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In patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important - those with classic histology and favorable T and M stage.Twenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of21 years; and American Joint Committee on Cancer (AJCC ) stage (8The median positive node number was 10 (range, 5-31). The median adjuvant I-131 dose was 158 mCi (range, 150-219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%.Recurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.

Hyalinizing trabecular tumor (HTT), a rare low-malignant-potential thyroid neoplasm, is usually treated with conservative surgery. However, cytomorphological diagnosis of HTT is challenging due to the significant overlap of nuclear features with more common malignancies such as papillary thyroid carcinoma (PTC), which usually requires more radical surgical intervention. To avoid unnecessary overtreatment, a precise diagnosis of HTT is therefore essential. Advances in molecular diagnostics provide the opportunity to overcome the limitations of cytological analysis. We present a case of HTT in a 71-year-old male who was initially suspected to be PTC based on cytopathology. However, further molecular analysis revealed PAX8::GLIS3 gene fusion, classifying the lesion as HTT and preventing surgical overtreatment. We discuss the diagnostic pitfall of cytopathology in HTT and suggest using emerging molecular genetic tools to avoid it.

Sclerosing polycystic adenoma (SPA) is an uncommon entity with fewer than 100 reported cases in the literature. Predominately affecting the major salivary glands, SPA typically presents as a painless, slow-growing mass in a middle-aged woman. The lesion’s histopathologic features are reminiscent of fibrocystic changes of the breast, but recent genetic studies provide evidence for a neoplastic process. We present a case of a sclerosing polycystic adenoma in a 69-year-old female with no significant medical history who was found to have a left parotid mass. This led to a fine needle aspiration (FNA) which was non-diagnostic. Superficial parotidectomy yielded a well-circumscribed unencapsulated mass with histologic and immunohistochemical features consistent with the diagnosis of SPA. We present this case to further characterize SPA, adding to the body of literature regarding the tumor’s presentation and histopathologic and immunohistochemical features.

Increasingly radical surgery combined with neo-adjuvant radiotherapy present a challenge for the reconstructive surgeon. The study objective was to review outcomes of Vertical Rectus Abdominis Myocutaneous (VRAM) flap-based perineal reconstruction following resectional surgery for pelvic malignancies. Single-centre retrospective analysis of patients undergoing immediate VRAM flap reconstruction of a perineal/pelvic defect for pelvic malignancy between July 2009 and November 2017. Primary outcome was perineal morbidity (surgical site infection (SSI), flap loss or dehiscence and perineal hernia). Secondary outcomes were length of stay and donor site morbidity (SSI, full-thickness dehiscence and incisional hernia). A total of 178 patients (96 females) were included. Median age was 67 years (range 28–88). The majority were performed for locally advanced rectal adenocarcinoma (n = 122; 68.5%) and 136 (76.4%) patients had received neoadjuvant radiotherapy. Four patients had complete flap loss (2.3%), and 40 had perineal dehiscence (22.5%); however, only, 18 patients required a return to theatre during the admission for perineal-related complications (10.1%). Abdominal dehiscence occurred in six patients (3.4%). Median length of post-operative stay was 15 days (6–131). Sixty-day mortality rate was 1.1%. SSI at the midline and perineum occurred in 34 (19.1%) and 38 patients (21.3%), respectively. At 90-day post-operatively, 75.6% of perineal wounds were healed. During a median follow-up of 44.5 months, twelve, eleven and 39 patients were diagnosed with perineal, midline and parastomal hernias, respectively (6.9%, 6.2% and 21.9%). It is important to have accurate knowledge of perineal and donor-site morbidity rates to allow an informed consent process.

Summary Background The vertical rectus abdominis myocutaneous (VRAM) flap is an established technique employed to reconstruct pelvic and perineal defects not amenable to primary closure. The aim of this study was to systematically review the morbidity of VRAM flap reconstruction following exenterative pelvic surgery. Materials and methods A systematic literature search was conducted by using Medline, EMBASE, and Cochrane databases. Abstracts of all studies published from inception to November 2019 were identified. Search terms used included ‘vertical rectus abdominis myocutaneous’, ‘vertical rectus abdominis musculocutaneous’ and ‘VRAM’. Only studies that described outcomes when a VRAM flap was used during exenterative pelvic surgery were included; case reports were excluded. The primary outcome measure was VRAM flap morbidity. Secondary outcome measures included donor site morbidity and hospital length of stay. Results Sixty-five studies with a total of 1827 patients were identified and included. Perineal reconstruction was most commonly performed following abdominal perineal excision of the rectum (APER) (n = 636 and 34.8%). Median patient age at surgery ranged from 38 to 78 years. Mean perineal flap morbidity was 27%, with a complete flap loss rate of 1.8% and a perineal hernia rate of 0.2%. Mean donor site morbidity was 15%, with an abdominal dehiscence rate of 5.5% and an incisional hernia rate of 3.3%. Conclusions While overall morbidity after VRAM flap reconstruction in pelvic visceral surgery is high; the risk of major complications remains low. These data are important when counselling patients for surgery.

Introduction In March 2020, South Wales experienced the most significant COVID-19 outbreak in the UK outside of London. We share our experience of the rapid redesign and subsequent change in activity in one of the busiest supra-regional burns and plastic surgery services in the UK. Methods A time matched retrospective service evaluation was completed for a seven week “COVID-19” study period and the equivalent weeks in 2018 and 2019. The primary aim was to evaluate plastic surgery theatre use, and evaluate the impact of service redesign. Comparison between study periods was tested for statistical significance using two-tailed t-tests. Results Operation numbers reduced by 64% and total operating time by 70%. General anaesthetic cases reduced from 41% to 7% (p

p16INK4a is a tumor suppressor protein that retards cell cycle progression from G1 to S phase. Prior studies have evaluated p16INK4a expression in odontogenic keratocyst and ameloblastoma, but data regarding other odontogenic cysts and tumors have been sparse.With IRB approval, cases from the following entities were identified from archives of the UF Oral Pathology Biopsy Service (2005-2015): benign incidental odontogenic rest, dentigerous cyst, lateral periodontal cyst, calcifying odontogenic cyst, glandular odontogenic cyst, odontogenic keratocyst, orthokeratinized odontogenic cyst, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and ameloblastoma. All cases were submitted for p16INK4a immunohistochemical testing.Results were scored as follows: nuclear and cytoplasmic staining of5% cells (score 0), 5%-25% (score 1), 25%-50% (score 2),50% (score 3). No significant difference in p16INK4a staining was noted between odontogenic cysts and the listed odontogenic tumors (chi-square, P = .540). When comparing lesions with higher recurrence rates (over 25% as reported in the literature) versus lesions with low recurrence rates (under 25%), higher recurrence correlated to significantly higher p16INK4a positivity (chi-square, P = .001). Follow-up testing was performed on 18 cases with "2" or "3" p16INK4a expression scores for high-risk HPV strains through HPV in situ hybridization (ISH) messenger RNA testing with no cases exhibiting a positive result.This study exhibits an association between increased p16INK4a positivity and odontogenic lesions with higher recurrence rates and highlights the role of p16INK4a as a progression marker unrelated to HPV expression in this group of pathologic entities.

Introduction When assessing paediatric patients presenting with burns, non-accidental injury always has to be considered. In our department, local policy dictates that all patients aged 18 or below should have a child safeguarding tool completed on initial clerking. Method A retrospective audit of all paediatric burns seen over one month was performed. Primary outcome measures included completion of a safeguarding tool and documentation of referral outcome. These results were presented locally and implementing changes were carried out. This was then re-audited over a further monthly period. Results Initial data collection showed a safeguarding tool completion rate of 69% and referral outcome documentation rate of 50% (n = 16). Implement changes included dissemination of initial audit results to the department, changing the layout of our clerking proformas and introducing posters in the unit which provided more information on risk assessing paediatric patients. The re-audit results showed a safeguarding tool completion rate of 100% and a referral outcome documentation rate of 100% (n = 14). Conclusions There was a significant improvement in both the safeguarding tool completion and referral outcome documentation rates following our interventions. Simple measures just such education and strategic adjustments of clerking proformas have been shown to be effective measures for increasing documental compliance of child safeguarding tools.

Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). This study describes a series of SC in minor glands with a literature review. We performed a retrospective search for oral SC, within the archives of the University of Florida, Oral Pathology and Surgical Pathology Biopsy services from 2010 to 2018. A total of 10 SCs were identified in the oral and maxillofacial region, four of which were in the minor salivary glands. The demographic, clinical, histological, and molecular findings were aggregated for all 4 cases. Patient age varied from 30 to 60 years, with an average of 45 years. Two cases each were in female and male patients. Two cases presented on the labial mucosa, and one each on the hard and soft palate. Immunohistochemical (IHC) staining showed mammaglobin positivity in all cases, GATA3 positivity in two cases, S100 positivity in three cases, and SOX10 positivity in only one case. Fluorescence in situ hybridization demonstrated positivity for ETV6-NTRK3 fusion in 4 cases. Although oral SC is rare, pathologists should be aware of the histologic overlap between the SC and other salivary gland neoplasms such as ACC and MEC. A judicious application of IHC staining would aid in diagnosis. SC should be considered in the differential diagnosis for intraoral salivary gland tumors.

The treatment of locally advanced vulvar carcinoma (LAVC) represents a major challenge. We investigated the role of pelvic exenteration as a treatment of LAVC. Women who underwent pelvic exenteration for primary and recurrent LAVC in our centre between 2001 and 2019 were included. Among the 19 women included during the study period, 14 women (73.7%) had primary LAVC while 5 women (26.3%) had recurrent disease. Surgical resection margins were microscopically clear (R0) in 94.7% of patients—14/14 undergoing primary treatment and 4/5 undergoing treatment for recurrent disease. Complete closure of the wound was achieved in 100% of women, with no wound left to heal by secondary intention. Tumour size was a predictor of requiring myocutaneous flap reconstruction, with all tumours less than 40 mm undergoing primary closure, while almost all tumours 40 mm diameter or greater (14/15 women) required flap reconstruction (p = 0.001). The 30-day major morbidity rate was 42% and there was no perioperative death. The mean overall survival was 144.8 months (2–206 months), with 1-, 2- and 5-year survival rates of 89.5%, 75.1% and 66.7%, respectively. In our centre, a primary surgical approach to the management of LAVC has resulted in good survival outcomes with acceptable morbidity rates.

BACKGROUND Pembrolizumab was recently approved as a first line agent for metastatic NSCLC in patients with high programmed death-ligand 1 (PD-L1) expression. OBJECTIVES Since a significant portion of lung cancer is diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA); there is a need for PD-L1 testing in these specimens. However, to date few studies have evaluated performance of cytology specimens from EBUS TBNA for PD-L1 analysis. METHODS Patients who had a diagnosis of NSCLC and in whom ancillary testing, i.e., next generation sequencing (NGS), anaplastic lymphoma kinase (ALK), and PD-L1 expression was requested between January and May 2017 were reviewed. RESULTS Fifty of the 112 patients reviewed had the diagnosis of NSCLC for which ancillary testing was requested. Twelve patients (24%) had squamous cell carcinoma, twenty-seven had adenocarcinoma (54%), five had NSCLC favor adenocarcinoma (10%), two had NSCLC favor squamous cell cancer (4%), and four had NSCLC not otherwise specified (NOS) (8%). Size of the lymph nodes or lesion sampled ranged from 10 to 50 mm. Four (8%) patients had insufficient number of tumor cells in the cell block for any of the ancillary molecular testing. Forty-one (82%) patients had an adequate sample for all three ancillary tests. Satisfactory results for PD-L1 expression for all cases was 86% with 14 (32%) patients having levels of PD-L1 expression >50%. CONCLUSION EBUS TBNA is effective and has a high proportion of satisfactory results for testing PD-L1 expression on tumor cells in addition to NGS and ALK FISH.

Primary tumors of the heart are uncommon; even rarer are primary cardiac neuroendocrine tumors. To our knowledge, only two cases have been described to date, both being high-grade tumors. We report a solitary low-grade neuroendocrine tumor of the heart, unexpectedly discovered during aortic valve repair for infectious bacterial endocarditis on the wall of the right ventricle in a 44-year-old man with a history of balloon valvulotomy as a child. Frozen section was sent intraoperatively and demonstrated a plasmacytoid neoplasm. Final pathology of the biopsies showed a tumor composed of both cohesive and discohesive plasmacytoid cells separated by a vascular network and strands of fibrosis. The tumor showed strong reactivity for AE1/3, synaptophysin, and CDX2 with focal reactivity for chromogranin-A and CD56. Neither necrosis nor a mitotic rate of greater than 2 mitoses per 2 mm2 was seen. A colonoscopy was performed and demonstrated only a tubular adenoma. An esophagogastroduodenoscopy was unremarkable. PET-CT DOTATATE, performed after complete resection of the tumor, demonstrated no abnormal radiotracer uptake. The patient continues to do well at present, 1 year later, and reports no symptoms attributable to carcinoid syndrome or disease progression. The patient was assigned by medical oncology to yearly follow-up and imaging, and is considered to have no evidence of disease.

Calciphylaxis is a rare systemic condition usually seen in patients with end-stage renal disease. It is characterised by pathological calcification of dermal blood vessels, causing ischaemia and necrosis in the skin and subcutaneous fat. The lesions are usually small but, in extreme cases, may be very extensive and may mimic necrotising fasciitis, prompting extensive surgical debridement. We describe the challenges faced in managing such a case. A 38-year-old female patient was admitted to another hospital with widespread progressive truncal skin necrosis. A provisional diagnosis of necrotising fasciitis was made, and she underwent debridement of 32% of her total body surface area (TBSA). However, her condition rapidly deteriorated and she was transferred to our burn centre for further management. Diagnosis of calciphylaxis was based on clinical features and confirmed by tissue biopsy. Characteristic findings of progressive skin and fat necrosis at the wound margins with healthy underlying fascia and muscle were recognised from previously treated cases of calciphylaxis; however, the absence of renal disease proved misleading. Non-uraemic calciphylaxis is very rare but can, as in this case, be associated with alcoholic liver disease. At our centre, the patient required prolonged ventilation and supportive treatment in burns critical care, combined with intensive wound management, repeated episodes of debridement, temporary wound cover using human skin allografts and reconstruction using split-thickness autograft. We report this case to alert others to this rare condition as a possible diagnosis in patients presenting with extensive panniculitis. We discuss associations, diagnostic difficulties, novel therapies and the importance of multidisciplinary care in managing these complex cases. Level of evidence: Level V, diagnostic study.

There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era.Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient.Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows:Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%.Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and-in selected cases-external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.

Background A burn injury results in the release of proinflammatory cytokines and catecholamines, causing a hypermetabolic state which may lead to hyperpyrexia (>40 °C). This risk is increased with concomitant sepsis. Hyperpyrexia is associated with a high mortality. Continous veno-venous haemodiafiltration (CVVHDF) can be used to reduce the circulating cytokines thereby reducing the cause of the hyperpyrexia. CVVHDF use has been well documented in sepsis and SIRS in the ITU population. In our Burns Centre, CVVHDF is routinely used to treat patients with persistent hyperpyrexia. The aim of this study was to evaluate the role of CVVHDF in burns patients with hyperpyrexia.

Benign metastasizing leiomyoma is a very uncommon clinicopathologic entity with unknown molecular pathogenesis. We present a case of a 40-year-old woman who has a history of surgical resection of a large uterine leiomyoma and then subsequently presented with benign metastasizing leiomyomas to her lungs. Due to her tumor being estrogen receptor (ER) positive and progesterone receptor (PR) positive, she was empirically treated with anastrozole with sustained clinical benefit. Molecular studies with Foundation One testing showed low mutational burden and mutational variants in five known cancer genes. Our findings have important clinical and pathogenetic implication for metastasizing uterine leiomyoma.

Burns to the perineal area and genitals are normally found in the context of widespread burn damage, and are uncommon in isolation. Causes, challenges, and the initial management of genital burns are discussed.

Introduction/Objective Primary tumors of the heart are uncommon; even rarer are primary cardiac neuroendocrine tumors. To our knowledge, only two cases have been described to date, both being high-grade tumors. We report a solitary low-grade neuroendocrine tumor of the heart, unexpectedly discovered on the wall of the right ventricle in a 44-year-old man during aortic valve repair for infectious bacterial endocarditis. Results Frozen section was sent intraoperatively and showed a plasmacytoid neoplasm. Final pathology of the biopsies showed a tumor composed of both cohesive and discohesive plasmacytoid cells separated by a vascular network and strands of fibrosis. Neither necrosis nor a mitotic rate greater than 2 mitoses per 2 mm2 were seen. The tumor showed strong reactivity for AE1/3, synaptophysin and CDX2 with focal reactivity for chromogranin-A and CD56, confirming the diagnosis of a low-grade neuroendocrine tumor. Both an esophagogastroduodenoscopy and colonoscopy were performed and showed no evidence of a primary gastrointestinal tumor. PET-CT DOTATATE performed after complete resection of the tumor showed no abnormal radiotracer uptake. The possibility of an intestinal neuroendocrine tumor undetected by DOTATATE PET-CT with a single known metastasis to the heart was considered. This too, on the basis of the literature, was considered exceedingly rare. Complete resection of this patient’s tumor was considered sufficient treatment; the patient was advised to follow up annually with medical oncology. Conclusion The presentation and management of a solitary cardiac low-grade neuroendocrine tumor has not previously been described in the literature.

Patient: Male, 72-year-old Final Diagnosis: Sarcomatoid carcinoma arising from inverted papilloma Symptoms: Nasal mass • nasal obstruction Medication: — Clinical Procedure: Excsion Specialty: Pathology Objective: Challenging differential diagnosis Background: Carcinosarcoma of the sinonasal tract is an extremely rare malignant neoplasm; it is often designated as carcinoma with spindle cell or sarcomatoid features. We report a case of carcinosarcoma arising in a pre-existing inverted Schneiderian papilloma in the left maxillary antrum and nasal cavity of a 72-year old male patient. Case Report: The patient had a significant history of radiotherapy for squamous cell carcinoma in the sinonasal area, 3 decades ago. The patient presented with chief complaints of left nasal blockage, nasal discharge, anosmia, and occasional epistaxis. Computed tomography scan displayed a lobular soft tissue mass resulting in narrowing of the nasopharyngeal airway with massive destruction of palatal tissue. The lesion was resected via endoscopic surgery. Macroscopically, a white fleshy appearance with necrosis was noted in the submitted specimen. Microscopically, the tumor was composed of pleomorphic epithelial and spindle cells with numerous mitoses and remarkable tissue necrosis. Residual inverted papilloma (IP) with high-grade dysplasia, and minimal foci of moderately differentiated squamous cell carcinoma (SCC) component was present at the tumor margin. A distinct zone of transition of SCC to spindle cell carcinoma (SpSCC) was noted and confirmed by focal positivity of p63 in epithelial and sacromatoid components. The pleomorphic sarcomatoid tumor was positive for vimentin with Ki67 highlighting 70% of tumor cells. A final diagnosis of sinonasal spindle cell carcinoma associated with residual inverted papilloma was rendered. Conclusions: Due to the rarity of such cases, the prognosis and response to treatment is unclear. No effective directed treatment has been developed. Unfortunately, the patient refused any further treatment and died of persistent disease. To the best of our knowledge, only one case of sinonasal carcinosarcoma arising from dysplastic inverted papilloma has been reported. The distinct possibility of previous radiotherapy contributing to development of sarcomatoid features in this neoplasm should also be considered.

Introduction Pericardial involvement of sarcoidosis is a rare cause for acute heart failure, and usually occurs as a result of the development of a pericardial effusion leading to cardiac tamponade. Even rarer still, is the manifestation of constrictive pericarditis. We report a case of sarcoidosis with lung, pleural, and pericardial involvement with effusive-constrictive pericarditis leading to cardiac tamponade. Case presentation A 34-year-old Caucasian man presented for evaluation of a history of worsening exertional dyspnea, edema, and weight loss. A high-resolution chest computed tomography showed diffuse pulmonary nodules with upper lobe predominance and in a perilymphatic distribution; large right pleural effusion; and large pericardial effusion with pericardial thickening. A transthoracic echocardiogram demonstrated early tamponade physiology for which a pericardial drain was placed. After removal of the drain he developed cardiogenic shock from cardiac tamponade attributed to the reaccumulation of a pericardial effusion and urgent pericardial window was performed. Serial echocardiography was concerning for organization and localization of the pericardial fluid. Cardiac magnetic resonance imaging demonstrated a significant reduction in pericardial slippage between the parietal and visceral layers around the heart collectively suggestive of constrictive pericarditis. Confirmation of effusive-constrictive pericarditis was noted on right heart catheterization. He then underwent pericardiectomy, which on histopathologic evaluation demonstrated non-necrotizing granulomas, thus confirming pericardial involvement of sarcoidosis. Conclusions We report a case demonstrating unique manifestations of sarcoidosis; effusive-constrictive pericarditis presenting with acute congestive heart failure.

OBJECTIVE The significance of positive margin in favorable-stage well-differentiated thyroid cancer is controversial. We report outcomes of positive-margin patients with a matched-pair comparison to a negative-margin group. MATERIALS AND METHODS A total of 25 patients with classic-histology papillary or follicular carcinoma, total thyroidectomy +/- node dissection, stage T1-3N0-1bM0, positive surgical margin at primary site, adjuvant radioactive iodine (I-131), and age older than 18 years were treated between 2003 and 2013. Endpoints were clinical and biochemical (thyroglobulin-only) recurrence-free survival. Matched-pair analysis involved a 1:1 match with negative-margin cases matched for overall stage and I-131 dose. RESULTS Recurrence-free survival in positive-margin patients was 71% at 10 years. No patient was successfully salvaged with additional treatment. Only 1 patient died of thyroid cancer. Recurrence-free survival at 10 years was worse with a positive (71%) versus negative (90%) margin (P=0.140). CONCLUSIONS Cure with a microscopically positive margin was suboptimal (71%) despite patients having classic-histology papillary and follicular carcinoma, favorable stage, and moderate-dose I-131 therapy.

Merkel cell carcinoma (MCC) is an uncommon but highly malignant neuroendocrine tumor of the skin. Merkel cell carcinoma can metastasize, but involvement of the central nervous system is rare. Here we report a case of rapidly progressing metastatic MCC to the clivus and bilateral cavernous sinus in an immunocompromised patient. This case is unique in that it is the first case report showing MCC metastasis to the clivus from a distal site. It also demonstrates that a MCC metastasis can masquerade with symptoms of Tolosa-Hunt syndrome. A literature review on MCC with CNS metastasis is presented.

Carcinosarcoma or carcinoma with spindle cell/sarcomatoid features of the nasal cavity and paranasal sinuses is an exceedingly rare malignancy. We report a case of carcinosarcoma with synchronous inverted papilloma developing in the left nasal cavity and maxillary sinus, in a 72-year-old male with a history of radiation therapy for sinonasal squamous cell carcinoma, 30 years ago. The patient's chief complaint was left nasal obstruction. He also reported purulent nasal drainage, impaired sense of smell and occasional epistaxis. CT imaging showed lobular growth of soft tissue narrowing nasopharyngeal airway with extensive palatal erosion. Endoscopic sinonasal surgery was performed to remove the sinonasal mass. Grossly, the tumor had a white fleshy appearance with tumor necrosis. Microscopically, the tumor was composed of pleomorphic epithelial and spindle cells with frequent mitoses and tumor necrosis. Residual inverted papilloma (IP) with high-grade dysplasia, and foci of keratinizing squamous cell carcinoma (SCC) component (2%) was present at the edge of the main tumor. A transition of SCC to spindle cell carcinoma was present confirmed by focal p63 positivity in both components. The pleomorphic sarcomatoid tumor was positive for vimentin and negative for P40, CK5/6, AE1/AE3, p16, S-100, CD34, CD31, ERG1, SMA, desmin, Sox10, and myogenin with Ki67 highlighting 70% of tumor cells. A final diagnosis of sinonasal sarcomatoid carcinoma associated with residual transformation from IP to SCC was rendered. Due to rarity of such a case, the prognosis and response of treatment is uncertain. So far, no effective targeted therapy has been reported. The patient is currently being treated with aggressive chemotherapy. To the best of our knowledge, this is only the second case of sinonasal carcinosarcoma arising from inverted papilloma with high-grade dysplasia and transition to sarcomaitoid SCC. Perhaps the previous radiation therapy played a role in the development of the sarcomatoid variant of SCC.

Bovio I M, Al-Quran S Z, Rosser C J, Algood C B, Drew P A & Allan R W (2010) Histopathology 56, 951–956 Smoothelin immunohistochemistry is a useful adjunct for assessing muscularis propria invasion in bladder carcinoma Aims: To prospectively evaluate the utility of smoothelin immunohistochemical expression for the evaluation of muscularis propria (MP) in diagnostic transurethral resection of bladder tumour (TURBT) specimens and cystectomies. Methods and results: Smoothelin immunohistochemistry was performed on a total of 26 TURBT and cystectomy specimens. All but two cases (24/26) demonstrated strong (3+) or moderate (2+) immunoreactivity of the MP with smoothelin. Muscularis mucosae (MM) never displayed strong (3+) reactivity, and in only one case did the MM have moderate (2+) reactivity; in this case the MP had strong (3+) reactivity. MM intensity mirrored the intensity of reactivity of blood vessels in all cases (26/26). Using moderate or strong immunoreactivity as a cut-off, smoothelin had a sensitivity of 92% for detecting MP and a specificity of 97% for distinguishing between MP and MM. In all unequivocal MP-invasive and lamina proporia-invasive cases by haematoxylin and eosin (H&E), smoothelin immunohistochemistry confirmed the original light microscopic diagnosis. In four cases in which there was equivocal MP involvement by H&E, smoothelin helped establish MP invasion. Conclusions: Smoothelin immunohistochemistry has diagnostic utility in the evaluation of MP invasion in urothelial carcinoma. Smoothelin could be used as an adjunct to traditional H&E-stained light microscopy and may help reduce the number of equivocal diagnoses.

It has been accepted for many years that the cost of care for the burn-injured patient is high. There is, however, little published data to show how "expensive" it is. At the Welsh Centre for burns we have undertaken a costing exercise in an attempt to define the true cost to the treatment of burns. Using our current cost base and activity, we established a cost per health related group (HRG) for burns and also prospectively calculated costs for three inpatients to determine whether HRG-based burn tariffs accurately represent these costs. The NHS is under increasing pressure to provide evidence to support budgetary requirements; we feel this paper offers a framework for burn care costing upon which calculations could be based.

OBJECTIVES We set out to examine our use of the squamous intraepithelial lesion (SIL) category, compare our SIL rate to rates reported by others, and determine the corre-lation between SIL and histologically proven cervical intraepithelial neoplasia (CIN) in our population. MATERIALS AND METHODS Reports from all Papanicolaou smears and associated histological specimens interpreted by the University of Florida Department of Pathology between 1992 and 1996 were reviewed. RESULTS Of 39,484 Papanicolaou smears, 2,101 (5.3%) were classified as low-grade squamous intraepithelial lesion (LGSIL) and 1,366 (3.5%) were classified as high-grade (HGSIL). Of the LGSIL cases, 972 (46.3%) underwent timely biopsy: Findings were benign in 29.9%; 41.7% had CIN1,20.9% had CIN2, and 7.5% had CIN3. Of the HGSIL cases, 932 (68.2%) underwent timely biopsy: Findings were benign in 12.3%; 17.1% had CIN1, 26.7% had CIN2, 42.2% had CIN3, and 1.6% showed squamous cell carcinoma. Condusions. Our LGSIL rate is similar to reported rates, but our HGSIL rate of 3.5% is higher. We found good correlation between SIL on Papanicolaou smear and CIN on biopsy (70.1% for LGSIL and 86% for HGSIL).

Hemangioblastoma primarily occurs in the CNS, most commonly in the posterior fossa. Extracranial locations are less common, and metastatic tumor involving the lung is exceedingly rare with only three cases previously reported. Two were autopsy studies in patients who died of complications of the CNS hemangioblastomas in 1943 and 1981, and the third was mentioned in a case report addendum providing follow-up information on hepatic hemangioblastoma in 1991. We report a case of a 48-year-old man who presented with multiple lung nodules treated by surgical excision. Pathological study revealed features classic for hemangioblastoma. The patient had a remote history of hemangioblastomas having been excised from the posterior fossa 7 and 20 years previously. This report details a fourth case of metastatic pulmonary hemangioblastoma. It is the first report on surgically resected hemangioblastomas from the lung of a living patient with histological and immunohistochemical characterization.

Integra artificial skin provides immediate full-thickness reconstruction for cutaneous burns. The clinical outcome appears to be superior in terms of final function and cosmesis. Consequently the use of such a skin substitute is being heralded as the future treatment of choice, particularly for massive burns where autologous donor skin is limited. The three cases reported here describe the senior author's early experience with Integra and highlight some of the difficulties and successes encountered. A high rate of dermal graft loss and slow epidermal engraftment have tempered the original enthusiasm, but with growing experience the final outcome justifies the continued use of Integra in our unit.

Objective We reviewed consecutive cases classified as benign cellular changes (BCC) over a four-month period. Study design Cases classified as BCC were retrieved from the cytology files. A search was carried out to identify the previous Pap smears and concomitant cervical biopsies. Results One thousand one hundred three cases (23% of our gynecologic smears) were classified as BCC. Ninety-two patients (8.3%) underwent concurrent cervical biopsies. Specific infections accounted for 8% of BCC cases; reactive changes accounted for 92%. Of the biopsy specimens, 8.3% had no significant pathologic change. The most common biopsy diagnoses were cervicitis (31.5%), immature squamous metaplasia (16.3%) and reserve cell hyperplasia (10.8%). Miscellaneous benign diagnoses accounted for 21.7%. Cervical intraepithelial neoplasia (CIN) 1/human papillomavirus (HPV) was present in 14% of cases. All patients with biopsy diagnoses of CIN 1 had at least two previous abnormal Pap smears. Previous biopsy reports were available for review in 127 (12%) of the 1,103 patients. Of these 127 cases, 53.5% had a previous diagnosis of CIN/HPV; 9.4% had invasive carcinoma. A benign diagnosis was reported in 36.5%. Conclusion The majority of BCC cases are due to reactive and inflammatory processes. In patients with a previous history of CIN, BCC may be of some significance. In patients with no significant prior cervical abnormalities, a Pap smear classified as BCC represents a reactive process.

OBJECTIVE: To evaluate the qualification of a Pap smear classified as atypical squamous cells of undetermined significance (ASCUS) favor reactive or neoplasia as recommended by the Bethesda System. STUDY DESIGN: The smears from 105 concurrent patients with a cytologic diagnosis ofASCUS not otherwise qualified were reviewed and subclassified as ASCUS favor reactive, low grade squamous intraepithelial lesion (LSIL) or high grade squantous intraepithelial lesion (HSIL) based on the Bethesda System criteria. The cervical biopsy diagnoses were correlated. RESULTS: Of the 105 cases classified as ASCUS, 37 were subclassified as favor reactive, 51 asfavor LSIL and 17 as favor HSIL on cytologic review. In the ASCUS favor reactive group, 19 (51%) had reactive changes on biopsy, 17 (46%) had cervical intraepithelial neoplasia (CIN) 1, and 1 (2%) had CIN 3. A total of 48% patients had CIN. In the favor LSIL group, there was CIN 1 in 28 cases (55%), CIN 2 or 3 in 12 (23%) and benign changes in 11 (22%) on biopsy. Seventy-eight percent had CIN. In the 17 cases classified as ASCUS favor HSIL group, all had CIN. CONCLUSION: Of the total 105 cases of ASCUS, 71% had CIN, 29% had reactive changes on follow-up biopsies, and 48% of patients in the ASCUS favor reactive group had CIN. Qualifiers of ASCUS have questionable utility in patient management.

The application of modern technology in basic research often requires fresh tissue from human organs. The acquisition of this tissue challenges the anatomic pathologist to balance the needs of the basic scientist with the requirements of quality patient care. Our experience indicates that fresh tissue adequate for research can be obtained from neoplastic prostate glands without compromising patient care. The process requires dedicated, knowledgeable individuals and extensive documentation. Potential problems include low yield for research studies, loss of all residual carcinoma, compromise of the specimen margin, and unforeseen costs. Best collaborations occur in situations in which basic scientists and anatomic pathologists establish a working relationship and develop a mutually supportive means of funding.

Purpose: Androgen deprivation therapy with analogues of luteinizing hormone-releasing hormone produces distinctive histological changes in neoplastic and nonneoplastic prostate tissue. Others have described these features in cases in which treatment status was known. To our knowledge the specificity and sensitivity of luteinizing hormone-releasing hormone effects based only on histology and possible reasons for interobserver variation have not been addressed previously.Materials and Methods: Slides from 97 prostatectomies performed in a 3-year period were reviewed by 2 observers blinded to knowledge of previous hormonal treatment. The observers evaluated each case, recording the presence or absence of 14 features associated with androgen deprivation therapy, and then made an overall assessment regarding treatment status.Results: Of the 97 patients 31 had received androgen deprivation therapy with the luteinizing hormone-releasing hormone agonist leuprolide. A luteinizing hormone-releasing hormone ...

In November, 2012, a 28-year-old man, presented with a 4-day history of fever, shivers, sweating, and vomiting. He had type-2 diabetes, which was being treated with sitagliptin and metformin. On admission he had evi dence of a systemic infl ammatory response (temperature 39·3°C, pulse 160 bpm, respiratory rate 30 per min, white cell count 15·0×10⁹ per L, with 12·3 neutrophils and 0·2 mye locytes), abnormalities of blood clotting (INR 1·6, PTT 57 s, fi brinogen 0·99 g/L (normal range 1·5–4·5); plate lets 19×10⁹ per L), multi-organ failure (creatinine 167 μmol/L, raised alanine aminotransferase 511 U/L and bilirubin 87 μmol/L), progressive hypoxia, hyperglycaemia glucose 20·6 mmol/L), and lactic acidosis (PH 7·29, lactate 7·5 mmol/L). He was diagnosed with overwhelming sepsis and transferred to the intensive care unit. Initial treatment was with piperacillin-tazobactam, insulin, oxygen, and aggressive fl uid replacement, including platelet infusions, fresh frozen plasma, and cryo-precipitate. Ventilatory support was required 15 h after admission, at which time he was anuric. Renal replace-ment therapy was needed for 21 days and ventilatory support for 38 days, partly because of pseudomonas superinfection of the chest that was diagnosed on day 17.Tests for legionella and leptospira and initial blood cultures were negative. Serum taken 30 days after admission had a high IgG titre to Seoul hantavirus (1:10 000 by IFA, Euroimmun, Medizinische Labor-diagnostika AG), although serum from 1 month before admission (sent for hepatitis screening because of a mild transaminasaemia) was negative. Hantavirus RNA was not detected in either sample. We learnt that he kept two pet agouti rats (

Clear cell adenocarcinoma of the lower urinary tract is a rare neoplasm whose histogenesis has not been thoroughly investigated. We have examined six specimens of clear cell adenocarcinomas collected from three institutions using histological, histochemical, and immunohistochemical techniques. Results indicate that almost all clear cell adenocarcinomas of this region express morphological and antigenic features, suggesting müllerian differentiation, and that müllerian differentiation is not a feature of either nonclear cell adenocarcinomas or normal female paraurethral glands. Including the authors' six specimens, 46 specimens have been reported in the available English literature. The accumulated experience confirms the initial impression that these tumors develop predominantly in the urethras of women and occur over a wide age range. Despite high stage at diagnosis, most patients have been alive with no evidence of disease when reported, a prognosis that seems to apply regardless of length of follow-up.

Background. Leuprolide, an agonist of luteinizing hormone-releasing hormone (LH-RH), and flutamide, an antiandrogen, increasingly are being used in the treatment of clinically localized prostate cancer. Only two small series (of 23 and 12 patients) have been published on the distinctive pathologic changes induced in the prostate by androgen deprivation therapy with discrepancies on the presence of squamous metaplasia, necrosis, and possible tumor destruction by combined androgen deprivation therapy. Methods. One hundred and thirteen radical prostatectomy specimens obtained after at least 3 months of leuprolide-flutamide androgen inhibition therapy and 60 nonhormonally treated prostates in randomly selected clinical Stage T2 prostate adenocarcinoma patients were entirely sectioned. Distinctive histologic findings were tabulated and their statistical value determined. Results. Resection margins of excision were involved by tumor in 43% of untreated and in 19% of androgen-deprived patients. Characteristic changes in androgen-inhibited nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layer, and squamous and transitional cell metaplasia. Prostatic intraepithelial neoplasia (PIN) was observed in 35% of treated patients. The presence of small tumor glands separated by stroma was the most frequently noted effect of androgen deprivation on prostate adenocarcinoma; pyknosis and branching empty spaces were less frequent. Large clear tumor cells within an inflammatory response was a third histologic pattern. Apparently unaltered tumor areas were observed in 43% of prostates exposed to androgen deprivation therapy. Conclusions. Androgen deprivation therapy result in histologically distinctive changes that can be recognized in both nonneoplastic and neoplastic prostate tissue. Residual tumor was present in all 113 treated radical prostatectomy specimens. In addition to glandular shrinkage, therapy was associated with statistically significant reductions in the frequency of high grade PIN and extension of cancer to prostate specimen margins of excisions. Cancer 1995;75:1634-41.

Introduction: Globally, many burns units moved away from colloid resuscitation in response to the Cochrane review (1998). Recent literature has introduced the concept of fluid creep: patients receiving volumes far in excess of the upper limit of the Parkland formula. The Cochrane review has been widely criticised, however, and we continued to use 4.5% human albumin solution after 8 h of crystalloid as a hybrid of Parkland and Muir & Barclay’s regime. Methods: Adult patients ⩾15% TBSA were identified from data prospectively entered into our database over a 5-year period (2003–2008). Medical notes and intensive care charts were reviewed comparing volumes of fluids received with requirement estimates. Adverse events were also documented. Results: A total of 72 cases with 34 sets of intensive care charts were analysed. Mean TBSA was 35.2% (range, 15–95%). A total of 75% survived; 3% were haemofiltered. Forty-one percent of patients were resuscitated using the Parkland formula alone, while 59% switched at 8 h post burn to the Muir and Barclay formula (Hybrid group). There was a significantly greater TBSA in the Hybrid group, but they received significantly less fluid volumes than the Parkland group (P = 0.0363; the Hybrid group received 1.36 times calculated need vs. 1.62 in the Parkland group). Conclusion: Our patients still demonstrate fluid creep, but to a lesser extent than previously reported. Fluid creep has been mitigated but not eliminated through this strategy., Lay Summary This article adds to the evidence that major burns patients are receiving higher volumes of fluids than they are estimated to need. This phenomenon is termed ‘fluid creep’ and can have adverse effects. Fluid creep, however, occurred significantly less when albumin was used as part of the regime, even though the patients had more severe burns. There were no adverse events attributable to albumin administration, showing that this is a safe method of mitigating fluid creep. More work, however, needs to be done in this field.

The proliferative activity of invasive squamous cell carcinoma of the vulva was examined using a Ki-67 equivalent monoclonal antibody (MIB1), which gives a strong immunoreaction in paraffin-embedded tissue. Quantitation of Ki-67 immunostaining was accomplished by image analysis. Ki-67 immunostaining revealed two general patterns of reactivity in vulvar tumors: (a) a diffuse distribution of Ki-67 positive nuclei within the tumor mass and (b) a localized distribution of Ki-67 positive nuclei staining predominantly basilar components of tumor aggregates. The distribution of localized and diffuse patterns did not differ significantly between various clinicopathologic categories (age, histologic type and grade, FIGO stage, and lymph node status). However, the survival times for patients with a diffuse Ki-67 labelling pattern tended to be shorter than those for patients with a localized pattern. Survival curves based on the median positive nuclear area (PNA) calculated by image analysis did not differ significantly. Thus, the pattern of Ki-67 immunostaining, rather than the percentage of PNA, may have prognostic significance in vulvar squamous cell carcinoma.

Objective: To highlight the key differences in history, examination, and management of pyoderma gangrenosum and necrotizing fasciitis and to outline the importance of distinguishing these 2 conditions. Method: We present a case report of a gentleman with a background of ulcerative colitis having a 1-week history of an erythematous wound and localized abscess to the right leg that failed to respond to antibiotic treatment and later on to surgical debridement of a presumed necrotizing fasciitis. Following referral to our plastic surgery unit, a diagnosis of pyoderma gangrenosum was made and this was confirmed following a response to steroid therapy within 48 hours. A literature review of pyoderma gangrenosum cases misdiagnosed for necrotizing fasciitis was carried out to compare and contrast pitfalls in misdiagnosing these 2 conditions. Results: Literature review of 10 cases confirmed the association of pyoderma gangrenosum with inflammatory bowel disease, hematological disease, and surgical trauma. The presence of necrotic tissue in a pyoderma gangrenosum lesion can be a diagnostic pitfall; although blood and tissue culture investigations are usually negative in pyoderma gangrenosum, this may not always be the case. Inflammatory markers can be significantly high in pyoderma gangrenosum and pyrexia is not a feature limited to necrotizing fasciitis. Conclusions: Inappropriate surgical debridement of pyoderma gangrenosum can cause rapid extension of the lesion by enhancing the posttraumatic response and lead to potential reconstructive challenges with psychological repercussions. On the contrary, treating necrotizing fasciitis with immunosuppressive therapy may worsen the condition. The importance of understanding the pathogenesis, clinical features, and management of both conditions cannot be overemphasized.