Sebaceous Gland Carcinoma Research Articles

Deletions of BRCA1/2 and p53 R248W gain-of-function mutation suggest impaired homologous recombination repair in fragile histidine triad-negative sebaceous gland carcinomas

Sebaceous gland carcinomas represent rare malignancies of the skin and some 60% of them demonstrate high-grade microsatellite instability on the background of a defective mismatch repair system. However, a significant fraction of periocular sebaceous gland carcinomas exhibits microsatellite stability associated with a frequent loss of the candidate tumour suppressor fragile histidine triad (FHIT). We hypothesized that in those sebaceous gland carcinomas with microsatellite stability and loss of FHIT, effector molecules participating in homologous recombination repair (HRR), such as BRCA1/2, could be somatically inactivated. A pilot series of 10 paraffin-embedded sebaceous gland carcinoma specimens with a defined FHIT status was studied for loss of heterozygosity (LOH) events in the genes BRCA1, BRCA2, FHIT and WWOX. We sequenced the coding exons 5-8 of the p53 gene. Sebaceous gland carcinomas with FHIT negativity displayed LOH and biallelic deletions of the BRCA1 gene in five of 10 (50%) of the sebaceous gland carcinoma specimens analysed. Tumour-specific genomic losses close to BRCA2 were also uncovered. A homozygous p53 R248W gain-of-function mutation as the result of a CGG to TGG transition was identified in one of seven sebaceous gland carcinomas. It has been demonstrated previously that p53 R248W mutants inactivate ATM-directed HRR. This particular sebaceous gland carcinoma presented with concomitant genomic deletions at the BRCA1 and BRCA2 loci, and also at the constitutively fragile sites FRA3B/FHIT and FRA16D/WWOX. Our study demonstrates for the first time that microsatellite-stable FHIT-negative sebaceous gland carcinomas accumulate mutations that target central components of the HRR network. This observation will prompt investigations in synthetic lethality of BRCA-deficient sebaceous gland carcinomas by therapeutic poly(ADP-ribose) polymerase inhibitors.

Eyelid Sebaceous Gland Carcinoma in a Young Caucasian Man

Eyelid sebaceous gland carcinoma is rarely observed in young Caucasian men. A 28-year-old man was referred for a recurring chalazion of the eyelid that had been operated four times in the past two years. The chalazion-like lesion of the external third of the upper left eyelid was associated with a cystic lesion. Cytology of the fluid in the cyst and histology of the lesion were compatible with a sebaceous cell carcinoma. Magnetic resonance imaging revealed that the cystic lesion associated with the eyelid tumour was extending into the orbit. According to current clinical practice and experience, to increase the chance of survival of the patient, an orbital exenteration was conducted to remove the sebaceous cell carcinoma in total. Although rare, one should be aware that an eyelid sebaceous cell carcinoma can occur in a young Caucasian man and this diagnosis should be evoked in case of a recurrent chalazion.

Clinical and pathological analysis of 2639 cases of eyelid tumors

To describe the histopathologic spectrum and patient characteristics of eyelid tumors in Beijing Tongren Hospital. It was a claims database analysis. A total of 2639 eyelid tumors verified histopathologically from January 1997 to December 2006 were included in the study. Of the 2639 eyelid tumors, the 5 most common eyelid benign lesions were inflammatory lesion, melanocytic nevus, papilloma, dermoid cyst and epidermoid cyst, and epithelial cyst. The 5 leading eyelid malignant tumors were basal cell carcinoma, sebaceous gland carcinoma, lymphoma, squamous cell carcinoma and melanoma. The mean age at diagnosis was 61 years for basal cell carcinoma and sebaceous gland carcinoma, 57 years and 52 years for squamous cell carcinoma and melanoma, respectively, and 48 years for lymphoma. There was no significant sex predilection in basal cell carcinoma and sebaceous gland carcinoma. Melanoma and lymphoma occurred more commonly in women, whereas squamous cell carcinoma occurred more commonly in men. Basal cell carcinoma and sebaceous gland carcinoma were the most common malignant eyelid tumors, and lymphoma ranked third and had an increasing trend. The malignant tumors occurred predominantly in the elderly of 60 years and above.

Eyelid Neoplasms in the Beijing Tongren Eye Centre Between 1997 and 2006

To examine the spectrum of eyelid neoplastic specimens obtained at the Beijing Tongren Eye Centre between 1997 and 2006. A total of 2,639 eyelid neoplasms were included in the study. Of the 2,639 eyelid specimens, 2,276 (86.2%) were benign and 363 (13.8%) were malignant. The most common benign lesions were inflammatory lesions, melanocytic nevi, papillomas, dermoid and epidermoid cysts, and epithelial cysts. The most common malignant or semi-malignant tumors were basal cell carcinomas, sebaceous gland carcinomas, lymphomas, squamous cell carcinomas, and malignant melanomas. The mean age at diagnosis was 41 years for benign lesions and 60 years for malignant tumors. There was no significant gender predilection among the five major non-benign eyelid tumors. At the BeijingTongren Eye Centre between 1997 and 2006, the predominant non-benign eyelid tumors were basal cell carcinoma and sebaceous gland carcinoma, followed by lymphoma. The non-benign lesions occurred predominantly in elderly patients who were 60 years of age and older.

Cytohistological study of eyelid lesions and pitfalls in fine needle aspiration cytology

<b>Aims</b> : The purpose of the study was to evaluate different eyelid lesions appearing as a swelling or mass, using fine needle aspiration cytology (FNAC), to conduct a cytological diagnosis of these lesions with subsequent histopathological correlation, and to identify the problems faced during microscopical examination of the smears. <br><b> Materials and Methods</b> : Fine needle aspirates from 80 eyelid swellings and histopathological correlation in 62 cases were studied. <br><b> Results: </b> Forty eight cases of benign and 32 cases of malignant lesions were diagnosed by FNAC. The five leading benign lesions were chalazions (12 cases, 15%), epithelial cysts (eight cases, 10%), chronic nonspecific inflammation (six cases, 7.5%), seborrheic keratosis (five cases, 6.25%) and benign adnexal adenoma (four cases, 5%). The most common malignant lesion was basal cell carcinoma (12 cases, 15%) followed by sebaceous gland carcinoma (nine cases, 11.25%) and squamous cell carcinoma (eight cases, 10%). <br><b> Conclusions:</b> Histopathological correlation showed that the accuracy of fine needle aspiration cytology in making diagnosis was 83.87%. Incidence of basal cell carcinoma in the study was lower, compared to most western studies. Therefore, there may be a racial and geographical variation.

Clinical Features and Management of Eyelid Sebaceous Gland Carcinoma

Purpose: To investigate the clinical features and treatment results in eyelid sebaceous gland carcinoma. Methods: A retrospective chart review was conducted on 28 adult patients that were histopathologically diagnosed with eyelid sebaceous gland carcinomas from April 1981 to March 2005 in Seoul National University Hospital. Results: Among the 28 cases of eyelid sebaceous gland carcinoma, 9 cases (32.1%) had evidences of local invasion or metastasis at the initial diagnosis. Surgical resection was performed in the 27 cases (96.4%), and conjunctival cryotherapy, surgeries, such as maxillectomy, parotidectomy, and neck dissection, or radiation therapy were combined in cases of local invasion or metastasis. In the 19 cases of the localized tumor group, there were 2 cases (10.5%) of recurrence after an average 30 months of follow-up. The locally invasive tumor group (2 cases) showed 1 case of recurrence after 12 months of follow-up. In the 7 cases of the distant metastasis tumor group, tumors in 3 cases (42.9%) could not be controlled, and 3 cases (75.0%) showed recurrence after an average 45 months of follow-up. Conclusions: Eyelid sebaceous gland carcinomas with local invasion or metastasis afford higher potential for treatment failure, so early diagnosis is crucial. Because recurrence is possible, even when the tumor is completely removed, the extent of the tumor should be examined thoroughly and microscopically.

Clinicopathological Analysis of Periocular Sebaceous Gland Carcinoma

Background: We analyzed the clinicopathological features and prognosis in patients with periocular sebaceous gland carcinoma. Methods: Retrospectively, we studied the records of 24 cases of sebaceous gland carcinoma treated in our clinic between 1999 and 2004. The reviewed data included demographic information, initial clinical and histopathological diagnosis, anatomic tumor location, details of treatment, tumor involvement of resection margin, and outcomes such as local recurrence, distant metastasis and survival. Results: Local recurrence developed in 6 cases (25%) at a median of 20 months from initial diagnosis. Only 2 patients (8.3%) died of systemic metastasis to brain and bone from primary lacrimal gland carcinoma. The local recurrence rate in the complete excision group (5.9%) was significantly lower compared with the incomplete excision with irradiation group (71.4%; Fisher’s exact test, p = 0.003). We observed a shorter duration of symptom, a higher rate of eventual exenteration and local recurrence, and a shorter time interval to local recurrence from initial management in poorly differentiated tumors compared with moderately differentiated tumors. Conclusion: It is critical to achieve a negative tumor margin in both frozen and permanent section to prevent local recurrence. Early aggressive management is required in sebaceous gland carcinoma of the lacrimal gland, as its mortality is much higher than that of eyelid origin.

Immunohistochemical Characterization of a Sebaceous Gland Carcinoma in a Gerbil (Meriones unguiculatus)

Sebaceous gland carcinoma is a common tumour in male gerbils but, to date, no information is available on its immunohistochemical properties. This report describes the histopathological and immunohistochemical features of such a tumour from a 4.5-year-old male gerbil. The tumour immunoreactivity profile was studied in respect of p53 protein, CEA, EMA, c-erbB-2, cytokeratin (CK) 14 and the CKs detected by AE1/AE3 antibodies (i.e. high molecular weight CKs 1, 2, 3, 4, 5, 6, 10, 14, 15 and 16, and low molecular weight CKs 7, 8 and 19). The differences observed in p53 and c-erbB-2 immunolabelling between carcinomatous and hyperplastic areas suggest that p53 mutations and amplification of c-erbB-2 may play a significant role in the oncogenesis of sebaceous gland carcinoma in the gerbil.

Differenzialdiagnose und Therapieoptionen bei Tumoren der Konjunktiva

The diagnostic classification of most conjunctival tumors is based on case history, inspection, and examination with the slit lamp microscope. Further imaging procedures are rarely indicated when malignant processes are not circumscribed. Clinical classification then also includes palpation and echographic examination of regional lymph nodes. Pigmented and nonpigmented melanocytic nevi are the most frequent conjunctival tumors. An important practical biomicroscopic cardinal symptom of the most frequent nevi is the presence of epithelial pseudocysts. Essential in practice is the histopathological confirmation of the clinical diagnosis, e.g., distinguishing between nonpigmented melanomas and sebaceous gland carcinomas with a pagetoid growth pattern or squamous cell carcinomas. Depending on the course and findings, the following therapeutic measures can be indicated: cryotherapy, chemotherapy, radiotherapy, modified enucleation, orbital exenteration, or a combination of different methods.

Therapierefraktäre Blepharokonjunktivitis bei einer 90-jährigen Patientin

Sebaceous gland carcinoma can clinically mimic benign conditions such as chalazion and blepharoconjunctivitis. This carcinoma should be histologically excluded for every unilateral, recalcitrant chalazion and every unilateral, therapy refractory blepharitis. Autosomal dominant Muir-Torre syndrome should be considered in patients who develop sebaceous gland carcinoma of the ocular adnexa. In this case, the sebaceous gland carcinoma is combined with visceral carcinoma.

Sentinel Lymph Node Biopsy for High-Risk Nonmelanoma Skin Cancers

Although the utility of the sentinel lymph node biopsy (SLNB) in the staging of melanoma is well established, its usefulness in high-risk nonmelanoma skin cancer (NMSC) is yet to be determined. The objective was to report our experience with patients who underwent SLNB for the staging of a high-risk NMSC. We identified 13 patients with a high-risk NMSC who underwent SLNB between 1998 and 2006 and conducted a retrospective review of their medical records and tumor pathology. Their status as regards tumor recurrence and survival was obtained when possible. Of 13 patients, 9 had squamous cell carcinoma (SCC), 2 had sebaceous gland carcinoma, 1 had porocarcinoma, and 1 had atypical fibroxanthoma. All SLNB were negative for metastatic disease, but 1 appeared to be a false-negative finding. Compared to melanoma, SCC of the skin are much less predictable as regards their tendency to metastasize to the regional lymph nodes. Although the SLNB appears to be a reliable staging procedure for NMSC (especially SCC), the yield may be too low to justify its routine use in this patient population. More data are needed to determine when a SLNB is justified in the management of NMSC.

The Switch Flap in Eyelid Reconstruction

Purpose: Full-thickness eyelid defects are conventionally reconstructed by either a Hughes flap or a Cutler-Beard bridge flap. The switch flap is an alternative method and is not very widely practiced. The author has used this method for repair of large full-thickness eyelid defects and describes her experience with the use of this technique. Method: Eight cases of large full-thickness eyelid defects resulting from excision of tumours such as basal cell carcinoma (bcc), squamous cell carcinoma (scc) and sebaceous gland carcinoma (sgc) were taken for repair using the switch flap technique. The technique involves switching a full-thickness flap on a pedicle to fill a defect from lower lid to upper or vice versa. The pedicle is divided in three weeks. The recipient lid is reconstructed by direct closure and the donor lid by direct closure with or without cantholysis or sliding flap, or it is left to heal by second intention. The patients were followed up frequently in the first few weeks according to need, at six months, and then every year for five years before discharge. At these visits, contour of lid, condition of wound, cornea and donor site were examined for infection, dehiscence, corneal ulcer, notching, trichiasis, and recurrence. The preoperative and postoperative photographs were also compared. Results: Out of the eight cases of eyelid defects, one was from squamous cell carcinoma, three were from sebaceous gland carcinoma, and four were from infiltrative basal cell carcinoma. Using the switch flap technique, the defects resulting from their excision were completely covered in all cases. The main complication was a corneal ulcer in cases 1 and 3 where the flap had crossed the central cornea. A bandage contact lens was inserted until the division of the flap. The main morbidity was the blurred vision until the flap is divided, especially in the cases of reduced vision in the other eye. At about 4–6 weeks post flap division, the recipient and donor sites have healed completely, even when the donor lid was left to heal by second intention (case 4). There was no trichiasis, notching or notable deformity, and the morbidity was minimal. A comparison between preoperative and postoperative photographs shows satisfactory results with the switch flap technique. Conclusion: The author has found the switch flap technique very useful for reconstruction of large full-thickness eyelid defects resulting from tumour excision as this method results in complete repair of defects with a full-thickness flap, tarsus, lid margin and eyelashes and without causing notable deformity at the donor site. The switch flap can successfully replace the Hughes flap technique and Cutler-Beard technique for repair of large eyelid defects.

Role of fine needle aspiration cytology in diagnosis of eyelid sebaceous carcinoma

Sebaceous carcinoma of the ocular adnexa is a malignant neoplasm which can exhibit aggressive local behavior and can metastasize to regional lymph nodes and distant organs. The neoplasm is known to masquerade as other benign and less malignant lesions, resulting in delay in diagnosis and relative high morbidity and mortality. Fine needle aspiration cytology (FNAC) of recurrent upper eyelid nodules treated elsewhere as chalazion was done. Cytological smears were suggestive of malignancy. Subsequently histopathology confirmed the diagnosis of sebaceous gland carcinoma. Eyelid reconstruction was done after histopathologically confirmed tumor-free margins. The article highlights the role of FNAC in early diagnosis and subsequent appropriate surgical management of eyelid sebaceous gland carcinoma to prevent recurrence and metastasis.

Selective Removal of Sebaceous Gland Carcinoma of the Lower Eyelid With Orbital Infiltration

A 74-year-old woman presented with a nodule on the right lower eyelid. An incisional biopsy was significant for sebaceous gland carcinoma, whereas magnetic resonance imaging revealed infiltration of the ipsilateral orbit, including the medial and lower rectus muscles. The lesion was selectively excised, including the infiltrated part of the lower lid and the intraorbital part of the tumor. Two years postoperatively, no recurrence or metastasis have been noted. Preoperative orbital imaging is mandatory in cases of sebaceous gland carcinoma because it can reveal clinically silent orbital invasion. In such cases, selective surgical excision may be used, avoiding orbital exenteration.

Orbital exenteration for invasive skin tumours

Orbital exenteration aims at local control of disease invading the orbit that is potentially fatal or relentlessly progressive. Of all exenterations presenting to ophthalmologists, 40-50% are required for tumours in the eyelid or periocular skin. 99% of these are basal cell carcinomas and 4-6% each are squamous cell carcinomas or sebaceous gland carcinomas. Orbital invasion results in progressive fixation of the tumour to bone and reduced ocular motility. Perineural invasion of branches of the trigeminal nerve leads to numbness or pain, and that the facial nerve, to weakness. Biopsy identifies the cell type and the presence of perineural invasion. CT and MRI scanning help in the assessment of tumour spread within the orbit. Management should be in collaboration with an oncologist. Exenteration may be total-the removal of all orbital contents-or lid-sparing if the tumour is placed posteriorly. The socket may be allowed to heal by granulation or lined with a split skin graft or local flap. Complications may be seen following 20-25% of exenterations and include fistulae, tissue necrosis, exposed bone, and infection. Incomplete clearance of tumours occurs in about 38% of total exenterations and 17% of subtotal. The overall 5-year survival is 55-65%, but significantly worse if there was perineural spread. Facial prostheses may be mounted on glasses or secured with tissue glue or osseointegrated implants. Excellent cosmetic results can be achieved but many patients prefer to wear a patch.

Exenteração: estudo retrospectivo

To review all cases of orbit exenteration performed at the Orbit Sector, Ophthalmology Department - Federal University of São Paulo, from 1998 to 2003. We reviewed conditions leading to orbital exenteration in 21 patients at the Orbit Sector of Unifesp-EPM from August 1998 to May 2003. Data regarding sex, age, race, primary lesion site, visual acuity at the moment of diagnosis, previous surgeries related to the exenteration, type of performed surgery, histopathologic diagnosis, postoperative complications and use of adjuvant treatment were collected. 21 patient charts were retrospectively analyzed. Ages ranged from 5 to 91 years (mean of 58.5 years). Of these, 12 were male and 9 were female, most of them Caucasian. All lesions that led to exenteration were malignant neoplasias; however, none were metastatic. Lesions originated from eyelids in twelve patients, from bulbar conjunctiva in six and from the orbit in three. Cases were also classified as squamous cell carcinoma (eleven cases), basal cell carcinoma (four cases), sebaceous gland carcinoma (two cases), rhabdomyosarcoma (two cases), mucoepidermoid carcinoma (one case) and adnexal microcistic carcinoma (one case). Visual acuity at the moment of diagnosis ranged from 20/40 to no light perception. Only six patients had been submitted to previous surgeries related to the exenteration. After surgery, three patients suffered graft necrosis, one presented ethmoidal sinus fistula to the orbit and one presented orbital socket shrinkage. Six patients needed postoperative radiotherapy and two had been previously submitted to chemotherapy. Most patients analyzed in our study presented lesions that are usually small in the beginning; however, they can disseminate to the orbit in the absence of adequate treatment.

Management of malignant and benign eyelid lesions

The management of benign and malignant eyelid neoplasms has been extensively examined. This paper offers an overview of the most common eyelid lesions and their management based on a review of the relevant bibliography. Recent studies have focused on the results of nonsurgical approaches for benign and premalignant lesions that are routinely surgically excised. In the malignant group, a consensus has been reached over the preferred method of tumor excision for basal cell carcinoma: Mohs surgery or complete surgical excision with frozen-section control of the margins offers the lowest tumor-recurrence rate. Important acquisitions have been made on squamous cells for which sentinel node biopsy may reveal early metastatic cancer. Intraepithelial tumor growth is a peculiar feature of sebaceous gland carcinoma that seems to indicate an increased risk for orbital invasion. Recent reports regarding the rare tumor, Merkel cell carcinoma, recommend a wide surgical excision with 5 mm margins; this may reduce the incidence of lymph-node metastasis, haematogenous spread and local recurrences. Although treatment of the most common benign and malignant tumours affecting the eyelids has not radically changed over the years, recent reports have significantly improved the standard of care for affected patients.

Sebaceous Gland Carcinoma as the Initial Clue to Occult Colon Carcinoma (Muir-Torre Syndrome)

Sebaceous Gland Carcinoma as the Initial Clue to Occult Colon Carcinoma (Muir-Torre Syndrome)

Immunohistochemical staining for adipophilin, perilipin and TIP47

Background: The presence of lipid in the cell cytoplasm is useful for supporting the diagnosis of sebaceous gland carcinoma (SGC). Currently this requires histochemical stains that are carried out on...

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients

Periocular sebaceous gland carcinomas (SGCs) occur in the eyelids either sporadically or as a phenotypic feature of Muir-Torre syndrome (MTS). In knockout mice mismatch-repair (MMR) defects or inactivation of the fragile histidine triad (FHIT) gene are associated with MTS-like signs, including SGC. To dissect the genetic alterations associated with microsatellite instability (MSI) and inactivation of the FHIT gene, we studied nine periocular SGC specimens from MTS patients. Immunohistochemistry was performed for FHIT, MSH2, MLH1, and MSH6. We assessed MSI as well as loss of heterozygosity (LOH) at the FHIT locus with polymorphic markers and genomic multiplex PCR. Epigenetic silencing was detected by methylation-specific PCR (MSP) and combined bisulfite restriction analysis (COBRA). Our analyses identified two SGCs with FHIT positivity and high-grade MSI, and seven cases with loss of FHIT and microsatellite stability (MSS). MSI correlated with loss of MSH2 and MLH1 immunostaining. Loss-of-function mechanisms affecting the FHIT gene were identified as intragenic deletions eliminating the coding exons 5 and 6 on one hand, and complete biallelic methylation of the FHIT transcription regulatory region on the other hand. Germinal FHIT mutations as a predisposing factor for MTS were excluded in two index patients with cancer in three generations, including an FHIT-negative SGC. Our data suggest that either somatic inactivation of the FHIT gene associated with MSS or inactivation of the MMR system resulting in MSI contribute to the development of periocular SGCs in presumptive MTS.