Does endometrial morular metaplasia represent odontogenic differentiation?

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear ß-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for ß-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the ß-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant parotid gland tumor.

BACKGROUND: Pilomatricoma is a relatively common benign cutaneous adnexal neoplasm with differentiation towards the hair matrix, inner sheath of hair follicle and hair cortex. Proliferating pilomatricoma is a rare variant of pilomatricoma that can rapidly increase and may be misidentified as a malignant tumor. We herein report the cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant parotid tumor. CASE PRESENTATION: A 64-year-old man noticed an acne-like nodule in the left parotid region. It was painless, but it increased to a maximum diameter of 4.5 cm over 2 years. Clinically, left parotid gland carcinoma was suspected, and fine-needle aspiration cytology was performed. Clusters of epithelial cells were observed in a necrotic background, and malignant epithelial cells derived from salivary glands were suspected. Histologically, the resected tumor was diagnosed as proliferating pilomatricoma composed of basophilic cells and shadow cells apart from the parotid gland. However, on a re-evaluation of the cytological specimens, the irregular-shaped epithelial cells were considered to be from basophilic cells. Shadow cells with nuclear disappearance were also confirmed. Tumor recurrence and metastasis have not been observed in the four years since surgery. CONCLUSION: The present case was first interpreted as a malignant parotid gland tumor, but it was actually a benign skin appendage tumor. Pilomatricoma sometimes rapidly increases and may be mistaken for a malignant tumor. Although it is critical to recognize not only basophilic cells but also shadow cells, it cannot be diagnosed by cytological findings. The final diagnosis should be made on excision specimen only.

Malignant Melanocytic Matricoma: A Report of 2 Cases and Review of the Literature.

BACKGROUND: To describe 2 cases of melanocytic matricoma with malignant histological features and systematically review previously reported cases of malignant melanocytic matricoma. METHODS: Two cases of malignant melanocytic matricoma were identified from the practice of the authors. Additional 3 cases were identified in the literature. The clinical and pathological features of these 5 cases are described. RESULTS: Malignant melanocytic matricoma occurs predominantly in sun-damaged skin of elderly individuals. The tumor is composed of atypical epithelial cells with brisk mitotic activity showing evidence of matrical keratinization and widespread positivity with beta-catenin. There is an admixed cytologically bland dendritic melanocytic component. To date, local recurrence has occurred in one case, but no cases of disseminated disease or death have been reported. CONCLUSIONS: Recognition of this rare tumor and separation from a range of diagnostic mimics is important to ensure adequate treatment by local excision and to allow further cases to be identified to better define the biological potential of this lesion.

Matrical Carcinoma With Melanocytic Proliferation and Prominent Squamoid Whorls.

Matrical carcinoma (pilomatrix carcinoma) is a rare follicular low-grade malignancy with matrical differentiation. A pigmented variant with admixed dendritic melanocytes is exceedingly rare with only 7 cases reported in the literature. The diagnosis of malignancy can be difficult to establish. The authors report a case of a 79-year-old woman with a matrical carcinoma who presented with an ulcerated nodule on the posterior right leg, measuring 2.2 cm in greatest dimension. The excisional biopsy showed irregularly shaped dermal and subcutaneous nodules ranging in size from 0.1 to 0.5 cm. The nodules were composed of aggregates of large atypical basaloid cells, with multiple, sometimes atypical, mitoses, admixed with ghost cells, and central necrosis en masse. In addition, the neoplasm was characterized by focal marked melanocytic proliferation and multiple whorls of pink eosinophilic material reminiscent of keratin pearls (squamoid whorls). The basaloid cells were positive for beta-catenin both in the nuclei and the cytoplasm and negative for BerEp4. S100, Melan-A, and HMB45 highlighted the melanocytic dendritic cells. Pan-cytokeratin was negative in the ghost cells and focally positive in the squamoid whorls. Squamoid whorls seem to be a significant feature of matrical carcinoma.

Pigmented pilomatricoma: an underrecognized variant.

The presence of melanin pigment and/or melanocytes in pilomatricoma has been rarely documented. In this study, we analyzed the incidence and clinicopathological features of pigmented pilomatricoma. Fifty-seven consecutive pilomatricoma cases from 53 Japanese patients were examined in this study. In fourteen cases (24.6%), pigmentation was observed in pilomatricoma. This variant equally affected in males and females, and the common locations were the upper arm and face. Proliferation of dendritic melanocytes was observed within basaloid cell nests in all cases, and melanin pigment was also present within the cytoplasm of the basaloid cells in 11 cases. Melanin pigment was also present in the shadow cells in 7 cases. The incidence of pigmented pilomatricoma as documented in previous reports is approximately 10%. However, our analysis revealed that pigmented pilomatricoma was found in 24.6% of Japanese cases of pilomatricoma, thus, this variant is not uncommon and may be under-recognized.

Cutaneous hybrid tumor composed of epidermal cyst and cystic pilomatricoma expressing p53 and high Ki-67 labeling.

Hybrid tumor composed of epidermal cyst and pilomatricoma has been reported in only four times in the English literature. Herein, a cutaneous hybrid tumor composed of epidermal cyst and cystic pilomatricoma in a 58-year-old woman was presented. The tumor was located in the scalp, and measured 1 x 1 x 1 cm. The tumor was cystic and contained atheromatous materials. Histologically, the cyst was composed of epidermal cyst (50% in area) and pilomatricoma (50% in area). The pilomatricoma was composed mostly of basophilic cells. Interestingly, the pilomatricoma element of the cyst showed immunoreactive p53 and Ki-67 (labeling=40%). In conclusion, the fifth case of hybrid tumor composed of epidermal cyst and pilomatricoma was presented.

Anetodermic pilomatricoma: molecular characteristics and trauma in the development of its bullous appearance.

Pilomatricoma is a common benign neoplasm of the skin characterized by a solid cutaneous nodule of hair matrix origin. The anetodermal or lymphangiectatic variant of pilomatricoma is rare, and its bullous appearance is often associated with attenuated collagen and elastic fibrils and dilated lymphatic vessels in the overlying dermis. However, the tumors of anetodermic pilomatricoma have never been characterized at the molecular level, and the exact mechanism for their development is unknown. In this study, we evaluated histological and molecular features of a bullous pilomatricoma along with 5 control tumors and determined that tumors of both anetodermic and control pilomatricoma comprise similar molecular features, such as nuclear lymphoid enhancer binding factor 1 (LEF1) localization and the expression of keratins. In addition, we associated the development of the anetodermic pilomatricoma with mechanical trauma, scar tissue formation, and increased numbers of blood and lymphatic vessels. This study suggests that the development of the anetodermic form of pilomatricoma is unlikely to be associated with the intrinsic properties of the tumor but with the mechanical trauma that disrupts the dermal integrity and vascular microenvironment.

Where pigmented pilomatricoma and melanocytic matricoma collide.

Pilomatricoma and matricoma are 2 benign epithelial tumours derived from the hair matrix. Although containing the same constituent cells, the silhouette differs, with matricoma comprised of a predominantly solid basaloid proliferation with only focal areas of shadow cell formation. The recently described melanocytic matricoma appears to be a similar tumor with numerous interspersed melanocytes. We studied retrospectively 28 pilomatricomas and 2 pilomatrical carcinomas to check for the presence of melanocytes using immunohistochemical staining to S-100 and Melan-A. Three cases of pilomatricoma with prominent melanocytic hyperplasia were detected, confirming this as a rare (11%) occurrence. Both cases of pilomatrical carcinoma were negative. Comparison of these tumors with a further case of melanocytic matricoma led to a critical analysis of the relationship of pilomatricoma, matricoma, and melanocytic matricoma. Although further comparison is required, we suggest that melanocytic matricoma may be simply a pigmented melanocytic variant of matricoma, in the same way as we accept pigmented pilomatricoma as a variant of pilomatricoma. In this report we provide features that may be used to discriminate matricoma and pilomatricoma and their pigmented variants.

Malignant transformation within benign adnexal skin tumours.

AIMS: To report five malignant trichogenic tumours arising in longstanding, previously benign adnexal neoplasms through malignant transformation. Malignant trichogenic adnexal tumours are extremely rare neoplasms. METHODS AND RESULTS: The patients were between 55 years and 79 years of age. Three of the tumours were located on the arms, two on the face. Three of our patients had a history of chronic lymphocytic leukaemia, one patient had a history of colonic adenocarcinoma. The duration of the tumour nodules was reported as between 20 and 40 years before sudden changes occurred. These changes included rapid growth, pain, itching, ulceration and bleeding. Histologically, all tumours were well circumscribed and encapsulated. There was a residual benign tumour component and morphological signs such as bone formation, dystrophic calcification and sclerosis suggesting long duration of the lesions. All patients except for one, who refused further clinical investigation due to her advanced age of 79 years, had an underlying systemic malignancy. CONCLUSIONS: The growth stimulus in these benign adnexal neoplasms resulting in malignant transformation may be attributed to the acquisition of additional genetic events or to immunosuppression due to an underlying neoplastic disease. Therefore, patients with systemic diseases or malignancy should be carefully examined and followed for sudden changes in pre-existing benign cutaneous tumours.

beta-Catenin is expressed aberrantly in tumors expressing shadow cells. Pilomatricoma, craniopharyngioma, and calcifying odontogenic cyst.

We studied the beta-catenin immunohistochemical profile in tumors expressing shadow cells: pilomatricoma, 10 cases; calcifying odontogenic cyst, 6 cases; and craniopharyngioma, 9 cases. There was strong membranous, cytoplasmic, and nuclear staining of the immature basaloid cells in all of these tumors. Shadow cells were negative in all tumors. It has been documented that rising levels of free beta-catenin drive the formation of complexes with T-cell factor/lymphoid enhancer factor (TCF-Lef) and up-regulate the wingless-Wnt cell-cell signals. The end result is an abnormality of beta-catenin degradation and, thus, a buildup of free beta-catenin in the cytoplasm and/or nucleus, resulting in the stimulation of cellular proliferation and/or inhibition of cell death. beta-Catenin seems to have an important role in the oncogenesis of these tumors. The similar pattern of keratinization in these tumors and the similar pattern of beta-catenin immunoreactivity in the cytoplasm and the nucleus are important findings. It seems that the activation of a common cellular pathway, namely Wnt-beta-catenin-TCF-Lef, has a role in the pathogenesis of these tumors. The latter could be related to their shared method of keratinization or shared dysfunction of the cellular adhesion complex leading to tumorigenesis.

Matrical carcinoma with prominent melanocytic hyperplasia (malignant melanocytic matricoma?) A report of two cases.

Melanocytic matricoma is a recently described lesion characterized by well-circumscribed nodules composed of matrical and supramatrical cells with clustered ghost cells, and admixed pigmented dendritic melanocytes, with no cyst formation or connection to the epidermis or pre-existing hair follicles. Although variable cytologic atypia and frequent mitoses in the epithelial component may be present, given the well-defined margins and absence of tumor recurrences, these lesions were initially considered benign neoplasms, and not matrical carcinoma. Theoretically, the detection of numerous melanocytes in matrical carcinoma should not be surprising, but is in fact a very unusual feature. A case with extensive melanization of epithelial elements and only rare melanocytes has been reported. We report two cases of matrical carcinoma with prominent melanocytic hyperplasia, with emphasis on the ultrastructural and immunohistochemical features. Our cases might be considered the malignant counterpart of the so-called melanocytic matricoma.

Melanocytic matricoma: a report of two cases of a new entity.

Many reports exist of pigmented adnexal tumors containing dendritic melanocytes such as pigmented basal cell carcinomas and pigmented pilomatricomas. Correspondingly, melanocytes are a known component of the bulbs of anagen follicles. The phenomenon of melanization of adnexal tumors highlights the interrelationship between melanocytes and adnexal epithelium and may represent normal melanocytes colonizing a neoplastic proliferation. We report on two cases of a unique tumor composed of neoplastic matrical cells with a significant component of melanocytes. Both cases presented as pigmented papules in older men (66 and 80 years, forearm and pectoral region, respectively). Histologically, these were well-defined nodular proliferations composed of variably melanized, pleomorphic, and mitotically active matrical and supramatrical cells forming clusters of "shadow cells." Admixed with the epithelial cells were numerous melanized dendritic melanocytes. Shadow cells expressed keratin 13, and a subpopulation of S-100 protein-positive dendritic cells were evident. No recurrence of any type was found after reexcisions 4 months and 2 years later. We propose the name of melanocytic matricoma for these two heretofore unreported cases of a unique neoplasm composed of matrical cells and melanocytes recapitulating epithelial-melanocyte interaction in the follicular anagen bulb. Although their small size, circumscription and clinical course suggest a benign nature, melanocytic matricomas' cytologic atypia disclose the potential for malignant behavior.

A reappraisal on the modes of cell death in pilomatricoma.

The modes of cell death in pilomatricoma were analysed using 27 nodules. The shadow cells with lost nuclei and preserved cytoplasms were morphologically considered to be derived from basaloid cells via transitional cells, which showed gradual loss of nucleic acid by Feulgen reaction and methylgreen-pyronin stain and no nuclear fragmentation. This process was regarded as cell death associated with terminal differentiation into hair. Amorphous debris among the shadow cells contained many fragmented nuclei (apoptotic bodies), which were directly derived from basaloid cell layer focally undergoing apoptosis and did not have any transition to transitional cells. Although in situ 3'-tailing reaction for a detection of dying cells labelled both transitional cells and apoptotic bodies in the amorphous debris, these two components were considered to be on different histogenetic pathways. Immunostainings for the Bcl-2 family revealed no expression of Bax, Bad or Bak protein in any components, whereas Bcl-2 protein was detected in the periphery of basaloid cell layer, but not in the transitional or shadow cells. These results indicate that there are two different modes of cell death in pilomatricoma: i) terminal differentiation into shadow cells; and ii) conventional apoptosis observed as amorphous debris.

Proliferating pilomatricoma. A histopathologic simulator of matrical carcinoma.

We report on 9 patients with pilomatricomas that showed unusual histopathologic features. Our patients were mainly elderly individuals (age range 42 to 88 years; mean age 70.1 years) who presented solitary cutaneous nodules situated on the head and neck (7 neoplasms), upper arm (1 neoplasm), and back (1 neoplasm). All the lesions were treated by simple excision. Follow-up data available in 7 of the 9 patients (mean follow-up, 17 months) revealed local recurrences in 1 patient whose lesion recurred 3 times. No lymph node involvement or distant metastases were recorded in any of our cases. Histopathologically, most neoplasms were characterized by a relatively large lesion in the dermis that in some cases showed extension to the subcutis. Each lesion was predominantly composed of a lobular proliferation of basaloid cells in association with adjacent focal areas containing eosinophilic, cornified material with shadow cells. In some cases, relatively large areas of shadow cells were present, whereas, in others only small foci of shadows cells were observed. Cytomorphologically, the basaloid cells showed features of matrical and supramatrical cells of a normal hair follicle and exhibited variable nuclear atypia and mitotic figures. The overall architectural pattern of the neoplasms was different from that of large fully developed stereotypical pilomatricomas that maintain a cystic character with basaloid cells predominantly aligned at the periphery. Based on the histopathologic findings, namely the presence of a large, lobular proliferation of basaloid cells in association with small to large foci of shadow cells, we interpreted these neoplasms to be a distinctive proliferative variant of pilomatricoma and propose the designation "proliferating pilomatricoma." Proliferating pilomatricomas should be differentiated from the recently described matricoma, basal-cell carcinoma with matrical differentiation, and matrical carcinoma (pilomatrical carcinoma).

Immunohistochemical localization of cytokeratins and involucrin in calcifying epithelioma: comparative studies with normal skin.

The expression of cytokeratins and involucrin varies greatly in different epithelia, and this raises the possibility that detailed analysis of these epidermal proteins might provide a means of identifying various skin tumours. The present study was conducted to determine the immunohistochemical distribution of cytokeratins and involucrin in calcifying epithelioma of Malherbe, in order to elucidate the nature and differentiation of this tumour. To correlate the immunohistochemical profile with the most frequent histological patterns, we categorized the basophilic, transitional, shadow, and squamoid cells, and the shreds of keratin. Comparative studies with normal skin showed that the shadow and transitional cells corresponded to hair cortex cells, the squamoid cells to the outer root sheath, the basophilic cells adjacent to the stroma to the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the follicles, and the basophilic cells adjacent to the transitional cells to the hair matrix. The expression of cytokeratins in most shreds of keratin was similar to that in squamoid cells. Calcifying epithelioma was, therefore, shown to be composed of tumour cells differentiating into both the hair cortex and outer root sheath. These tumour cells were differentiated from basophilic cells, which showed the same staining patterns as the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the hair follicles, supporting the hypothesis that the keratinocytes in the outermost cell layer can differentiate into the transitional portion of the follicle and anagen hair.