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. 2025 Nov 27;13(12):e71524. doi: 10.1002/ccr3.71524

Brooke–Spiegler Syndrome With Simultaneous Occurrence of Cylindroma, Spiradenoma, and Trichoepithelioma: A Rare Case With Malignant Progression

Parastou Gorovanchi 1, Mohammed Busehail 2, Ehsan Emami 3, Masooma Yaqoob 2, Mahsa Faramin Lashkarian 4, Nima Khalili 5, Nima Eftekhari 6, Sepideh Hadimaleki 7,8,✉, Bahareh Mehramouz 8,✉
PMCID: PMC12660013  PMID: 41321891

ABSTRACT

Brooke–Spiegler syndrome (BSS) is a rare autosomal dominant disorder characterized by multiple adnexal tumors. Malignant transformation is uncommon, and the simultaneous occurrence of cylindroma, spiradenoma, and trichoepithelioma with progression to basal cell carcinoma (BCC) has rarely been documented. A 73‐year‐old woman presented with multiple, painful nodules on the scalp, face, and periocular region that had been progressively increasing since puberty. She had a positive family history of similar lesions and a history of prior surgeries for recurrent tumors. Examination revealed multiple firm, erythematous nodules with post‐surgical scars. Histopathological analysis confirmed the coexistence of cylindroma, spiradenoma, and trichoepithelioma, with malignant transformation to BCC within one lesion. All accessible tumors were surgically excised, with no adjuvant therapy. No recurrence was observed at previously excised sites during follow‐up, but new lesions continued to develop in other areas. The disease caused significant cosmetic changes but no functional impairment. This case underscores the rare malignant transformation in BSS and emphasizes the need for lifelong dermatologic surveillance and early surgical intervention. Watchful follow‐up is critical to reduce morbidity and prevent complications from aggressive tumor behavior.

Keywords: adnexal tumors, basal cell carcinoma, Brooke–Spiegler syndrome, cylindroma, spiradenoma, trichoepithelioma

Key Clinical Message

Brooke–Spiegler syndrome can present with multiple adnexal tumors that may undergo malignant transformation. Lifelong dermatologic surveillance and timely surgical management are essential to detect malignant changes early and minimize morbidity associated with recurrent or aggressive lesions.

1. Introduction

Brooke–Spiegler syndrome (BSS; OMIM 605041) is a rare hereditary autosomal dominant condition marked by a susceptibility to the formation of numerous cutaneous adnexal tumors originating from the folliculo‐sebaceous‐apocrine unit [1, 2, 3]. The prevalent neoplasms linked to this syndrome include cylindromas, spiradenomas, spiradenocylindromas, and trichoepitheliomas (cribriform trichoblastoma) [4, 5]. These rare tumors, which develop around adolescence, primarily affect the scalp, face, and neck, and progressively evolve in both number and size over a lifetime [6, 7].

Malignant tumors develop in conjunction with preexisting benign cutaneous neoplasms in around 5%–10% of patients [8, 9, 10]. The gene associated with the disease's pathophysiology is the CYLD gene, a tumor suppressor gene situated on chromosome 16q12–q13 [11, 12, 13]. Besides the skin, morphologically analogous neoplasms may seldom develop in the salivary glands [8]. The occurrence of conjunction tumors (such as spiradenoma and cylindroma), carcinosarcomas, and cylindrocarcinomas, together with the simultaneous existence of basal cell carcinomas (BCC), has been documented [3, 14]. Surgical excision remains the mainstay of management for BSS‐associated adnexal tumors, although alternative modalities such as radiotherapy have been reported in selected inoperable or recurrent cases [15].

We present a rare case of BSS in which a patient simultaneously developed cylindroma, spiradenoma, and trichoepithelioma, three distinct benign adnexal tumors. This variant of the syndrome is particularly noteworthy due to the progression to BCC in the preexisting tumors.

2. Case Presentation

A 73‐year‐old female presented with multiple cutaneous lesions characterized by firm, elevated, and occasionally tender nodules involving the scalp (posterior to the ear), frontal, temporal, and periocular regions. The lesions initially appeared during puberty and gradually evolved in various regions of the face. Over the last two decades, she has endured several surgical excisions. The last excision's histological analysis identified many benign adnexal tumors, such as cylindroma, spiradenoma, and trichoepithelioma, with BCC developing within one of the previous lesions. No other therapies were provided except for surgical excision.

The patient disclosed a favorable familial history, including analogous lesions in her mother and son. Despite the absence of genetic testing, the clinical manifestations within her family clearly indicated BSS. The excised lesions measured approximately 0.5–1 cm in diameter, and primary closure was achieved without the need for flap repair.

3. Histopathological Observations

The histopathological analysis of the excised lesions verified the existence of several adnexal tumors, including cylindroma, spiradenoma, trichoepithelioma, and BCC, aligning with the diagnosis of BSS.

3.1. Trichoepithelioma

Samples from several lesions, including the scalp, left infraorbital, right periauricular, and left superior temporal areas, exhibited well‐defined dermal nodules consisting of basaloid epithelial cells organized in nests and cords. The nests had peripheral palisading, a distinctive feature of trichoepithelioma. Multiple horn cysts containing keratin were scattered across the tumor islands, encircled by a fibrocellular stroma. The histological characteristics were indicative of benign follicular differentiation (Figures 1, 2, 3, 4).

FIGURE 1.

FIGURE 1

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Scalp skin; Trichoepithelioma. Hematoxylin and eosin (H&E), ×100. Dermal nodule composed of basaloid epithelial cells arranged in nests and cords with peripheral palisading and keratin‐filled horn cysts surrounded by fibrocellular stroma.

FIGURE 2.

FIGURE 2

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Left infraorbital lesion; Trichoepithelioma. H&E, ×100. Multiple well‐circumscribed dermal nodules showing follicular differentiation with basaloid nests and scattered horn cysts.

FIGURE 3.

FIGURE 3

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Light periauricular lesion; Trichoepithelioma. H&E, ×200. Islands of basaloid cells with keratin horn cysts embedded in a fibroblastic stroma within the superficial dermis.

FIGURE 4.

FIGURE 4

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Left superior temporal lesion; Trichoepithelioma. H&E, ×200. Basaloid tumor nests displaying peripheral palisading and central keratinization, consistent with benign follicular differentiation.

3.2. Cylindroma

The excised lesion from the right temporal area had a distinctive jigsaw‐puzzle–like architecture, with islands of basaloid epithelial cells encircled by a dense, eosinophilic hyaline basement membrane. The tumor cells exhibited minor atypia, and mitotic figures were not conspicuous. The identified findings supported the diagnosis of cylindroma (Figure 5), a characteristic tumor linked to BSS.

FIGURE 5.

FIGURE 5

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Right temporal lesion; Cylindroma. H&E, ×100. Proliferation of basaloid cells forming jigsaw‐puzzle–like nests surrounded by thick, eosinophilic, hyaline basement membrane material in the dermis.

3.3. Spiradenoma

Histological slices of the middle frontal lesion exhibited well‐defined nodules consisting of two separate cellular populations: tiny basaloid cells with black nuclei at the periphery and larger, pale‐staining cells centrally located. The tumor had ductal differentiation, with many duct‐like structures distributed throughout the tumor lobules. Significant perivascular lymphocytic infiltration was seen, a characteristic hallmark of spiradenoma (Figure 6).

FIGURE 6.

FIGURE 6

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Middle frontal lesion; Spiradenoma. H&E, ×200. Well‐circumscribed dermal tumor composed of intermingled small basaloid cells and larger pale‐staining cells arranged in trabecular fashion, with prominent perivascular lymphocytic infiltration and dispersed hyaline material.

3.4. BCC Exhibiting Malignant Transformation

Two tumors in the right inferior temporal and left frontal areas exhibited characteristics indicative of BCC. The sections exhibited invasive nests of atypical basaloid cells entering the dermis, characterized by peripheral palisading and stromal retraction. In contrast to benign adnexal tumors, these lesions had heightened nuclear pleomorphism, hyperchromasia, and localized mitotic activity, indicating malignant development (Figures 7 and 8). The occurrence of BCC alongside several adnexal tumors generates apprehension regarding malignant transformation in a preexisting adnexal neoplasm, an uncommon although documented condition in BSS.

FIGURE 7.

FIGURE 7

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Right inferior temporal lesion; Basal cell carcinoma (BCC). H&E, ×200. Invasive nests of atypical basaloid cells with peripheral palisading, mild pleomorphism, and focal mitotic activity within a myxoid stroma.

FIGURE 8.

FIGURE 8

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Left frontal lesion; Basal cell carcinoma (BCC). H&E, ×200. Dermal infiltration by irregular cords of pleomorphic basaloid cells showing nuclear hyperchromasia and stromal retraction, indicating malignant transformation.

3.5. Outcome and Follow‐Up

Throughout her clinical course, the patient underwent multiple surgical excisions over the past two decades. Despite complete removal of the lesions at each procedure, new nodules continued to develop in different facial and scalp areas, consistent with the recurrent nature of BSS. The patient reported that the lesions had been present since puberty and had gradually increased in number and distribution with age. No systemic symptoms or functional impairments were observed, and she maintained normal daily activity. However, repeated surgeries resulted in visible postoperative scars on the scalp and face, leading to cosmetic concerns that significantly influenced her decision to seek further excisions.

Given the chronic and recurrent nature of her disease, the management approach remained primarily surgical, with no adjuvant therapy administered. At the most recent follow‐up, no recurrence was observed at the sites of prior excision, but new lesions of similar morphology were present in other areas. The development of BCC within a preexisting adnexal tumor highlights the potential for malignant transformation in chronic lesions. Because of this finding and the patient's age, regular long‐term dermatologic follow‐up was recommended to monitor for additional tumor formation or malignant behavior.

4. Discussion

BSS (OMIM code 605041) is characterized by the development of several cylindromas. This is an uncommon autosomal dominant condition initially characterized by Spiegler and Brooke [16, 17]. The condition is marked by the formation of adnexal tumors, primarily cylindromas, along with trichoepitheliomas and spiradenomas [3, 18]. Cylindromas often appear on the scalp, whereas trichoepitheliomas arise on the face, particularly in the perinasal region [19]. Lesions often develop during puberty or early adulthood and persist to grow throughout life. The condition primarily affects women. The documented male‐to‐female ratio is 1:6–9.6 [20].

BSS is presumably an underdiagnosed autosomal dominant genodermatosis, with varied but increasing penetrance with age (60%–100%), stemming from germline mutations in the CYLD gene located on chromosome 16q12‐q13 [4, 5]. These mutations are present in around 80%–85% of BSS patients [21]. Nonetheless, in the other instances, it is essential to consider the potential presence of de novo mutations in additional germline genes, modifications in noncoding areas, substantial chromosomal rearrangements or deletions, or other alterations not identified by standard sequencing methods [11, 12, 13].

Cylindromas are benign basaloid tumors that are painless and predominantly located in regions abundant in hair follicles and sebaceous glands. They normally emerge around adolescence, although they may occur earlier, develop slowly, and primarily afflict women, with a ratio of 6–9:1 [4, 22]. Clinically, they emerge as nodular erythematous lesions with overlaying telangiectasia and variable sizes, mostly located on the head, face, and neck. whereas the trunk, limbs, and pubic area are less involved [6, 22]. Multiple cylindromas may merge on the scalp, resulting in the formation of the turban tumor [4, 21, 22]. Malignant transformation of cylindromas may manifest with aggressive behavior in the context of BSS, marked by fast development, a pink‐blue hue, ulceration, and hemorrhage [6]. The dermatoscopic characteristics of cylindroma include prominent arborizing vessels at the periphery on a whitish‐pink background, blue spots and globules, as well as ulceration. These results resemble those found in the resected spiradenocylindromas of the proband. Cylindromas are histologically characterized as non‐encapsulated dermal nodules consisting of islands and cords of basaloid cells arranged in a jigsaw‐puzzle pattern, encircled by a robust, hyaline, PAS‐positive basement membrane. Epithelial cells in the perimeter of the islands have a propensity for palisading and are more pigmented than those situated in the center of the nodules [4, 23].

Spiradenomas often manifest as purple to bluish nodules of varying dimensions in almost any site and may be accompanied by paroxysmal pain. They frequently coexist alongside cylindromas, resulting in spiradenocylindromas, indicating a potential shared histogenesis [4, 21]. Histologically, spiradenomas are characterized by one or more distinctly defined large basophilic nodules within the dermis, occasionally extending into the subcutis. These nodules comprise trabeculae, sheets, cords, or islands featuring two predominant cell types: small epithelial basaloid cells with hyperchromatic nuclei at the periphery and larger cells with pale nuclei centrally located. Ductal structures are seen inside the lesions. Substantial spiradenomas may exhibit a hyaline stroma and vascular ectasia. In contrast to cylindromas, they may contain lymphocytes [4, 21, 23].

Trichoepitheliomas may potentially encompass the clinical range of BSS. They are benign tumors exhibiting follicular germinative differentiation. Trichoepitheliomas often present as skin‐colored papules on the midface, predominantly located on the nose and nasolabial folds [4, 22]. Microscopically, they comprise homogenous basaloid cells with peripheral palisading organized into nodules or nests of varying sizes, often exhibiting a cribriform pattern and core keratinization of the infundibular type. These cells are encased by a thick stroma including papillary mesenchymal structures [23]. Pinho et al. [24] reported two first‐degree relatives with reoccurring scalp erythematous telangiectatic nodules for decades despite many excisions. Lesion histopathology showed “spiradenocylindromas” in the proband and cylindromas in her sister. A new nonsense germline mutation of CYLD (c.1783C > T pGln 595*) in the proband confirmed BSS [24].

Malignant transformation in BSS is exceedingly uncommon but has been documented in several case reports, most frequently involving long‐standing cylindromas of the scalp. Slicinska et al. [25] described a 58‐year‐old lady sent for dermatological therapy for 30 years of scalp‐wide cutaneous cylindromas. One of the long‐lasting 5.5 cm lesions ulcerated in recent weeks, according to the patient. Ulcerating tumor histopathology showed cylindromas and basal cell cancer. Moreover, Kim et al. [26] described a 60‐year‐old man with a recurrent scalp cylindroma that underwent malignant change, requiring staged perimeter excision to achieve tumor‐free margins. Ho et al. [27] reported a similar case of carcinoma ex cylindroma in a patient with multiple BSS lesions, in which areas of benign cylindroma were contiguous with foci of cellular atypia, necrosis, and infiltrative growth. Merlo et al. [28] further documented a malignant eccrine spiradenocylindroma associated with parotid gland involvement, showing the potential for adnexal carcinomas in BSS to exhibit both local progression and extracutaneous extension. Altogether, these studies indicate that malignant evolution within BSS most often arises from a single tumor lineage, typically cylindroma or spiradenoma, and most likely presents as a rapidly enlarging, ulcerated, or hemorrhagic nodule after years of no to little growth.

In contrast, the present case demonstrates a broader and more complex disease phenotype. Our patient exhibited the concurrent presence of cylindroma, spiradenoma, and trichoepithelioma, followed by malignant transformation into BCC, a pattern rarely described in prior literature. Comparable benign combinations were observed in isolated cases reported by Leventer et al. [3] and Uede et al. [18], yet neither involved malignant progression. The emergence of BCC within this multifocal adnexal background suggests that malignant change in BSS is not restricted to traditional cylindroma or spiradenoma lineages and may reflect a wider field defect in follicular adnexal differentiation. This encourages the necessity of constant clinical and histopathologic observation, as even stable lesions may have malignant conversion over time.

5. Conclusion

This report describes an uncommon case of BSS characterized by the concurrent occurrence of cylindroma, spiradenoma, and trichoepithelioma, followed by malignant transformation into BCC. The present case highlights that malignant transformation, although infrequent, may arise in long‐standing adnexal tumors associated with BSS. Therefore, lifelong clinical surveillance and early surgical excision are essential to prevent disease progression and reduce morbidity. This case further underscores the importance of continuous clinical attention in patients with a prolonged history of multiple adnexal neoplasms. Additional investigations are warranted to elucidate the molecular mechanisms responsible for tumor transformation in BSS and to determine optimal management strategies for affected individuals.

Author Contributions

Ehsan Emami: conceptualization, data curation, writing – original draft, writing – review and editing. Mohammed Busehail: data curation. Parastou Gorovanchi: conceptualization, data curation, writing – original draft, writing – review and editing. Masooma Yaqoob: data curation. Mahsa Faramin Lashkarian: data curation, writing – original draft. Nima Khalili: data curation. Nima Eftekhari: data curation. Sepideh Hadimaleki: conceptualization, data curation. Bahareh Mehramouz: methodology, supervision.

Funding

The authors have nothing to report.

Disclosure

Consent to Participate: Written informed consent to participate was obtained from the patient in accordance with institutional policy. Consent for Publication: Written informed consent for publication of the clinical details and accompanying images was obtained from the patient.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

We sincerely thank the dermatology and pathology teams at Tabriz University of Medical Science for their assistance in patient care and specimen processing.

Gorovanchi P., Busehail M., Emami E., et al., “Brooke–Spiegler Syndrome With Simultaneous Occurrence of Cylindroma, Spiradenoma, and Trichoepithelioma: A Rare Case With Malignant Progression,” Clinical Case Reports 13, no. 12 (2025): e71524, 10.1002/ccr3.71524.

Parastou Gorovanchi, Mohammed Busehail, and Ehsan Emami are co‐first authors.

Contributor Information

Sepideh Hadimaleki, Email: sepidhadi74@gmail.com.

Bahareh Mehramouz, Email: mehramuzb@tbzmed.ac.ir.

Data Availability Statement

All relevant data supporting the conclusions of this case report are included within the article. De‐identified additional images or materials are available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

All relevant data supporting the conclusions of this case report are included within the article. De‐identified additional images or materials are available from the corresponding author upon reasonable request.

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