family history of cutaneous cancers.

Examination revealed a 1.5 × 2.5 cm firm, mobile, mass at the lateral, left supraorbital rim, shown in Figure 1. Differential diagnoses included trichilemmal cyst, epidermal inclusion cyst, and dermoid cyst; therefore, 1 week later, he underwent simple excision of the mass. Surprisingly however, the mass was adherent to adjacent tissue with poorly defined dissection planes. The difficult dissection prompted a high clinical suspicion for an anomalous diagnosis.

Fig. 1.

Patient at time of initial presentation. Patient reported 17-month history of slow-growing mass above left eye which had recently undergone a period of rapid growth. Mass was firm and mobile, measuring 1.5 × 2.5 cm. a Anterior view. b Lateral view.

Fig. 1.

Patient at time of initial presentation. Patient reported 17-month history of slow-growing mass above left eye which had recently undergone a period of rapid growth. Mass was firm and mobile, measuring 1.5 × 2.5 cm. a Anterior view. b Lateral view.

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Histopathology revealed uniform basaloid cells and “ghost cells” in which only shadows of nuclei remained, basaloid cells with infiltrative patterns and aggregates with central necrosis, shown in Figures 2 and 3. Mib1 (Ki-67) showed a high proliferative index in the infiltrative areas and areas of necrosis, shown in Figure 4. Together, this was consistent with PMXC arising in a pilomatrixoma.

Fig. 2.

a–c Hematoxylin and eosin sections show a poorly circumscribed, asymmetrical tumor consisting of pleomorphic basaloid cells and eosinophilic shadow cells seen at the center of these basaloid islands (×4, a). Prominent nucleoli are also noted, with oftentimes mild cytologic atypia (×10, b, ×20, c).

Fig. 2.

a–c Hematoxylin and eosin sections show a poorly circumscribed, asymmetrical tumor consisting of pleomorphic basaloid cells and eosinophilic shadow cells seen at the center of these basaloid islands (×4, a). Prominent nucleoli are also noted, with oftentimes mild cytologic atypia (×10, b, ×20, c).

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Fig. 3.

Beta-catenin positively stains basaloid tumor cells.

Fig. 3.

Beta-catenin positively stains basaloid tumor cells.

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Fig. 4.

Mib1 (Ki-67) staining demonstrates a high proliferative index in the infiltrative areas and areas of necrosis.

Fig. 4.

Mib1 (Ki-67) staining demonstrates a high proliferative index in the infiltrative areas and areas of necrosis.

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Extensive literature review failed to uncover clear guidelines for treating or managing these patients. Therefore, this case was presented at our monthly multi-disciplinary conference. The consensus was to perform Mohs micrographic surgery (MMS) which took place 5 weeks after initial presentation. The planned excision was 2.5 × 3.3 cm allowing for margins of 0.5 cm. Final defect measured 2.5 cm × 3.5 cm, shown in Figure 5.

Fig. 5.

a Markings prior to MMS excision with planned margins of 0.5 cm. b Final defect measuring 2.5 cm × 3.5 cm. Of note, patient opted for healed by secondary intent.

Fig. 5.

a Markings prior to MMS excision with planned margins of 0.5 cm. b Final defect measuring 2.5 cm × 3.5 cm. Of note, patient opted for healed by secondary intent.

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Staging was performed with computed tomography (CT) of the neck and chest. This allowed for assessment of lymph nodes and revealed an enlarged cervical node. Fine-needle aspiration demonstrated benign pathology. Despite being offered reconstructive options, the patient opted to heal secondarily. He followed up with our team 6 months later and again at the 1-year mark with repeat chest and head/neck CT scans which demonstrated stable lymph node findings and no evidence of recurrence. The current plan for surveillance is to continue annual clinic visits with associated repeat scans to monitor for changes or progression.

PMXCs are a rare, locally aggressive tumor. The largest literature review describes only 125 cases [5, 9]. These tumors more commonly affect males (3:1–5:1), are located in the head/neck region, are located on the left (67%), and occur in a bimodal age distribution (6th and 7th decades, and first 3 decades) [2, 4]. Their size averages 3–4 cm; however, lesion as large as 14.5 cm has been reported [2, 5].

There is no consensus regarding the underlying pathophysiology of PMXC. Some researchers suggest they are the result of de novo mutations while others theorize that malignant transformation occurs in an established pilomatricoma. One study reported approximately 50:50 split of PMXC that rapidly grew (N = 10), supportive of a de novo mutation, while the other half had a slowly enlarging lesion ± a long latency period before suddenly undergoing rapid growth (N = 13), favoring the malignant transformation theory [5]. Pilomatricomas and PMXC have similar mutations in exon 3 of CTNNB1, a gene that encodes B-catenin. This commonality hints at a potential linkage, supporting the idea that PMXC may in fact represent a devolution of a pilomatricoma [9].

Clinically, patients present with an asymptomatic, firm, painless mass. This is like a myriad of benign skin lesions, and given PMXC’s low incidence, they are often mistakenly initially diagnosed as lipomas, dermoid cysts, or epidermal inclusion cysts [7]. A 2016 review found that 0/20 PMXCs were correctly diagnosed in the clinic [5]. Similarly, on initial presentation our differential diagnoses were varying benign lesions. Despite an initial nonthreatening presentation, these tumors act in a biologically aggressive manner. First evident during excision, these masses infiltrate and adhere to surrounding tissues, resulting in unclear dissection planes. Although final diagnosis is usually made on histopathology, if dissection proves difficult, providers should have high preliminary clinical suspicions for malignancy.

Pathologically, PMXCs exhibit many classic features of any malignant cutaneous lesion including poor circumscription, asymmetry, and cellular atypia with increased mitoses [5, 10]. Compared to their benign counterpart, PMXCs often show basaloid cell predominance, tumor necrosis, and perineural and lymphovascular invasion [11]. Importantly, neither molecular nor immunohistochemical methods distinguish PMXCs from pilomatricomas; rather, they must be distinguished based on histopathology [10].

Differential diagnoses on pathology include proliferating pilomatricoma and aggressive pilomatricoma. The former are well-circumscribed, symmetric lesions, although they also demonstrate mostly basaloid cells with scant cytoplasm, hyperchromatic nuclei, and mitotic activity [10]. Aggressive pilomatricomas have an infiltrative growth pattern, although they paradoxically demonstrate mild cytologic atypia despite high mitotic activity [10].

Following diagnosis, next steps in management are unclear. There is no established standard for metastatic workup, treatment, or screening for recurrence. These tumors can metastasize even in the setting of a previously treated PMXC [6, 7]; therefore, workup for metastasis is essential. The most common site for spread is to the lungs or regional lymph nodes [6] though spread to bones and viscera has been reported [5, 12]. There is no consensus on the most effective imaging modality to screen for metastatic lesions. Options include CT, MRI, or PET scan. In this case, we performed non-contrast CT of the head/neck to evaluate for locoregional lymph node metastases to the neck; however, MRI may be more appropriate for larger or extremity lesions. Additionally, given the propensity for these tumors to metastasize to the lungs, CT chest should be considered.

Regarding treatment, simple excision is associated with recurrence rates up to 60%, 1–3; therefore, most literature suggests complete excision with wide margins (4–30 mm) [1, 5]. MMS may be the best option, as it offers the balance of precise margin control while limiting morbidity and the need for extensive reconstruction. There may be a role for radiation, especially for lymph node involvement, recurrence, or metastatic lesions. Radiation therapy should also be considered in the case of systemic disease for palliative management [6, 7, 12]. On the contrary, limited evidence exists in support of chemotherapy for primary lesions, and there has been no reported benefit in recurrent or metastatic disease [5‒7].

Following clean margins, patients require vigilant screening for recurrence and metastatic spread. Recurrence can occur as early as 2 months following excision with clear margins. Unfortunately, there is a paucity of literature describing the optimal way to perform this necessary surveillance. Case reports have previously described how pilomatrixomas [13] and pilomatrical carcinomas [14, 15] are present on the various imaging modalities; however, no studies comparing modalities or describing which is superior currently exist. This further highlights the lack of clear guidance that exists in terms of managing this malignancy.

Our recommendations for management of these patients following histopathologic diagnosis are as follows: patients must undergo excision with clear margins. We favor use of MMS over wide excision given the propensity of these lesions to affect cosmetically sensitive areas; however, wide excision is reasonable in non-cosmetically sensitive areas. We recommend screening for spread to locoregional lymph nodes via imaging, ± CT chest to evaluate for pulmonary metastasis. Following clear margins, we suggest routine follow-up (every 6–12 months for the first 2 years) with repeat CT imaging for screening of recurrence and metastatic spread. In the case of positive nodes or metastatic spread, referral to radiation oncology should be offered for consideration of radiotherapy for treatment or even palliative measures.

This case report adds to the small body of existing literature surrounding the presentation of a rare disease which is disguised by a benign facade. Other strengths of our report include our suggested management strategy when presented with this rare diagnosis, something that is novel compared to prior case reports. Limitations mainly surround the limited number of published cases which restrict our capacity to make conclusions or generalizations.

Given their low incidence, a presentation that mimics many benign processes, and their capacity to metastasize/recur, we urge providers to include PMXC as a differential when presented with unassuming skin lesions. Following histopathological diagnosis, we recommend patients to undergo full workup including imaging of regional nodes ± CT chest to evaluate for pulmonary metastases. Treatment should be centered on wide excision, with consideration given to MMS in cosmetically sensitive areas. For recurrent or metastatic lesions, consider the role of radiation [7, 8, 12]. Finally, long-term surveillance should involve screening at 6–12-month intervals given the high recurrence rates.

When someone tells you that you have the C word your mind goes numb. You automatically think the worst. It is so important to listen to your doctors and do exactly what they ask. Dr. Bernstein and Dr. Chen both told me to take 4–6 weeks off. No working, driving, heavy lifting, hard physical activity, etc. Pretty much just stay on the couch. For someone that is always on the go, it was a strange thing to do. That combined with keeping the area clean and bandaged is why I think I healed so well. I guess a little bit of luck was involved as well.

The only other thing I can offer to the next person is to stay positive and have no other option in your mind other than to beat it and move on with your life. Please tell everyone involved, those I met and those I haven't that I am truly grateful for each and every one of you. I wish you all nothing but the best and can't thank you enough for all that you did for me.

Written informed consent was obtained from the patient for publication of the details of his medical case and any accompanying images. This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

C.A.S.: primary manuscript author, performed literature review and comprised case report with exception of pathology section, and assistant surgeon in case. L.Y.: author of pathology section, assisted in analyzing and choosing pathology specimen slides, and reviewed final draft. M.H.: senior pathology consultant, interpreter of pathology slides, assisted in analyzing pathology specimen slides, and reviewed final draft. R.B.: editor and reviewer of case report/manuscript. M.L.B.: surgeon and main collaborator in case report including editing and reviewing.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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