Shadow Cells Research Articles

Apocrine mixed tumor of the skin with a prominent pilomatricomal component

Pilomatrical differentiation within an apocrine mixed tumor (AMT) when present is only focal and has not been reported to be extensive. We herein report an AMT with prominent pilomatrical differentiation. A 47-year-old male presented with a 0.7 cm lesion on the right eyebrow. Histologic sections revealed, underneath a neurofibroma, a well-circumscribed tumor composed of nodules of branching epithelial elements and occasional keratinous cysts within a myxoid and lipomatous stroma. The ductal structures appeared to be composed of two layers of basophilic cuboidal cells and exhibited decapitation secretion. In approximately 50% of the tumor, eosinophilic ghost/shadow cells associated with a foreign body giant cell reaction formed a nodule resembling a pilomatricoma. Focally, columns of matrical cells were seen giving rise to shadow cells. Cytokeratin (CK) 5/6 and CK14 labeled the epithelial component. CK7, CK19 and Ber-EP4 labeled the ductal structures. Carcinoembryonic antigen and epithelial membrane antigen highlighted the luminal surface. S100 stained the stromal cells within the myxoid matrix, adipocytes and spindle cells within the overlying neurofibroma. CK10 highlighted the corneocytes within the keratinous cysts. CK17 labeled the epithelial lining of the keratinous cyst. The presence of follicular and apocrine differentiation within our tumor reinforces the common embryologic derivation of these elements.

Mutations in Exon 3 of the CTNNB1 Gene (β-Catenin Gene) in Cutaneous Adnexal Tumors

Previous studies suggested that mutant beta-catenin gene cells in cutaneous adnexal tumors with matrical differentiation contribute to their tumorigenesis. Except for pilomatricoma and pilomatrical carcinoma, only a handful of other cutaneous adnexal tumor types have been studied. DNA was extracted from 86 lesions including 17 proliferating tricholemmal and trichilemmal tumors, 15 trichoblastomas, 7 trichoadenomas, 4 pilomatricomas, 1 pilomatrical carcinoma, 4 basal cell carcinomas (BCCs) with shadow cells, 2 trichofolliculomas, 3 BCCs with sebaceous differentiation, 9 sebaceous adenomas, 6 sebaceomas, 14 sebaceous carcinomas (both ocular and extraocular forms), 2 gigantic horns, and 2 apocrine mixed tumors with shadow cells and subjected to polymerase chain reaction with newly designed primers encompassing glycogen synthase kinase-3beta phosphorylation sites of the CTNNB1 gene. Also, 3 craniopharyngiomas were studied. Sequenced polymerase chain reaction products for possible beta-catenin gene mutations showed a total of 8 alterations. These included 5 different point mutations, 3 of them identified in 2 different tumors: S23N (cribriform trichoblastoma), D32Y (pilomatricoma and craniopharyngioma), G34R (pilomatrical carcinoma and craniopharyngioma), S37F (2 BCCs with shadow cell differentiation), and G34V (craniopharyngioma). This study broadens the list of cutaneous adnexal tumors harboring CTNNB1 mutations and extends the listing of the mutations occurring in these neoplasms.

Pilomatrixom der okulären Adnexe: Klinische und histologische Aufarbeitung von 13 Fällen

Pilomatrixoma (calcifying epithelioma of Malherbe) is a rare benign tumour originating from the matrix of the hair root. In this study, we evaluated the clinical and histopathological characteristics of all the respective tumour specimens submitted to our laboratory since 1997. We reviewed the clinical and histologic findings of 13 pilomatrixomas localised to the ocular adnexae. Paraffin sections were stained with H&E and PAS and, in addition, immunohistochemistry was performed using markers for macrophages (CD68), for proliferative activity (Ki67), and for proliferation/apoptosis (CAS/CSE1L). All 13 pilomatrixomas were of reddish-livid colour and localised on the upper eyelid and/or near the eyebrow. The patients ages ranged from 4 to 84 years without preference for either gender. In 3 cases the correct diagnosis was made intraoperatively, while no pilomatrixoma was diagnosed prior to surgery. The most frequent false diagnoses were retention cyst (n = 3), atheroma (n = 2), and abscess (n = 2). There was no tumour recurrence in any of the cases within the time period presented. All 13 pilomatrixomas demonstrated the characteristic histology with areas of basophilic islands, shadow cells, calcification and a chronic granulomatous inflammation with foreign body giant cells in varying amounts. Immunhistochemical staining with anti-Ki67 and anti-CAS/CSE1L indicated a regular cellular maturation of the basophilic cells. No correlation was found between any of the histological or immunohistochemical markers and clinical parameters such as size, age and gender of the patient and duration of tumour presence prior to surgery. This case series represents one of the largest published so far, and underscores that pilomatrixoma can appear at any age. While it is usually not recognised clinically, it should be considered in the differential diagnosis especially for tumours of the upper eyelid. Our immunohistochemical findings support the basically benign nature of a pilomatrixoma but also point to the chronic inflammatory stimulus that can lead to complications after incomplete removal.

Immunohistochemical detection of Wnt/β‐catenin signaling, downstream effector molecules, and apoptosis‐related genes in an ossifying pilomatrixoma of cheek

ABSTRACTPilomatrixoma is an uncommon benign calcifying epithelial neoplasm derived from hair matrix cells, manifested as a firm intracutaneous spheroid mass on the face, neck, and arms, but its pathogenesis is still not clearly understood. This case study aimed to elucidate the downstream effector molecules and apoptotic processes through the Wnt/β‐catenin signaling in an ossifying pilomatrixoma. The histological analysis of whole tissue in this case showed the mixture of shadow and basophilic epithelial cells, where the shadow epithelial cells were most abundant in the superficial layer and the transitional epithelial cells were diffusely distributed between the shadow cells and basophilic cells. The basophilic epithelial cells usually distributed around the basal layer were intensely stained for Bcl‐2 and HSP‐70 antisera. The BMP‐2 was strongly condensed in the shadow cell and the osteoid matrix nearby. The transitional epithelial cells also formed the aberrant hair follicle, where the β‐catenin, APC, and TGase C were strongly localized. Especially, the β‐catenin and APC were clearly localized at the nuclei of the transitional epithelial cells, while E‐cadherin and Wnt‐1 were mainly expressed in the mesenchymal cells of underlying connective tissue. On the other hand, the immunostains of PCNA, p21, p53, Bax, TGase E, TGase K, and TUNEL stain were almost negative in the tumor epithelium. These findings suggest that the tumor cells of the ossifying pilomatrixoma are abnormally regulated for their cytodifferentiation and cellular apoptosis, resulted in the accumulation of the shadow epithelial cells, which produce the downstream effector molecules of Wnt/β‐catenin pathway, that is the osteogenic molecules of BMP‐2 enable to induce the bony tissue directly in the vicinity of the epithelium.

Metastatic malignant pilomatrixoma: a case report and review of the literature

Pilomatrixoma is a common benign adnexal tumour with differentiation towards matrix of the hair follicle. It is typically located in the head and neck region. The tumour is well circumscribed, lobular, cystic and composed of three major cell types: proliferating basaloid cells, eosinophilic squamous cells and shadow cells which represent dead cells. We report a rare case of malignant pilomatrixoma of the posterior occipital region in a 43-year-old female with metastases to C2 vertebra. The case was originally reported as proliferating pilomatrixoma. Bones of the head and neck region are a common site for metastases in malignant pilomatrixoma. Malignant pilomatrixoma is extremely rare. There are 90 cases regarded as acceptable reported in the English literature and ninety cases of metastasis. Because of its rarity, the precise incidence and prevalence of malignant pilomatrixoma are unknown. The diagnosis of malignancy is based on histological criteria which are not well defined and somewhat subjective. This includes cytological atypia, high mitotic activity with atypical mitosis, areas of confluent tumour necrosis, infiltrative growth pattern and vascular, lymphatic or perineural invasion.

Anetodermic pilomatricoma

A pilomatricoma, or Malherbe's calcifying epithelioma, is an uncommon tumor originating from hair matrix cells. It is clinically characterized by a solitary, firm nodule. As the skin overlying the pilomatricoma may change in color and texture, its clinical presentation can vary. We report an unusual case of pilomatricoma with associated anetoderma on the lower extremity of a 12-year-old girl. Histology revealed a thinned dermis replaced by myxomatous tissue between the surface and a deep-seated tumoral mass. This mass is formed of irregular islands of basaloid cells, shadow cells, calcified areas and discrete inflammatory and foreign-body reactions surrounding it. Anetodermic cutaneous changes may occur in pilomatricomas without histological evidence of triggering factors.

Anetodermic Variant of a Periorbital Pilomatricoma

Pilomatricoma usually presents as a solitary hard nodule located deep in the dermis. However, a variant termed anetodermic is often seen in the elderly. Instead of a hard nodule, a rapidly growing bullous lesion is seen. The authors report a 60-year-old man who presented with an erythematous bullous lesion at the left medial canthus. The lesion started as a small 3-mm papule and grew significantly to a 12-mm lesion in 5 weeks. Histopathologically, the tumor was composed of basophilic and keratinized shadow cells typical of pilomatricoma. Anetodermic changes could also be seen, represented by intralesional hemorrhage, dilated blood and lymphatic vessels, and disruption of dermal collagen fibers. The anetodermic variant of pilomatricoma was described in 1943 and accounts for only 2% of cases. Compression of vessels by the neoplastic process and peritumoral inflammatory infiltration are the proposed pathogenic mechanisms underlying the atypical findings.

An Unusual Composite Pilomatrix Carcinoma With Intralesional Melanocytes: Differential Diagnosis, Immunohistochemical Evaluation, and Review of the Literature

We report a case of an extremely rare histologic combination of pilomatrix or pilomatrical carcinoma with admixed melanocytes within the same tumor mass. Pilomatrix carcinoma is a neoplasm of low-grade malignancy that is characterized by a tendency for recurrence but low risk of metastasis. A 77-year-old male presented with a nodule on the bridge of the nose that was excised. Histologically, it was typified by asymmetry and poor circumscription, the presence of several variably sized and shaped basaloid aggregations, and surface ulceration. The tumors were composed of pleomorphic basaloid cells with prominent nucleoli and frequent mitoses (some of which were atypical) accompanied by central areas with keratotic material, shadow cells, and foci of necrosis. In addition, intermingled with the pilomatrix carcinoma, several easily identified pigmented cells with dendritic processes were present singly and as small aggregates. There was no atypia associated with the melanocytic component. Immunohistochemistry revealed the CK14 to be positive mainly within the keratinizing and the squamous epithelial elements of the tumor. The melanocytic component was strongly immunoreactive for S100, melanoma cocktail (HMB45 and Melan-A), and microphthalmia transcription factor. Pilomatrix carcinoma with melanocytes should be distinguished from the conventional pilomatrixoma with pigmentation, melanocytic matricoma, melanoma, and pigmented basal cell carcinoma with matrical differentiation. Clinicians and pathologists should be aware of the occurrence of pilomatrix carcinoma with melanocytes because of its potential for diagnosis as melanoma. This peculiar lesion recapitulates the intimate relationship existing between matrical epithelium and melanocytes in the embryonal hair follicle or in the anagen stage of the hair cycle. It is possible that sun damage played a role in stimulating migration of melanocytes among matrical cells in this case.

Multiple Pilomatrixomas Affecting the Eyelid and Face

A 3-year-old girl presented with a right upper eyelid mass. The lesion had a reddish appearance, was firm to palpation, and was fixed to underlying tissues. Fourteen months after the lesion was excised, a similar lesion was discovered on the left side of the nose and was also excised. Histopathologic examination of the excised tumors revealed variable basophilic hair matrix cells and sheets of nonviable eosinophilic shadow cells. Foci of dystrophic calcification were also seen in the necrotic tumor areas. The histopathologic findings were found to be consistent with pilomatrixoma. Results of limited clinical work-up of the child for Gardner's syndrome, sarcoidosis, and myotonic dystrophy were negative. Multiple periocular and facial pilomatrixomas can occur in children in the clinical absence of myotonic dystrophy, Gardner's syndrome, and sarcoidosis.

A study on 28 cases' operation to treat pilomatrixoma of the eyelids and eyebrows in children

目的 探讨儿童眼睑及眉弓钙化上皮瘤的临床、病理特点和手术方法.方法 回顾性分析经手术治疗的儿童眼睑及眉弓钙化上皮瘤28例(28眼).结果 男12例,女16例.均为单发.发现肿块的平均年龄2岁9个月(年龄范围5月～8岁);就诊平均年龄3岁8个月(年龄范围7月～12岁).均因发现眼睑及眉弓缓慢生长的皮下硬结就诊.瘤体位于上眼睑13例、下眼睑1例、眉弓14例.瘤体直径4～15 mm,平均直径7 mm.瘤细胞由影细胞与嗜碱性细胞组成.临床误诊率21.42%.术后无复发.结论 钙化上皮瘤临床特征为坚硬的缓慢生长的皮下小结,病理组织学特征有嗜碱性细胞与影细胞.最佳治疗是手术,分别采用不同的手术方法,手术效果良好。

Basal Cell Carcinoma With Matrical Differentiation: Expression of .-catenin and Osteopontin

Basal cell carcinoma with matrical differentiation is an extremely rare variant. To date, only 12 cases have been described in the literature. This tumor is a typical basal cell carcinoma with basaloid nests containing shadow cells identical to those of pilomatricoma and pilomatrical carcinoma. We present two additional cases and have investigated the immunoprofile of .-catenin and osteopontin with the aim of determining both their biological significance and possible diagnostic utility. The morphological and immunohistochemical features of these cases that we have found suggest that basal cell carcinomas with matrical differentiation belong to a spectrum of lesions deriving from hair follicles in which .-catenin plays an important role in the tumor development, differentiation, and behavior.

Giant Pilomatricoma

A 52-year-old man was examined for an ulcerated, rapidly growing reddish nodule. It was 5.5 cm high with an 11 x 6-cm base and located on the left clavicle. The lesion had been present for approximately 7 years, and the patient complained occasional burning and pain. Clinical differential diagnoses included cutaneous lymphoma, sarcoma, squamous cell carcinoma, and cutaneous metastasis. Histopathologic examination revealed a well-circumscribed tumor involving the whole dermis and the subcutis and composed of partially confluent aggregates of matrical cells admixed with eosinophilic cornified material containing shadow cells. In addition, multinucleated giant cells, areas of calcification and metaplastic ossification, edema, and hemorrhage were also observed. On the basis of histopathologic features, the diagnosis of pilomatricoma was made. Our report highlights an unusual clinical appearance of pilomatricoma that made us consider a variety of primary or secondary cutaneous neoplasms in its differential diagnosis.

Estudo clínico-patológico do pilomatrixoma palpebral: experiência no hospital universitário Prof. Edgard Santos

To report the experience with eyelid pilomatrixoma during 30 years in a university hospital. A review of the Ophthalmic Pathology Laboratory at the "Hospital Universitario Prof. Edgard Santos", was conducted to identify eyelid tumor cases from 1974 to 2004. After identification of pilomatrixoma cases, a chart review retrieved data regarding gender, age, duration of symptoms, gross aspect, anatomic localization and clinical diagnosis. The hematoxilin and eosin stained sections were reviewed. Of a total of 621 eyelid tumors, four (0.64%) were pilomatrixomas. Three patients were male. The mean age at diagnosis was 25 years (from 8 to 54). Mean duration of symptoms was 5 months (from 2 to 12). In three cases the lesion was located in the inferior lid. Only one patient had a correct clinical diagnosis. Two cases exhibited a pseudo-capsule on histology. The case with 12 months of history was composed mainly of shadow cells. Foreign body reaction was seen in all cases, calcification in only one. This is a very rare benign tumor of young patients. Due to its rarity and variable clinical presentation, clinical misdiagnosis is common.

Cell adhesion protein expression in melanocytic matricoma

Melanocytic matricoma is a rare neoplasm thought to recapitulate the hair follicle in anagen. The tumor forms a nodule in the dermis containing basaloid, intermediate and shadow cells admixed with pigmented melanocytes dispersed as single dendritic cells. Because cadherins and catenins are crucial in the development of hair tumors, we examined the expression of E(epithelial)-, P(placental)-, N(nerve)-cadherin and beta-catenin in a melanocytic matricoma. A 66-year-old Caucasian woman with a history of breast cancer presented with a pigmented nodule on the shoulder. Pathology revealed a melanocytic matricoma with S-100 and HMB45-positive melanocytes. E- and P-cadherin were localized at the cell membrane of basaloid and differentiating keratinocytes, and in melanocytes, recapitulating the anagen hair. Both cadherins were absent in shadow cells. N-cadherin was not expressed. Beta-catenin had a differential distribution, in the nucleus and cytoplasm of basaloid cells, but at the cell membrane in differentiating cells and negative in shadow cells, paralleling the expression of E- and P-cadherin. Our results support the previously hypothesized resemblance of the tumor to the hair bulb in anagen and suggest a transcriptional role of beta-catenin in the development of this rare neoplasm.

Melanocytic Matricoma: A Distinctive Clinicopathological Entity

Melanocytic matricoma is a rare recently reported entity. It usually presents as pigmented, dark-papular, crusted lesion on sun-damaged skin of adult patients. Histopathologically, these lesions consist of well-circumscribed nodules with groups of “shadow cells” or “ghost cells” (matrical/supramatrical cells) and prominent pigmented dendritic melanocytes. It differs from matricomas and pilomatricomas by its lack of calcification, cyst formation, granulomas, and connections to the epidermis and other adnexal structures. The clinical differential diagnosis includes hemangioma, pigmented basal cell carcinoma, and melanoma. Melanocytic matricoma presumably is the representation of an epithelial-melanocytic interaction in the anagen phase of the hair cycle, and the melanization is due to normal melanocytes colonizing a neoplastic proliferation. A extensive search of the medical literature revealed 5 reports of benign melanocytic matricomas and 2 malignant counterparts. We present 2 additional cases of melanocytic matricoma with clinicopathologic correlation. The first case is from the dorsum of the hand of a 70-year-old white male and the second from the preauricular area of an 82-year-old white male, both with prior history of skin cancer. The small size, well-circumscribed appearance, and the symptom-free nature signifies benignity. However, if cytologic atypia is present, it is indicative of malignant behavior. Correct interpretation of melanocytic matricoma is extremely important due to its clinical and histopathologic overlap with other more ominous lesions.

Pilomatricoma of the Maxillofacial Area in the Northern Regional Jordanian Population: Report of 31 Cases

To analyze the clinicopathologic features of pilomatricoma affecting the maxillofacial area in Jordanians. Records of the Department of Pathology at Jordan University of Science and Technology were reviewed for patients with biopsied pilomatricoma of the maxillofacial region received during the 11-year period extending between 1991 and 2001. These were retrieved, reviewed, and analyzed for age, gender, location, clinical features, and treatment. There were 31 cases with an age range from 4 to 48 years (mean, 16.7). The majority (74%) of patients were in their first (45%) and second (29%) decades of life with a male to female ratio of 1 to 1.4. The periorbital (36%), the periauricular (28%), and the upper cervical region (23%) were the affected areas. The majority of cases presented as a painless skin nodule with a duration varying from 2 months to 3 years. The majority (97%) of tumors were between 0.5 cm and 2 cm in diameter. Histologically, almost 50% of tumors showed shadow cells alone. All tumors were removed surgically. The clinicopathologic characteristics of pilomatricoma of the maxillofacial area in Jordanians are similar generally to those in other countries. Maxillofacial surgeons need to be more aware of this lesion and should consider it in the differential diagnosis of dermal masses they encounter.

Intraosseous pilomatricoma: a possible rare skeletal manifestation of Gardner syndrome

Here we report a case of intraosseous pilomatricoma in a patient with Gardner syndrome. A 17-year-old boy with a family history of Gardner syndrome and multiple cutaneous epidermoid cysts presented with pain in the region below the knee of the left leg. Plain radiographs displayed a well-circumscribed eccentric lesion of mixed radiolucent and radiopaque density within the diaphysis of the left proximal tibia. By magnetic resonance (MR) imaging, the lesion appeared as a low intensity lesion in T1-weighted images and a heterogeneous high intensity lesion with a low-signal radiation pattern on T2-weighted images. Gadolinium enhancement was observed partially within the lesion and intensely in the lesion rim. After curettage, histological examination revealed a massive accumulation of keratinous material with epithelial nests that displayed both epidermal and trichilemmal keratinization with basaloid and shadow cells and with metaplastic ossification. These features confirmed a pathological diagnosis of intraosseous counterpart of pilomatricoma. In the context of this patient's skin lesions, intraosseous pilomatricoma may be a rare skeletal manifestation of Gardner syndrome.

著明な石灰化と骨形成を伴った石灰化上皮腫の１例

Calcifying epithelioma (pilomatrixoma) is a benign cutaneous tumor derived from skin appendages, such as pilomatrix. It is usually a solitary tumor and commonly found on the head, neck, and upper extremities inyoung-adult women; multiple occurrences are rare. Histopathologically, the tumor is composed of basophilic cellsand eoshinophilic shadow cells with occasional calcification and bone formation.A 20-year-old woman presented to our clinic with a 4-year history of amass arising in the inferior part of theright auricle. Examinations revealed two other solitary masses on both forearms. The tumor at the inferior part ofthe auricle showed marked calcification and ossification. We also clinicopathologically compared this case withfive previous cases. Wound healing was good 1 year and 6 months after surgery.

Follicular Germinative Cells in Pilomatricoma

Pilomatricoma is a follicular neoplasm that shows differentiation towards the follicular matrix, as characterized by matrical cells and shadow cells. In addition, this is sometimes accompanied by differentiation toward the follicular infundibulum and outer root sheath. These finding suggest that pilomatricoma can subtly differentiate towards any structure of the follicle. However, morphologically, no distinct germinative cells resembling embryonic follicular germ cells have been found in pilomatricoma to date. We report on two cases of pilomatricoma in which distinctive follicular germinative cells palisaded at the edges of collections of matrical cells. We propose two explanations: one is that the metrical cells of pilomatricoma can focally de-differentiate to form follicular germinative cells, and the other is that these follicular germinative cells are the precursor cells of pilomatricoma.

Pilomatricomal Horn

We describe a pilomatricomal horn on the right arm of a 39-year-old man. Although initially the tumor was clinically thought to be a verruca vulgaris, the microscopic features were similar to those found in classic pilomatricoma, except for the epidermal location and the presence of a cutaneous horn. Light microscopy showed replacement of the epidermis by basaloid cells, with masses of cornified material containing shadow cells that formed a cutaneous horn. Whereas classic pilomatricoma is confined to the deep reticular dermis or subcutis, the present case represents a unique heretofore unreported epidermal variant of pilomatricoma that pathologists should be aware of to differentiate it from malignant epidermal tumors.