Primary Alopecia Neoplastica: A Novel Case Report and Literature Review

Abstract

Alopecia neoplastica (AN) is caused by neoplastic cells damaging hair follicles, resulting in patchy hair loss like cicatricial alopecia and alopecia areata. AN has predominantly described cutaneous metastasis to the scalp from primary visceral malignant tumors. Less frequently, AN results from a primary scalp neoplasm. Compared to “secondary AN,” there is a paucity of literature on “primary AN.” Herein, we present a comprehensive literature review of primary AN and introduce a unique case of amelanotic melanoma causing primary AN. Including our presented case, 11 cases of primary AN have been reported with causative scalp neoplasms including angiosarcoma, hemangioendothelioma, syringomatous carcinoma, ectopic extramammary Paget's disease, and primary desmoplastic melanoma. 27.3% (3 of 11) of cases were misdiagnosed and treated for a primary alopecia, and 36.4% (4 of 11) of lesions were present for multiple years or an unknown amount of time, likely due to difficulty in recognizing scalp lesion or misdiagnosis. All patients required surgical excision with 36.4% (4 of 11) requiring chemotherapy, radiation, or photodynamic therapy. Two patients with scalp angiosarcoma died from their aggressive disease. Due to the risks of malignant primary AN if allowed to progress, primary AN should be considered in patients presenting with scarring alopecia.

Established Facts

• Alopecia neoplastica (AN) is a rare, scarring alopecia in which neoplastic cells destroy follicular orifices and replace follicles with fibrous tracts.

• AN has predominantly described alopecia secondary to cutaneous metastasis to the scalp from primary visceral malignant tumors, most commonly the GI tract, breast, kidney, and lung.

• The less frequently reported primary AN results from dermal infiltration by a neoplasm originating in the cutaneous scalp.

Novel Insights

• In a patient with focal, scarring alopecia, primary and secondary AN should be considered. Reported causative scalp neoplasms of primary AN include angiosarcoma, hemangioendothelioma, syringomatous carcinoma, ectopic extramammary Paget's disease, and primary desmoplastic melanoma.

• Amelanotic melanoma has not previously been reported as a cause of primary AN. Herein, we present a unique case of amelanotic melanoma of the scalp causing scarring alopecia.

• Primary AN from malignant neoplasms carries considerable morbidity and mortality risk, compounded by frequent misdiagnosis as cicatricial alopecias or AA. If misdiagnosed, patients may not receive the appropriate malignancy treatment for months to years.

Introduction

Alopecia neoplastica (AN) is a scarring alopecia in which neoplastic cells destroy follicular orifices and replace follicles with fibrous tracts [1, 2]. It is a rare diagnosis with variable presentation. Thus, the differential diagnosis for AN regularly includes cicatricial alopecia and alopecia areata (AA). Cicatricial alopecias are considered due to visible follicular destruction in areas of hair loss while AA is considered due to the often patchy presentation in AN.

Cohen et al. [3] first defined AN in 1961 in a case report of 3 women with patchy, erythematous scalp hair loss. Pathology confirmed alopecia secondary to breast cancer scalp metastasis. The term “alopecia neoplastica (AN)” has since predominantly described this pattern of cutaneous metastasis to the scalp that presents clinically as a patch or plaque of hair loss [4].

Since 1961, AN has been widely reported and reviewed. A systematic review by Paulino et al. [5] of 118 reports of AN revealed 123 cases from metastatic visceral malignancies. The most common primary tumor sites were the GI tract, breast, kidney, and lung. AN has also described cases of localized alopecia secondary to a primary neoplasm of the scalp [2, 6]. Referring to these cases simply as AN, however, may be misleading as the alopecia is caused by a primary scalp tumor rather than a metastasis to the scalp. After review of such cases, it was suggested that AN be split into “primary AN” and “secondary AN” depending on the neoplasm source [4]. In both cases, scalp hair loss is due to dermal infiltration by tumor cells, with primary AN resulting from a neoplasm originating in the cutaneous scalp and secondary AN occurring from a malignancy metastasizing from a distant site [4].

Given the paucity of reports of primary AN in the literature, we present a comprehensive literature review of primary AN. We also introduce a unique case of amelanotic melanoma (AMM) causing primary AN.

Primary AN

Primary AN can result from both benign and malignant neoplasms. Benign neoplasms (Table 1) may result in scalp alopecia due to a clinically unapparent or minimally apparent neoplasm, as described by Scheinfeld [7]. In these cases, scarring alopecia generally presents the largest risk to the patient.

Table 1.

Benign neoplasms causing primary AN [7]

Benign neoplasms causing primary AN
− Nerve sheath myxoma
− Neuroma
− Nevocellular nevus
− Osteomyoma-like tumor
− Syringomas
− Trichoepithelioma AN, alopecia neoplastica.

Primary AN from malignant neoplasms carries considerable morbidity and mortality risk, compounded by frequent misdiagnosis as cicatricial alopecias or AA. If misdiagnosed, patients may not receive the appropriate malignancy treatment for months to years. Additionally, inappropriate treatment with topical or systemic immunosuppressants can worsen an existing malignancy.

Malignant neoplasms of the scalp are relatively uncommon. Approximately 2% of epithelial tumors and slightly more of somatic tumors occur on the scalp [8]. In general, primary scalp tumors include squamous cell carcinoma (SCC), basal cell carcinoma (BCC), melanoma, fibrosarcoma, embryonic rhabdomyosarcoma, angiosarcoma, leiomyosarcoma, liposarcoma, lymphosarcoma, reticulum cell sarcoma, adenocarcinoma, adenocystic BCC, and leukemic infiltrations [8]. Not all, however, are associated with alopecia.

In the current literature, there have been relatively few reported cases of alopecia resulting from primary scalp malignancy or primary AN. Herein, we describe the malignancies of reported primary AN that should be considered when evaluating a patient with focal scarring alopecia. Table 2 reviews the clinical characteristics of each type of primary AN tumor.

Table 2.

Clinical presentation of reported cases of alopecia secondary to primary scalp malignancy

Case No.	Gender	Dx age	Lesions,	Lesion duration	Scalp site	Size	Clinical features	Pathology	Primary AN malignant neoplasm	Incorrect tx prior to biopsy?	Ref
1	F	83	Multiple	6 months	Bilateral parietal	Unspecified	Areas of localized scarring, purpuric violaceous patches and an indurated angiomatous mass at right parieto-occipital scalp	Moderately differentiated angiosarcoma (stage 2 or 3)	Angiosarcoma	n/a	[17]
2	F	77	Multiple/diffuse	4 months	Frontal, temporoparietal, vertex	Large, unspecified	Erythematous skin with destroyed follicular orifices and scattered, adherent, serous crust	Diffuse dermal involvement with neoplastic tissue; endothelial cells obliterating adnexal structures and forming irregular vascular channels lined by abnormal cells	Angiosarcoma	Yes − oral prednisone, “topical medication”	[18]
3	F	24	1	Several months	Left temporoparietal scalp	3×2 cm	1.5-cm firm nodule within a 3×2-cm ill-demarcated violaceous patch	Heterogeneous components characteristic of hemangioendothelioma	Hemangioendothelioma	n/a	[23]
4	F	50	1	“Years”	Unspecified scalp	11×7 cm	Smooth, hairless, erythematous area with several 3- to 5-mm deep palpable nodules	Well-differentiated syringomatous carcinoma with aggregations of neoplastic cells extending deep into the reticular dermis; neoplastic cells showing moderate nuclear atypia	Syringomatous carcinoma	Yes − multiple for presumed alopecia areata	[26]
5	F	57	1	Unknown	Right parietal	5×3 cm	Poorly circumscribed, erythematous plaque, with patchy alopecia	Epidermal pagetoid infiltration by atypical single and nested cells with amphophilic cytoplasm and nuclear hyperchromasia, extending along adnexa and the hair matrix. No dermal invasion	Ectopic EMPD	n/a	[6]
6	F	73	1	5 months	Unspecified scalp	20 mm	Solitary nodule with surrounding alopecia	Cohesive nests and single enlarged cells with round to oval nuclei and prominent nucleoli within epidermis; focal mucin vacuoles confirmed with PAS-D staining; nodular BCC confirmed elsewhere in excision. No dermal invasion	Ectopic EMPD with concurrent nodular BCC	n/a	[37]
7	M	86	1	10 years	Right parietal	8.5×6 cm	Erythematous plaque with alopecia and small portion of ulceration	Epidermal pagetoid infiltration by atypical round, single, and nested cells with eosinophilic cytoplasm and nuclear hyperchromasia. No dermal invasion	Ectopic EMPD	n/a	[38]
8	M	50	1	5 months	Left frontal	“Several cm”	Mildly erythematous plaque	Desmoplastic malignant neurotropic melanoma, 2.1-mm thickness, Clark level 5 with probably perineural involvement, S100+	Primary desmoplastic melanoma	n/a	[2]
9	F	66	1	“Few months”	Superior parietal	2 cm	2-cm, firm, white, hairless tender plaque with indistinct borders	Combined desmoplastic and conventional melanoma, 8.5-mm Breslow, S100+, Clark level 5, focal perineural invasion	Primary desmoplastic melanoma	Yes − topical medications for AA versus LPP	[65]
10	F	59	1	4–6 months	Left vertex	1 cm	Pink, firm, hairless plaque	Desmoplastic melanoma, S100+	Primary desmoplastic melanoma	n/a	[65]
11	F	73	1	Unknown	Vertex	1–2 cm	Asymptomatic pink plaque with surrounding 2- to 6-mm scattering pink scaly papules	Severely atypical intraepidermal lentiginous and nested melanocytic proliferation with confluent growth and pagetoid spread, highlighted by a Melan-A stain. No dermal invasion	Amelanotic melanoma	n/a	Our case

AN, alopecia neoplastica; EMPD, extramammary Paget's disease; BCC, basal cell carcinoma.

Angiosarcoma

Angiosarcoma is a rare, malignant tumor of the vascular or lymphatic endothelium that can occur anywhere, but most commonly on the scalp and face [9]. It makes up 15% of all head and neck sarcomas [10] and approximately 2% of all soft-tissues sarcomas, which themselves account for only 1% of all malignancies [11]. Angiosarcoma presents primarily in males (2:1) and elderly patients [12]. Specifically, scalp angiosarcoma occurs most commonly in elderly, white males [9]. Clinical presentation can be quite variable, innocuous, and may mimic other benign conditions [13].

Cutaneous angiosarcomas are aggressive, difficult-to-treat malignancies with reported 5-year overall survival rates ranging from 9 to 30% [10, 15, 16]. Studies comparing outcomes of scalp versus facial angiosarcoma indicate a worse prognosis in scalp disease [9, 14]. In one study of 50 patients with scalp or facial cutaneous angiosarcoma, the 5-year recurrence-free survival rate was 5 and 27% and the overall survival rate was 9 and 26% for scalp and facial disease, respectively [14]. In this study, scalp tumors were larger at diagnosis compared to facial, most likely due to delayed discovery. While the optimal treatment is not yet defined, complete surgical resection with wide margins is preferred for localized disease, and chemotherapy is used for metastatic disease and/or when resection is not possible [15].

In the current English language literature, 2 cases of angiosarcoma primary AN have been reported [16, 17] (Table 2). Patients presented with multiple patches to diffuse scalp hair loss. Both cases pathologically demonstrated tumor-associated scarring hair loss with diffuse dermal involvement of neoplastic tissue (Table 2). In 1 case, biopsy also showed increased miniaturized and telogen-phase hair follicles. As these are characteristic of androgenic alopecia (AGA), AGA was considered but was determined to be less likely due to hair loss occurring primarily within the violaceous angiosarcoma lesions [16].

Like many cases of aggressive cutaneous angiosarcoma, both patients with angiosarcoma primary AN had poor treatment response and died from their disease (Table 3). Due to the progressive nature and poor prognosis of scalp angiosarcoma, early diagnosis is imperative. This diagnosis, therefore, should be considered in patients, especially elderly males, who present with scarring alopecia.

Table 3.

Treatment and outcomes of reported cases of alopecia secondary to primary scalp malignancy

Case No.	Gender	Dx age	Primary AN malignant neoplasm	Lymph nodes sampled	Evidence of metastasis	Treatment	Reported patient outcome	Ref
1	F	83	Angiosarcoma	No	No	Chemotherapy without response	Death	[17]
2	F	77	Angiosarcoma	No	Not at initial presentation, metastatic disease later in course	Radiation (6 weeks) resulting in tumor resolution, followed by reoccurrence in 7 months	Death	[18]
3	F	24	Hemangio-endothelioma	No	No	Surgical excision with 2- to 3-cm surgical margin and split-thickness skin graft	Survival	[23]
4	F	50	Syringomatous carcinoma	No	No	Surgical excision	Unknown	[26]
5	F	57	Ectopic EMPD	No	No	Staged surgical excision	Survival	[6]
6	F	73	Ectopic EMPD with nodular BCC	No	No	Surgical excision (originally for BCC)	Unknown	[37]
7	M	86	Ectopic EMPD	No	No	Photodynamic therapy (3 sessions every 4 weeks); near-complete remission within 3 months, maintained at 1-year follow-up	Survival	[38]
8	M	50	Primary desmoplastic melanoma	No	Not at initial presentation, local reoccurrence and metastatic disease later in course	Multiple rounds of surgical excision and radiation for primary disease, local reoccurrence, and metastatic disease	Survival	[2]
9	F	66	Primary desmoplastic melanoma	No	No	Wide surgical excision	Survival	[65]
10	F	59	Primary desmoplastic melanoma	Unknown	Unknown	Surgical treatment at outside facility/lost to follow-up	Unknown	[65]
11	F	73	Amelanotic melanoma	No	No	Staged surgical excision	Survival	Our case

AN, alopecia neoplastica; EMPD, extramammary Paget's disease; BCC, basal cell carcinoma.

Composite Hemangioendothelioma

Composite hemangioendothelioma (HE) is a rare, low-grade vascular tumor first described in 2000 [18] with 38 total cases reported as of 2015 [19]. Composite HE histologically consists of 2 or more different types of HE resulting in tumors with varying combinations of benign, low-grade malignant, and malignant vascular components [18]. Composite HE occurs primarily in adults [19], but has also been reported in infants [20], children, and teenagers [21].

Typically, composite HE presents as a poorly defined swelling or infiltrative mass on a distal limb, which can be flesh-colored, red, or purple-black and may become scaly or hemorrhagic [22]. Of the 38 reported cases as of 2015, only 2 (5.2%) occurred on the scalp [19, 23] with one presenting with alopecia [22] (Table 2). While surgical excision is regularly curative, local recurrence is common [19]. Metastasis risk is low but may occur years after primary excision [18, 24]. As of 2015, no tumor deaths had been reported in composite HE [19].

Of the few cases of primary AN in the current literature, one was a case of composite HE (Table 2). The patient presented with a 1.5-cm firm nodule within a 3 × 2 cm ill-demarcated violaceous patch on the scalp that histologically had the characteristically heterogeneous components of composite HE [22]. One year following excision, the patient had no reoccurrence of disease (Table 3). Due to the known risk of local reoccurrence, however, patients with composite HE should have regular follow-up.

Syringomatous Carcinoma

Syringomatous carcinoma (SC) is a rare, malignant adnexal tumor that usually occurs as a solitary yellow-white to pink, indurated, subcutaneous nodule or plaque [25] on the scalp or face [26]. In fact, 85% of SC occurs on the head and neck, with particular propensity for the cheek or periorbital region [27]. On histology, SC has tubular features and eccrine differentiation. Differential diagnosis may include SCC, BCC, dermatofibrosarcoma protuberance, and keloid [28]. The slow-growing tumor has potential to metastasize to regional lymph nodes and lungs [29, 30, 31], though rare. Complete surgical excision is required to reduce risk of local reoccurrence [25, 27].

Due to low prevalence, SC may be difficult to recognize by providers, especially in cases of SC primary AN. In the single reported case of SC primary AN (Table 2), in fact, the patient was misdiagnosed with AA for several years. This misdiagnosis was further perpetuated by an initial biopsy that was too superficial to confirm SC [26]. As demonstrated by this case, it is important to consider and evaluate for a neoplastic process in the setting of a slowly enlarging alopecia plaque that does not fit the diagnostic criteria of other forms of alopecia. Evaluation may require an excisional biopsy rather than a punch or a shave biopsy to identify malignant versus benign adnexal neoplasms [26].

Extramammary Paget's Disease

Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that typically presents as pruritic, eczematous plaques in areas with high density of apocrine glands, including the anogenital region and axillae [6]. Approximately 30 cases of EMPD occurring in areas without apocrine glands, known as ectopic EMPD, have been reported [32, 33]. In the English literature, only 5 cases of scalp ectopic EMPD have been reported [6, 34, 35, 36, 37].

Histologically, EMPD is characterized by intraepithelial infiltration of malignant “Paget” cells with glandular differentiation [38]. Paget cells can present as singular cells, small collections or nests, and large sheets of cells occurring in a characteristic pattern predominantly in the lower epidermis with scattered involvement at higher levels [36]. This “pagetoid” growth pattern can progress to involve the entire thickness of the epithelium [39]. With epidermal tumor extension, hair follicles and eccrine ducts can be affected.

Of the 5 reported cases of scalp ectopic EMPD in the English literature [6, 34, 35, 36, 37], 3 had associated alopecia on presentation (Tables 2, 3). While one of these cases was defined specifically as AN [6], the other 2 were described as lesions with associated alopecia [36, 37] (Table 1). In all 3 cases, prompt evaluation for concurrent secondary malignancy was performed following EMPD diagnosis, which were negative [6, 36, 37]. In 1 study of 197 patients with EMPD, 24 and 12% had underlying adnexal carcinoma and concurrent internal malignancy, respectively [39]. Additional studies have also reported an association between EMPD and underlying malignancy ranging from 16 to 48% [40, 41, 42, 43]. This is, therefore, an important consideration with every new EMPD diagnosis, including in the setting of ectopic EMPD resulting in primary AN.

Cutaneous T-Cell Lymphoma, Mycosis Fungoides, Sézary Syndrome

Cutaneous T-cell lymphoma (CTCL) occurs in various forms, some with associated alopecia [44]. The most common type of CTCL is mycosis fungoides (MF), which presents as cutaneous patches and plaques on nonsun-exposed skin [45]. Histologically, MF is characterized by epidermal infiltration of atypical T lymphocytes with cerebriform nuclei [45]. A less common variant of MF is folliculotropic MF (F-MF), which presents with grouped follicular papules, acneiform lesions, and indurated plaques most commonly on the head and neck [45]. On histology, atypical lymphocytes of F-MF infiltrate the follicular epithelium, which may occur with associated mucin deposition (follicular mucinosis) [45, 46]. F-MF is thought to be more aggressive with a worse prognosis compared to conventional MF [47]. Sézary syndrome (SS), a leukemic type of CTCL, presents with generalized erythroderma [45].

MF, F-MF, and SS are all associated with alopecia [44]. In a retrospective study of 1,550 patients with MF/SS, 2.45% had alopecia [44]. Of these, 34% presented with AA-like patchy hair loss in skin without clear MF involvement, with 20% developing alopecia before or within 1 year of MF symptoms. Biopsies in these areas, however, demonstrated histologic evidence of MF. In the remaining 66%, alopecia occurred within clear MF lesions, also confirmed by histology. Total body hair loss only occurred in SS patients with generalized erythroderma. Bi et al. [44] also surveyed 5,000 patients in the National Alopecia Areata Registry and none reported CTCL in any form. This confirmed that MF and AA are distinct pathologies.

Histologic evidence of atypical lymphocytes in areas of alopecia in MF/SS patients suggests that CTCL contributed to hair loss. While this mechanism remains unknown, it is thought that atypical T cells and natural killer cells result in destructive inflammation of the follicular keratinocytes [48]. Another potential mechanism involves follicular damage secondary to follicular mucinosis [49]. Although alopecia in MF/SS is relatively rare [44], it is another example of a primary cutaneous neoplastic process resulting in primary AN. These conditions, therefore, should be considered in patients with new alopecia with and without epidermal change.

Nonmelanoma Skin Cancers

Primary nonmelanoma skin cancers (NMSCs) are not uncommon on the scalp. In a study of 398 Taiwanese patients with malignant scalp tumors, 41.2% were BCC, 16.6% SCC, and only 2% melanoma [50]. The third most common scalp malignancy in this study was metastatic disease (12.8%) [50]. Scalp NMSCs are most common in elderly men who have experienced progressive hair loss and, therefore, chronic sun exposure at the scalp [51, 52]. In fact, in one study of 13,885 tumors treated by Mohs micrographic surgery, 5.7% of all tumors were on the scalp, and 6.0% of male patients had scalp tumors compared to 3.8% of females [53]. The majority of scalp tumors in females were BCCs compared to majority SCCs in males [53].

Although there are no reported cases of NMSC causing primary AN specifically, NMSC should always be included in the differential due to known incidence on the scalp and potential association of aggressive NMSC and head and neck sites [54]. BCC may present as a pink or flesh-colored pearly papule with rolled borders and central ulceration or a pink, scaly macule, patch, or thin plaque on the scalp with or without associated alopecia. SCC on the scalp may also be associated with alopecia within or near an erythematous scaly patch or plaque if SCC in situ. Invasive SCCs are more likely to present as hyperkeratotic papules, nodules, or plaques potentially with ulceration.

Melanoma

While 20% of melanomas occur on the head and neck [55], only 2–5% arise on the scalp [56]. When compared to other body sites, scalp melanoma has higher risk for brain metastasis and poorer prognosis [55, 56, 57, 58, 59, 60, 61]. Worse prognosis is possibly from delayed diagnosis due to poor visibility beneath hair or due to a more aggressive nature supported by scalp anatomy with complex lymphatic drainage, folliculotropism, and extensive vasculature increasing risk of metastasis to intracranial and distant sites [56, 62, 63].

In a multicenter review of 113 cases of scalp melanoma, 79.6% occurred on the scalp with clinically evident alopecia, including thinning (35.4%) and complete scalp hair loss (50.4%) [64]. As expected with the prevalence of AGA in males, there was a striking male predominance in the population. These results align with known risk factors of ultraviolet radiation in melanoma development. Among females, however, 56% of melanomas occurred in hairy areas of the scalp compared to 7% of males. Melanomas in areas of nonthinning hair were more frequently invasive with higher median Breslow depth than those on hairless or thinning areas [64]. These results suggest that there may be mechanisms in addition to UV radiation contributing to melanoma development in hair-dense scalps.

While melanomas are known to occur in hair-dense scalps, only 3 cases of melanoma as a cause of primary AN have been reported (Table 1). All 3 were primary desmoplastic melanoma (DMM) [2, 65].

Desmoplastic Melanoma

DMM comprises only 4% of primary cutaneous melanoma [66]. DMM results from chronic sun exposure rather than intermittent intense exposure. DMMs are mostly found on the head and neck and are frequently nonpigmented, which make them difficult to diagnose. Histologically, DMMs have slender spindle-shaped cells within a fibrotic stroma, which can be mistaken for scar tissue or a benign fibrosing tumor [2].

In a review of 280 cases of DMM [66], there was only 1 case of primary AN. It was postulated that AN resulted from direct fibrosis or release of cytokines from infiltrating tumor cells [66]. Another report presented 2 cases of primary DMM resulting in primary AN [65]. In all 3 of these cases (Table 1), the patients presented with a nonpigmented patch with reduced follicular density or no intact follicles. Biopsy confirmed DMM diagnosis and directed proper treatment.

Current Case Report: Primary AN due to AMM

As demonstrated above, reported cases of melanoma primary AN are limited to DMM. Herein, we present a unique case of AMM causing scarring alopecia.

Case Presentation

A 73-year-old female presented for evaluation of gradual hair thinning and an asymptomatic, 1- to 2-cm pink plaque on the vertex scalp of unknown duration (shown in Fig. 1a). Clustered around the plaque were 2- to 6-mm scattered pink scaly papules, which were not perifollicular. The patient reported no scalp symptoms and denied constitutional symptoms. Findings of the overall physical exam were normal.

Fig. 1.

a A well-demarcated, thin pink plaque on the vertex scalp. b Histopathologic examination of the lesional scalp. HE. ×100. c Histopathologic examination of the lesional scalp. HE. ×200.

The patient had a personal history of several NMSCs and a family history of BCC and melanoma in her sister. Her past medical history included 2 primary breast cancers (ductal carcinoma in situ and an invasive ductal carcinoma), as well as Paget's disease of the breast. For these, she was taking exemestane at the time of evaluation. She also had incidentally found thyroid and pulmonary nodules that were being monitored with serial imaging. Her mother had a history of pancreatic cancer. Genetic testing done in 2017 revealed an isolated ataxia-telangiectasia mutated (ATM) gene mutation, which affects DNA repair and cell-cycle regulation [67].

At the time of initial presentation, the patient was on a course of oral prednisone for rapid hearing loss. Given concerns that this could affect histological findings relevant for diagnosis of inflammatory hair loss, a punch biopsy was deferred until she completed this medication course. Her scalp lesions remained unchanged at the time of biopsy.

Histological assessment revealed a severely atypical intraepidermal lentiginous and nested melanocytic proliferation with confluent growth and pagetoid spread (shown in Fig. 1b), highlighted by a Melan-A stain (shown in Fig. 2). The papillary dermis revealed mild fibrosis and chronic inflammation; no dermal invasion was identified. The findings were consistent with melanoma in situ (shown in Fig. 1c). She underwent staged excision, and final histology showed a T1a AMM (0.3 mm, no ulceration, no mitosis).

Fig. 2.

Melan-A stain of the lesional scalp demonstrating a severely atypical intraepidermal lentiginous and nested melanocytic proliferation with confluent growth and pagetoid spread.

All laboratory testing was within normal limits. CT head demonstrated no intracranial abnormalities. Subsequent biopsy of peripheral lesions revealed actinic keratoses and superficial SCC treated with cryotherapy and excision, respectively. Given her ATM mutation, she follows closely with dermatology and oncology for cancer screenings.

Case Discussion

AMMs are rare, representing an estimated 8% of all melanomas, and can be found among all histological subtypes [68, 69]. At the population level, AMMs have poorer prognosis than pigmented melanoma, due to advanced staging at diagnosis. This is thought to result from delayed recognition, as AMMs lack pigmented features [70].

AMM identification is further complicated by variation in clinical characteristics. Features range from skin-colored to red, occasionally with faint pigmentation at the periphery [69]. More advanced AMMs may be friable or ulcerated [71]. Despite emerging immunomodulatory therapies, systemic treatments are rarely curative [68]. Thus, early recognition and prompt surgical excision remain crucial for best outcomes.

AMM should be part of a broad differential diagnosis to account for nonspecific morphological features. BCC is the most frequent carcinoma worldwide; however, only 2.6% of total BCC cases present on the scalp [72]. The superficial subtype, which most commonly presents on the trunk or limbs, comprises only 8% of all scalp BCCs [72, 73]. Although rare, superficial BCCs have a range of clinical presentations with shared features of AMM. It should be considered in sun-exposed areas, particularly with a patient history of BCC.

In this case, inflammatory alopecia was considered, as the lesion presented in the setting of long-standing hair loss. Lichen planopilaris, the prototypical cicatricial alopecia, has variable presentation, most commonly affecting postmenopausal, Caucasian women [74]. Atrophic, scarred patches range in size and can be accompanied by scaly follicular papules. Approximately half of patients will not report itch or tenderness; however, lichen planopilaris is often accompanied by perifollicular erythema and scale, which was absent on this patient's exam [74].

This case highlights the importance of a broad differential and diagnostic biopsy during the evaluation of alopecia. Although the underlying process may be benign [7], lesions may suggest inflammatory alopecia or a neoplastic process [5, 74, 75] (Table 2). Furthermore, primary or secondary AN is a particularly important consideration in patients with a personal history of malignancy. AMM remains a diagnostic challenge due to nonspecific features on exam. While rare, the case features the importance of considering the diagnosis during evaluation of nonpigmented lesions of varying morphology, as early identification and excision are crucial for best outcomes.

Conclusion

While secondary AN has been well documented and reviewed, there is a paucity of literature on primary AN. Primary AN, although rare, presents unique diagnostic challenges due to the wide variation in clinical features, morphological overlap with common conditions, and lack of malignancy history. In the 11 cases presented here, 27.3% (3 of 11) were misdiagnosed and treated for a primary alopecia (Table 2). Additionally, in 36.4% (4 of 11) of primary AN cases, patches of alopecia were incorrectly managed or untreated for multiple years, due to diagnostic error, improper biopsy technique, or difficulty visualizing lesions through dense scalp hair. In cases of primary AN caused by malignant neoplasms, prompt diagnosis is critical to ensure best clinical outcomes. Despite low prevalence, the diagnosis is associated with high mortality and should be considered in patients presenting with a patch of scarring alopecia, particularly if unresponsive to treatments. We intend for this case report and literature review of primary AN to educate providers on benign and malignant primary scalp lesions masquerading as scarring alopecia.

Statement of Ethics

The subject provided written informed consent to publish this case and associated images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors did not receive any funding.

Author Contributions

Kelly E. Flanagan prepared the manuscript and gave final approval. Laura J. Burns prepared the manuscript and gave final approval. James T. Pathoulas provided revisions and gave final approval. Chloe J. Walker provided revisions and gave final approval. Isabel Pupo Wiss provided revisions and gave final approval. Kristine Cornejo, MD, provided histology images and written histologic descriptions, critical revisions, and final approval. Maryanne M. Senna, MD, was involved in conceptualization, critical revisions, image acquisition, project oversight, and final approval.