Prevalence of the EGFR T790M and other resistance mutations in the Australian population and histopathological correlation in a small subset of cases.

We sought to review the prevalence of EGFR T790M and other EGFR mutations associated with either proven or probable tyrosine kinase inhibitor (TKI) resistance in the Australasian lung cancer population and to perform histopathological correlation in a subset of cases. Retrospective statistical analysis was performed on a set of targeted lung cancer gene mutation tests (FIND IT gene panel) performed at Sonic Healthcare during 2018 and early 2019. A total of 1833 lung adenocarcinoma tumour samples underwent somatic mutation testing. EGFR mutations were found in 28% (n=514) of patients, in whom 9.3% (n=48) T790M mutations were present (always combined with other EGFR mutations) and 4.8% (n=25) exon 20 insertions were found. We also compared the prevalence of EGFR mutations identified in our population with that of the four largest publicly available lung cancer cohorts (total n=576 samples). Finally, a subset of 38 samples of primary/and or metastatic lung adenocarcinomas from 23 patients, including five with serial biopsies, underwent detailed morphological analysis. No reproducible morphological correlates were found to be associated with T790M, exon 20 resistance mutations or rarer co-occurring EGFR mutations. Although this may be subject to referral bias towards patients with resistant disease, the incidence of EGFR and T790M mutations is higher in this series from an Australasian population than in other similar publicly available lung adenocarcinoma cohorts. We conclude that histopathological features cannot be used to predict the acquisition of EGFR resistance.

Increasing tumor thickness is associated with recurrence and poorer survival in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine tumor usually occurring on sun-exposed skin in elderly patients. Clinical and pathologic factors associated with disease progression and mortality in patients with MCC are poorly defined. Recently, it has been reported that p63 expression in primary MCC is strongly associated with clinical outcome. METHODS: MCC patients diagnosed between July 1, 1993 and July 31, 2009 were identified from the surgical pathology records of the Sydney South West Area Health Service. Clinical, pathologic, treatment, and survival data were obtained and immunohistochemical analyses for p53, p63, and Ki-67 were performed. The associations of clinical and pathologic features with disease-free and disease-specific survival were analyzed. RESULTS: Ninety-five patients were identified (67 males, 28 females; median age at diagnosis of primary MCC 76 [range, 42-93] years). Increasing primary tumor thickness was significantly associated with poorer disease-free survival (5-year survival 18 % in tumors >10 mm thick compared with 69 % for patients with tumors ≤10 mm thick, p = 0.002) and disease-specific survival (5-year survival 74 % in tumors >10 mm thick compared with 97 % for patients with tumors ≤10 mm thick, p = 0.006). There was a strong positive correlation between the Ki-67 index (proportion of Ki-67-positive tumor nuclei) and tumor thickness (r = 0.39, n = 45, p = 0.008). Positive staining for p63 in MCC was infrequent (9 % of primary MCC) and showed no significant association with disease outcome. CONCLUSIONS: Tumor thickness is significantly associated with disease-free survival in MCC. We recommend that primary tumor thickness be routinely recorded in the pathology reports of patients with primary MCC.

Two cases of adenosquamous carcinoma of the cervix with extensive in situ and invasive endometrial extension.

Adenosquamous carcinoma of the cervix is rare. It is defined as having both glandular and squamous cell differentiation, each component malignant and clearly seen on haematoxylin and eosin-stained slides alone. We report two cases of adenosquamous carcinoma of the uterine cervix, both of which showed in situ and invasive components and both of which showed cephalad extension to involve the endometrium with invasive squamous and adenocarcinomatous components. The mechanisms for cephalad endomyometrial extension is discussed, as are the potential implications for management and staging.

Retroperitoneal inflammatory liposarcoma in a patient with non-hodgkin lymphoma: a report highlighting diagnostic pitfalls.

Well differentiated liposarcoma (WDLS) is the commonest subtype of liposarcoma. Recognised subtypes of WDLSs are lipoma-like, sclerosing, spindle cell and inflammatory. The inflammatory variant of WDLS also known as "lymphocyte-rich liposarcoma" is rare. We present a case of inflammatory WDLS occurring in the retroperitoneum, in a patient with a past history of non-Hodgkin lymphoma. We outline the histological features, discuss the differential diagnoses and highlight the diagnostic pitfalls in interpretation of this lesion on fine needle biopsy.

Papillary cystadenoma of a minor salivary gland: report of a case involving cytological analysis and review of the literature.

A 91-year-old man presented with an asymptomatic swelling in the roof of his mouth. Clinically the lesion was nontender and appeared cystic. A CT scan showed a soft tissue swelling of his palate with no bony involvement. An orthopantogram and blood tests were noncontributory. A fine-needle aspiration biopsy was suggestive of a minor salivary gland neoplasm. An excision biopsy showed papillary cystadenoma of the minor salivary gland, with numbers of psammoma bodies. A stepwise approach is demonstrated in the diagnosis of this rare minor salivary gland neoplasm. To the authors' best knowledge, this is the 12th case of this tumor seen in the palate. Furthermore, no previous case has included a fine-needle aspiration biopsy in the work-up, the cytological features of which will be described.

Hypothermia fatalities in a temperate climate: Sydney, Australia.

AIMS: Fatal hypothermia is well known to occur in cold climates, with previous case series reflecting this. However, hypothermia can also occur in temperate climates. This case series describes the features and circumstances surrounding hypothermia-related deaths in Sydney, Australia. METHODS: The files of hypothermia-related deaths were reviewed at the Department of Forensic Medicine, Glebe between 1 January 2001 and 31 December 2005 via a search of electronic autopsy records. RESULTS: Twenty-four cases of fatal hypothermia were found. Many of the deaths occurred in winter (46%). The mean age was 76 years (range 56-92), with a female predominance (63%). Risk factors for hypothermia were identified in 58%. The mean body mass index (BMI) was 22 (range 15-33). Nineteen cases (79%) were found indoors. Four decedents were found naked, four were dressed in minimal amounts of clothing, and paradoxical undressing was found in seven cases. Pathological findings included gastric erosions (79%), and patchy reddish brown discoloration over large joints (75%). The majority of cases had significant pre-existing natural disease processes. Out of 18 cases where toxicology was performed, alcohol was detected in four cases, while other psychotropic agents were present in four deaths. No illicit drugs were detected. CONCLUSION: This study shows that fatal hypothermia, a significant public health problem, is not limited to cold climates. Forensic pathologists in Australia need to be aware of this condition, and not dismiss death as due to natural disease processes.

Recurrent spontaneous coronary artery dissection: A case report and review of the literature.

Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome. Recurrent spontaneous dissection is even more rare. A case of recurrent coronary artery dissection is reported and the literature is reviewed.

Squamous cell carcinoma arising in an area of long-standing necrobiosis lipoidica.

BACKGROUND: Squamous cell carcinoma in an area of chronic ulceration is a well-documented phenomenon. However, its occurrence arising de novo in an area of necrobiosis lipoidica is rare. METHOD: We report a case in a 53-year-old female who presented with a 2 month history of an erythematous nodule occurring in a plaque of necrobiosis lipoidica on the medical aspect of the right lower leg. She had a background of poorly controlled Type 1 diabetes. RESULTS: Histopathological findings revealed a well-differentiated squamous cell carcinoma overlying an area of necrobiosis lipoidica. Treatment was by excision and split-thickness skin graft. CONCLUSION: Clinicians should be aware of malignant transformation within a plaque of necrobiosis lipoidica. Early detection will allow conservative treatment.

Seborrhoeic keratoses with associated lesions: a retrospective analysis of 85 lesions.

Seborrhoeic keratoses are benign epidermal neoplasms that are rarely associated with other skin lesions especially malignancies. In this study, the aim was to assess the incidence of associated lesions occurring either adjacent to or contiguous with a seborrhoeic keratosis. A retrospective case series over a 12-month period was carried out. In total, 639 consecutive histologically diagnosed seborrhoeic keratoses were identified, of which 85 (9%) were found to be associated with other lesions. Of these associated lesions, 44 (7%) were malignant, with four of these found to be arising within the seborrhoeic keratosis. These associated lesions included premalignant lesions, malignancies, melanocytic lesions and miscellaneous lesions. Men (59%) were affected more commonly than women. The average age was 74 years (range 33-98 years). Seborrhoeic keratoses associated with other lesions were found most commonly on the head and neck. The incidence of associated lesions, in particular malignancy arising within seborrhoeic keratoses may be higher than previously thought. This may be an incidental phenomenon, or seborrhoeic keratosis could represent a precursor lesion. Therefore, seborrhoeic keratoses that have undergone recent clinical change should be considered for biopsy and histological examination.

Colloid milium arising on a non-sun-exposed area in an adult.

A 59-year-old woman presented with multiple translucent papules on the inner surface of the tragus of the right ear. Initially they were treated with cryotherapy, with a later biopsy revealing the diagnosis of colloid milium. The histology was unusual for adult colloid milium as the lesion lacked a Grenz zone and evidence of solar elastosis. This together with a lack of aetiological factors made it difficult to classify the subtype of colloid milium.

Quality of life in psoriasis improves after standardized administration of narrowband UVB phototherapy.

SUMMARY Psoriasis is a chronic fluctuating dermatosis with demonstrable impact on patients' quality of life. Our aim was to investigate if narrowband UVB phototherapy administered to psoriatic patients in a standardized manner leads to an improvement in patients' perceived quality of life. A total of 138 patients with psoriasis were recruited from referrals to the Skin and Cancer Foundation, Australia between January 1998 and September 2002. Patients had psoriasis inadequately controlled by topical therapies alone and no contraindications to the use of phototherapy. Patients completed a pre- and post-therapy questionnaire on quality of life parameters. The differences in mean and standard deviation of quality of life parameters were measured using a paired sample t-test based on pre- and post-phototherapy questionnaires. Ninety patients were included in the study. Forty-eight patients were excluded as they had not completed post-phototherapy questionnaires. The course of narrowband UVB phototherapy was found to significantly improve quality of life in psoriasis patients (P

Renal cell carcinoma with cutaneous metastases.

An 86-year-old man presented with multiple papules on his face, neck, lips and ears 4 years after a left nephrectomy for renal cell carcinoma. Shave biopsies and excisions of the cutaneous lesions revealed findings consistent with metastatic renal cell carcinoma of clear cell type. The patient continued to present to the clinic over the next 3 years with similar eruptions, and biopsies continued to confirm renal cell carcinoma. During this time, metastases to the bone, lung, soft palate and posterior leg were also diagnosed. This case represents an unusual clinical presentation of metastatic renal cell carcinoma. It shows that a high index of suspicion should be maintained as cutaneous metastases can mimic other skin conditions.