Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1.

Clear cell odontogenic carcinoma (CCOC) is a rare, low-grade malignant epithelial neoplasm, occurring in the jawbones, mainly affecting the mandible of elderly patients. In addition to hyalinizing clear cell carcinoma of the salivary gland, it is one of the epithelial neoplasms known to harbor an EWSR1-ATF1 fusion. Therefore, a link between these tumors seems plausible. We describe six cases of CCOC showing EWSR1 rearrangements, with two cases being positive for the ATF1 partner gene using FISH analysis. In one case, an EWSR1-CREB1 fusion was identified using RT-PCR, which we report for the first time in this tumor type. The other three cases investigated by FISH were negative for ATF1, CREB1 and CREB3L2. In conclusion, our data show that EWSR1-CREB1 is an alternative fusion gene to EWSR1-ATF1 in CCOC.

Emphysematous cholecystitis due to Clostridium perfringens successfully treated by cholecystectomy.

Emphysematous Cholecystitis is life threatening if left untreated. It is associated with arteriosclerosis, embolic events, and diabetes mellitus. In this report, a patient was presented with an early diagnosis of Emphysematous Cholecystitis and was treated by cholecystectomy without complications. A 46-year-old male presented at the emergency department. Laboratory results as well as the abdominal ultrasound showed no abnormalities. One day after admission, infection parameters started rising. A computed tomography (CT) showed cholecystitis with a circular gas pattern in bile ducts and gallbladder. After treatment with cholecystectomy and antibiotics, the patient recovered uneventfully. The gallbladder mucosa was denaturized with signs of necrosis. The bile culture was positive for Clostridium perfringens. Treatment was based on preoperative antibiotic treatment combined with cholecystectomy. This resulted in early clinical improvement of the patient and normalization of infection parameters. Therefore, the patient was discharged from the hospital four days postoperatively.

Photodynamic therapy in Bowen's disease: influence of histological features and clinical characteristics on its success.

BACKGROUND: In Bowen's disease (BD) there is no consensus on optimal treatment. Photodynamic therapy (PDT) is an effective non-invasive treatment modality for BD with excellent cosmetic results. OBJECTIVE: This retrospective study examines whether clinical and histological features of BD impact PDT response. METHODS: Patients with previously untreated BD from 2002 until 2007 were identified at the Maastricht University Medical Centre. Patients treated with PDT were included. All histological slides were re-examined. RESULTS: During the study period 98 tumours were treated with PDT. In univariate analysis severe atypia and higher age were associated with decreased probability of clinical clearance. Higher age was also associated with an increased risk of recurrence. In multivariate analysis severe atypia remained the only independent risk factor for therapy failure. CONCLUSION: In patients with BD, severe atypia and higher age are associated with an increased risk of treatment failure after PDT.

Correlation between histological findings on punch biopsy specimens and subsequent excision specimens in cutaneous squamous cell carcinoma.

Diagnosis and subsequent treatment of cutaneous squamous cell carcinoma are frequently based on punch biopsies. Regarding the current TNM classification and stage grouping for cutaneous squamous cell carcinoma, it is important to identify the high-risk features (infiltration depth > 4 mm, perineural and/or lymphovascular invasion and poor differentiation). This study investigates the agreement of histological high-risk features and TNM grouping stage on 3 mm punch biopsies and subsequent surgical excision in 105 patients diagnosed with cutaneous squamous cell carcinoma. On punch biopsy, infiltration depth > 4 mm is not identified in 83.3% (30/36), perineural invasion in 90.9% (10/11) and poor differentiation in 85.7% (6/7) of cases. The TNM stage was underestimated on punch biopsy in 15.4% (16/104). This study shows that on a 3 mm punch biopsy, high-risk features in cSCC can remain undetected and that the actual TNM stage is not identified in 1 out of 6 tumours.

Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. OBJECTIVES: To determine whether HIF1/mTOR signalling is involved in BCC and TE. METHODS: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, <30%, 30-80% and >80%). RESULTS: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1α), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. CONCLUSIONS: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

Bowen's disease: A six-year retrospective study of treatment with emphasis on resection margins.

Bowen's disease is an in situ squamous cell carcinoma of the skin with various treatment modalities available. A major advantage of surgical excision is the opportunity to histologically examine the resection margins. There is no consensus about the most appropriate margin. This retrospective study evaluates the clearance rates achieved by excision with a 5 mm margin and estimates how that might change after fictitiously reducing the resection margin by 1 or 2 mm. Patients with histologically confirmed Bowen's disease were selected at the Maastricht University Medical Centre from 2002 until 2007. Surgical margins and complete excision rates were evaluated and histological slides were re-examined. To our knowledge this is the first study investigating the safety margin for Bowen's disease. As Bowen's disease is not an invasive disease, minimisation of healthy tissue excision is desirable. Our data show that a hypothetical reduction of the safety margin from 5 mm to 4 or 3 mm decreases the complete excision rate from 94.4% to 87% and 74.1%, respectively.

Clinical and histological prognostic factors for local recurrence and metastasis of cutaneous squamous cell carcinoma: analysis of a defined population.

Cutaneous squamous cell carcinomas (cSCC) can recur locally and can metastasize. The objective of this study was to identify clinical and histopathological prognostic factors for local recurrence and metastasis in cSCCs at any body site. Clinical and histopathological data were collected from 224 patients with cSCC. During the median follow-up period of 43 months (range 0-73 months) the cumulative probabilities of recurrence-free survival at 1, 2 and 4 years post-treatment were 98.0%, 96.9% and 94.7%, respectively, and for metastasis-free survival 98.1%, 97.0% and 95.9%, respectively. In univariate survival analyses, predictors for local recurrence were every millimetre increase in tumour diameter and in tumour thickness. Predictors for metastasis this was location on the ear, invasion of deeper structures, no surgical treatment, poor differentiation, every millimetre increase in tumour diameter and in tumour thickness. In multivariate survival analysis, every millimetre increase in both tumour diameter and tumour thickness were independent predictors for local recurrence as well as for metastasis and, therefore, it is important to report these in patients' files. Defining prognostic valuables is important for diagnostic work-up, treatment and follow-up for an individual patient.

Differentiation between basal cell carcinoma and trichoepithelioma by immunohistochemical staining of the androgen receptor: an overview.

Clinical and histopathological differentiation between basal cell carcinoma (BCC) and trichoepithelioma (TE) is a frequent problem. Attempts have been made to identify immunohistochemical markers helpful in differentiating them. A correct diagnosis is important because the tumours are treated differently. Recent studies showed the absence of androgen receptor (AR) expression in benign hair follicle tumours like TE. This study examines whether AR immunostaining is a useful diagnostic test to differentiate between BCC and TE. We randomly selected 75 cases with histological diagnoses of either BCC (subtypes: superficial, nodular or infiltrative) or TE (subtypes: classic or desmoplastic) from the database of the pathology department of Maastricht University Medical Centre. The available haematoxylin & eosin (H&E) slides were reviewed by three independent investigators using predetermined characteristics. Fifty-six slides (38 BCC and 18 TE) with unequivocal histological characteristics of either tumour were used for immunohistochemistry with AR antibodies. Any nuclear expression within the tumour was considered positive. AR expression was present in 5/8 classic TE, 0/10 desmoplastic TE, 22/23 superficial or nodular BCC and in 10/15 infiltrative BCC. Immunohistochemical stain for AR is useful to differentiate between TE and BCC; particularly in desmoplastic TE versus infiltrative BCC (specificity and positive predictive value of 100%).

Correlation between histologic findings on punch biopsy specimens and subsequent excision specimens in recurrent basal cell carcinoma.

BACKGROUND: The type of treatment for a basal cell carcinoma (BCC) depends on the histologic subtype. Histologic examination is usually performed on incisional biopsy specimens. In primary BCC, the histologic subtype is correctly identified with a punch biopsy in 80.7% of cases. In recurrent BCC, correct identification is more difficult because of discontinuous growth caused by scar formation. Because an aggressive histologic subtype has a significantly higher risk for recurrence in these tumors, the histologic subtype is at least as important in recurrent BCC as it is in primary BCC. OBJECTIVE: To investigate the correlation between histologic findings on punch biopsy specimens and subsequent excision specimens in recurrent BCC. Furthermore, we sought to clarify how often an aggressive histologic subtype was missed, based on the punch biopsy specimen. METHODS: We compared the histologic subtype in a punch biopsy specimen with the subsequent excision specimen in recurrent BCC. All BCCs were coded and judged randomly by the same dermatopathologist. RESULTS: In 24 of 73 investigated BCCs (32.9%), the histologic subtype of the initial biopsy did not match with the histologic subtype of the subsequent excision. Of the 37 excised BCCs with an aggressive histologic subtype, 7 (19%) were missed by the initial punch biopsy. LIMITATIONS: Intraobserver variation may have affected the results of this study. CONCLUSIONS: Discriminating tumors with any aggressive growth is relevant for treatment. However, in recurrent BCC, the histology of the biopsy specimen does not always correlate with the histology of the definitive excision. This may have important therapeutic implications.