Synchronous Bilateral Ovarian Mesonephric-like Adenocarcinomas with Separate Origins from High-Grade Mullerian Adenosarcoma and Endometriosis: Report of a Rare Case.

Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.

Acne agminata: dermoscopic features and a short review.

Acne agminata is a rare idiopathic inflammatory dermatosis. Treatment is variable with no clear consensus. We herein report a case of a 31-year-old man with sudden onset papulonodular eruptions on his face over two months. Histopathological examination revealed superficial granuloma composed of epithelioid histiocytes and scattered multinucleated giant cells, confirming acne agminata. Dermoscopy showed focal orangish structureless areas with follicular openings with white keratotic plugs. He achieved complete clinical resolution with oral prednisolone in 6 weeks. We also reviewed the literature regarding the reported treatment regimens used.

Cutaneous Presentation of Angioimmunoblastic T-Cell Lymphoma: A Harbinger of Poor Prognosis?

A 62-year-old woman presented with a 2-year history of extensive, pruritic dermatosis over her face, trunk, and limbs. She was initially treated for psoriasis with methotrexate 5 mg twice weekly and topical clobetasol cream; however, her condition worsened, and she was admitted for generalized exfoliative dermatitis. Examination showed generalized erythema and scaling affecting her face (Figure 1A), chest (Figure 1B), back, and limbs. There were also cervical, axillary, and inguinal lymphadenopathy. Laboratory studies revealed a high white blood cell count of 125×109/L (reference range: 4-10×109/L), hemoglobin level of 11.9 g/dL (reference range: 12-16 g/dL), and normal platelet level of 396×109/L (reference range: 140-440×109/L). Results from direct Coombs test were negative and lactate dehydrogenase levels were normal.

Characteristics and behaviour of screen-detected ductal carcinoma in situ of the breast: comparison with symptomatic patients.

Breast cancer is the most common malignancy in Singapore women. Ductal carcinoma in situ (DCIS) is the putative, non-obligate precursor of the majority of invasive breast cancers. The efficacy of the Singapore breast-screening pilot project in detecting early stage breast cancer led to the launch of a national breast-screening programme, BreastScreen Singapore (BSS), in January 2002. In this study, we compared clinicopathological and immunohistochemical characteristics, as well as clinical outcomes, between screen-detected and symptomatic DCIS. The study cohort comprised 1202 cases of DCIS diagnosed at Singapore General Hospital from 1994 to 2010. Comparison of clinicopathological parameters, immunohistochemical results of ER, PR, HER2, CK14, EGFR, and 34ßE12, and clinical outcomes was carried out between the 2 groups. Amongst 1202 cases, 610 (50.7%) were screen-detected and 592 (49.3%) were symptomatic DCIS. Screen-detected cases were smaller in size (P < 0.001), of lower nuclear grade (P = 0.004), and more frequently expressed ER (P < 0.001). Luminal A phenotype was more frequently observed in screen-detected DCIS, while triple-negative and HER2 phenotypes were more common in symptomatic DCIS (P < 0.001). The basal-like phenotype was also more frequent in symptomatic DCIS (P = 0.041). Mean and median follow-up was 99.7 and 97.8 months, respectively, with a maximum follow-up of 246.0 months. More symptomatic patients developed invasive recurrences compared to screen-detected patients (P = 0.001). A trend for better disease-free survival was observed in screen-detected patients (P = 0.076). Patients who were screen-detected experienced better overall survival than those with symptomatic DCIS (P = 0.007). Our data indicate a more favourable outcome of screen-detected DCIS patients confirming the role of BSS in early identification of this curable disease.

Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape. METHODS: Immunohistochemical staining on the scrotal wall tumor and bone marrow metastasis demonstrated HER2 overexpression. Whole genome sequencing of the tumor and matched blood was performed. RESULTS: Notable copy number gains (log2FC > 0.9) on chromosomes 7 and 8 were detected (n = 81), with 92.6% of these unique genes specifically located on chromosome 8. Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1. Interestingly, ERBB2 gene did not exhibit high copy number gain (log2FC = 0.4) although 90% of tumor cells stained HER2-positive. Enrichment in pathways associated with transforming growth factor-beta (TGFß) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3) was detected. Amplicon structure analysis revealed that this was a simple-linear amplification event. CONCLUSION: Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen.

Uterine leiomyosarcoma in asian patients: validation of the revised Federation of gynecology and obstetrics staging system and identification of prognostic classifiers.

BACKGROUND: In 2008, the Federation of Gynecology and Obstetrics (FIGO) revised their 1988 staging system for uterine leiomyosarcomas. In this article, we compare performance of the 2008 and 1988 FIGO systems. METHODS: Individual case data were manually culled. Staging was retrospectively assessed according to revised and 1998 FIGO criteria. Overall survival distribution was assessed by the Kaplan-Meier method. Harrell's concordance index was used to assess the discriminative ability of a fitted Cox model to predict overall survival. RESULTS: A total of 110 cases of uterine leiomyosarcomas were reviewed and data from 88 patients were analyzed. In all, 71% of cases were classified as stage I, 7% as stage II, 3% as stage III, and 19% as stage IV under the revised FIGO staging system. Nine patients (10.2%) were downstaged and none were upstaged. The revised FIGO system did not show a significant improvement over the 1988 FIGO system in the ability to discriminate the risk of death of patients between stages, with concordance indexes of 0.70 and 0.71, respectively. Most patients were classified as stage I with age, tumor grade, tumor size, and lymphovascular invasion as prognostic factors. CONCLUSION: The 2008 revised FIGO staging system for uterine leiomyosarcomas does not perform better than the 1988 system for uterine endometrial carcinomas. A better staging system is needed for these cases.

Penile melanosis with annular fibrillar pattern.

Penile melanosis is an uncommon but benign condition. Its appearance, however, can cause significant distress to patients. We report a case of a patient presenting with hyperpigmented annular penile macules, with a fibrillar pattern seen on dermoscopy. Histopathological examination revealed basal keratinocyte hyperpigmentation with no melanocytic proliferation or atypia, confirming our diagnosis of penile melanosis. The patient was managed conservatively. We also reviewed the literature surrounding the clinical assessment and management of penile melanosis. Future reports on this topic with clinical-dermoscopic-pathological correlations will aid further understanding of this seldom reported condition.

Surprise Lymph Node Histology in a Patient with Ovarian Serous Carcinoma.

We report a case of a sixty-three-year-old Chinese female with a known past history of primary, biopsy-diagnosed, ovarian high-grade serous carcinoma. Following three cycles of chemotherapy, she underwent total hysterectomy, bilateral salpingo-oophorectomy cytoreductive surgery with lymphadenectomy, and multiple peritoneal biopsies. In this situation, the lymph nodes would be expected to demonstrate possible residual metastatic serous carcinoma with or without chemotherapy effect. The final diagnostic assessment in the lymph nodes, in this patient, however, was a rare combination of the following pathologies: metastatic serous carcinoma, with areas of chemotherapy effect, and incidental PEComatosis, focally in association with endometriosis, both within lymph nodes and surrounding connective tissue. PEComas have been described in patients with the tuberous sclerosis complex, but the current patient was not known to suffer from this condition. This case is also unusual, as although PEComas have been described as arising in the female genital tract, the associated phenomenon of endometriosis is exceedingly rare, and this is the first known reported case of lymph nodes harbouring a similar combination of pathologies.

MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases.

AIM: To determine the frequency of MED12 mutations in a series of 112 breast phyllodes tumours, and to correlate the findings with clinicopathological parameters and survival outcomes. METHODS: Phyllodes tumours from the Department of Pathology, Singapore General Hospital, were classified into benign, borderline and malignant categories. Genomic DNA from formalin-fixed paraffin-embedded phyllodes tumours was extracted, purified and subjected to ultra-deep-targeted amplicon sequencing across exon 2 of the MED12 gene. Sequencing was performed on the Illumina MiSeq next-generation sequencing platform and bioinformatics analysis applied. Appropriate statistical analyses were carried out. RESULTS: There were 66 benign, 32 borderline and 14 malignant tumours, with 43 (65.1%), 21 (65.6%) and 6 (42.8%) disclosing MED12 mutations (missense, splice site, indel), respectively. For 97 cases with available follow-up, there were 10 (10.3%) recurrences. Patients with phyllodes tumours that harboured MED12 mutations experienced improved disease-free survivals, with higher recurrence likelihood in those without MED12 mutations (HR 9.99, 95% CIs 1.55 to 64.42, p=0.015). CONCLUSIONS: Similar to fibroadenomas, phyllodes tumours show a high frequency of MED12 mutations, affirming the close biological relationship between these fibroepithelial neoplasms.

HER2 amplification and clinicopathological characteristics in a large Asian cohort of rare mucinous ovarian cancer.

Mucinous epithelial ovarian cancer has a poor prognosis in the advanced stages and responds poorly to conventional chemotherapy. We aim to elucidate the clinicopathological factors and incidence of HER2 expression of this cancer in a large Asian retrospective cohort from Singapore. Of a total of 133 cases, the median age at diagnosis was 48.3 years (range, 15.8-89.0 years), comparatively younger than western cohorts. Most were Chinese (71%), followed by Malays (16%), others (9.0%), and Indians (5%). 24% were noted to have a significant family history of malignancy of which breast and gastrointestinal cancers the most prominent. Majority of the patients (80%) had stage I disease at diagnosis. Information on HER2 status was available in 113 cases (85%). Of these, 31 cases (27.4%) were HER2+, higher than 18.8% reported in western population. HER2 positivity appeared to be lower among Chinese and higher among Malays patients (p = 0.052). With the current standard of care, there was no discernible impact of HER2 status on overall survival. (HR = 1.79; 95% CI, 0.66-4.85; p = 0.249). On the other hand, positive family history of cancer, presence of lymphovascular invasion, and ovarian surface involvements were significantly associated with inferior overall survival on univariate and continued to be statistically significant after adjustment for stage. While these clinical factors identify high risk patients, it is promising that the finding of a high incidence of HER2 in our Asian population may allow development of a HER2 targeted therapy to improve the management of mucinous ovarian cancers.

Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins.

AIM: To define a predictive model for clinical behaviour of breast phyllodes tumours (PT) using histological parameters and surgical margin status. METHODS: Cases of breast PT diagnosed in the Department of Pathology Singapore General Hospital between January 1992 and December 2010 were stratified into benign, borderline and malignant grades based on a combination of histological parameters (stromal atypia, hypercellularity, mitoses, overgrowth and nature of tumour borders). Surgical margin status was assessed. Clinical follow-up and biostatistical modelling were accomplished. RESULTS: Of 605 PT, 440 (72.7%) were benign, 111 (18.4%) borderline and 54 (8.9%) malignant. Recurrences, which were predominantly local, were documented in 80 (13.2%) women. Deaths from PT occurred in 12 (2%) women. Multivariate analysis revealed stromal atypia, overgrowth and surgical margins to be independently predictive of clinical behaviour, with mitoses achieving near significance. Stromal hypercellularity and tumour borders were not independently useful. A nomogram developed based on atypia, mitoses, overgrowth and surgical margins (AMOS criteria) could predict recurrence-free survival at 1, 3, 5 and 10 years. This nomogram was superior to a total histological score derived from adding values assigned to each of five histological parameters. CONCLUSION: A predictive nomogram based on three histological criteria and surgical margin status can be used to calculate recurrence-free survival of an individual woman diagnosed with PT. This can be applied for patient counselling and clinical management.