Evidence Of Perineural Invasion Research Articles

Microsatellite Instability in Sporadic Colorectal Malignancy: A Pilot Study from Northern India.

Background:Three molecular pathways are described as the genetic basis of colorectal tumorigenesis. Among these, microsatellite instability (MSI) has shown greatest promise in serving as a biomarker to determine disease aggression by tumour biology, recurrence, and response to chemotherapy. Methodology:This prospective observational pilot study included patients of colorectal cancers, in a population subset coming to a tertiary care hospital in northern India, who were operated with curative or palliative intent over a period of one year and followed up for a maximum of 55 months. The post-operative pathological assessment was done for MSI status using PCR technique, and an attempt was made to evaluate its correlation with conventional clinical and histological parameters, early recurrences, disease-free survival and overall survival in comparison to MSS type tumours in sporadic cases of colorectal malignancies. Results:Out of 38 patients of colorectal cancer, 26 were included in the study. Male to female ratio was 7:6 (n=14:12). Mean age of presentation was 48±14.2 years. Incidence of MSI was n=4 (15.4%). On subgroup analysis, age of presentation (p=0.044) and evidence of perineural invasion (p=0.017) was found to have significant statistical association with MSI tumour biology. Recurrence was seen in seven of the seventeen patients who previously had no synchronous or metastatic disease (41.2%). The mean disease-free survival for MSS was 21.32 months and was 25.25 months for MSI group which was statistically insignificant (p = 0.277). Out of four MSI tumour biology patients one was alive and without recurrence at 47 months. While the other two were alive and without recurrence till 27 months of follow-up. Conclusion:Age and perineural invasion showed statistically significant association with MSI tumour biology. Due to the small sample size statistical significance was not established with site, recurrence rate, DFS and OS.

Carcinoma Expleomorphic Adenoma of the Lacrimal Gland.

To report the characteristics and long-term outcomes of patients presenting with carcinoma ex-pleomorphic adenoma (CXPA) or malignant mixed tumor of the lacrimal gland. A retrospective case-note review for patients with CXPA, seen at Moorfields Eye Hospital between 1985 and 2018, was performed for demographics, presentation, imaging, histopathology, management, and outcome. Twenty-six patients (11 male; 42%) presented at a mean age of 46 years (median 46.4; range 24-81), with average symptom(s) duration of 67 months (median 24 months; range 6 weeks-53 years). The commonest symptoms were proptosis (13 patients; 50%), orbital ache or pain (11/26, 42%), having noted a lump in the upper eyelid (8/26, 31%), and diplopia (7/26, 27%). About 90% of patients had nonaxial globe displacement, over a half had a palpable mass and 3-quarters had reduced motility. Adenocarcinoma was the commonest malignant component of the tumor, occurring in 16 (62%) of the patients, followed by adenoid cystic carcinoma in 5 patients (19%); 10/26 (28%) tumors showed significant invasion on histological examination. A quarter of the patients had tumor-related death at an average of 2.8 years after diagnosis (median 2.5; range 1.5-4.4 years), and the overall probability of survival for the whole cohort was 63% at both 5 years and 10 years after treatment. The prognosis for CXPA was significantly worse with a history of prior incompletely excised pleomorphic adenoma (p < 0.001), a markedly invasive malignant component (p = 0.001), evidence of perineural invasion (p = 0.042), and an American Joint Committee on Cancer tumor size of T3 or greater (p = 0.024). Intact excision of CXPAs that do not display histological evidence of extension beyond the tumor pseudocapsule have a good outcome, similar to that for intact excision of benign pleomorphic adenomas. In contrast, our patients with markedly invasive CXPA had a tendency to local recurrence or distant metastasis, and tumor-related death occurred in about two-thirds.

Adenoid cystic carcinoma of palate: A rare case report

A 40-year-old female patient reported to the department with the complaint of a single growth and pain in the upper right back tooth region for 1 year. Intraoral examination revealed a single unilateral exophytic growth seen on the right upper pterygomandibular raphe region. Extraoral examination revealed no facial asymmetry and no evidence of lymphadenopathy. Histopathological examination revealed a hyperparakeratotic stratified squamous epithelium of variable thickness with broad and flattened rete ridges. Lesional tissue showed large sheets of cells surrounded by condensed collagen component. The lesional cells were basaloid in appearance with hyperchromatic nucleus predominately arranged in a cribriform pattern along with eosinophilic material. No evidence of perineural invasion was observed in serial sections. On the basis of these findings, the diagnosis of adenoid cystic carcinoma was established.

Perineural invasion (PNI) in vulvar carcinoma: A review of 421 cases

ObjectivesTo evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI). MethodsA retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI. ResultsOf the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p < 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range < 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p < 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p < 0.001; PFS: hazard ratio, 1.64; p-value = 0.020). ConclusionPNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.

Abstract B13: Perineural invasion in Ewing sarcoma—a novel mechanism and new therapeutic opportunities

Abstract Tumor dissemination and relapse are the major problems in Ewing sarcoma (ES) treatment, yet the mechanisms driving these processes are unknown. To elucidate the routes of ES metastatic spread, we used an orthotopic xenograft model. ES cells were injected into the gastrocnemius muscles of SCID/beige mice. Once the primary tumors reached the desired volume, they were excised by limb amputation. Subsequently, tumor dissemination was monitored by MRI and confirmed by histopathologic analysis. Interestingly, aside from typical hematogenous metastases, such as bone and lung lesions, we have also observed frequent perineural tumor dissemination manifested by the presence of migratory ES cells along the nerves adjacent to the primary tumors. This phenomenon was associated with formation of recurrent tumors at the amputation sites, as well as pelvic tumors with spine involvement. Interestingly, the level of perineural invasion (PNI) was dependent on the expression of neuropeptide Y (NPY) in ES cells. NPY is a neuronal protein released from peripheral sympathetic neurons, but also highly expressed in ES cells along with its receptors. The xenografts derived from ES cell lines not releasing endogenous NPY (TC71, TC32) exhibited frequent PNI in tumor-bearing limbs, as well as a high number of recurrent tumors at the surgery site and spine metastases (70% and 100% of mice with evidence of PNI for TC71 and TC32 xenografts, respectively). This phenomenon was less common in ES xenografts derived from NPY-rich SK-ES1 cells (17% of mice with signs of PNI). In line with these observations, NPY knockdown in SK-ES1 xenografts drastically accelerated formation of spinal tumors (60% of mice). Notably, in 40% of mice bearing SK-ES1/NPY shRNA xenografts the spinal tumors developed before the primary tumor growth was detectable at the site of ES cell injection. Thus, our in vivo experiments suggested that a lack of endogenous NPY in ES cells expressing high levels of its receptors triggers chemotactic effects of this peptide released from neighboring peripheral nerves, facilitating PNI. Indeed, in a transwell migration assay, NPY exerted significant chemotactic activity in SK-ES1/NPY shRNA cells, but not in the original SK-ES1 cell line. An even more profound chemotactic effect specific to the SK-ES1/NPY shRNA cells was observed with NPY-rich conditioned media obtained from neuroblastoma cells, which can serve as a model of peripheral sympathetic neurons. Further studies are required to determine which NPY receptors are responsible for its chemotactic properties. If the presence of perineural tumor growth is confirmed in human tumors, factors responsible for PNI in ES, e.g., NPY receptors, may become targets for novel therapies preventing disease dissemination and recurrence. Citation Format: Susana Galli, Sung-Hyeok Hong, Jason U. Tilan, Mina Adnani, Shiya Zhu, Yassi Fallah, Yi-Chien Lee, Olga Rodriguez, Chris Albanese, Ewa Izycka-Swieszewska, Joanna Kitlinska. Perineural invasion in Ewing sarcoma—a novel mechanism and new therapeutic opportunities [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B13.

A Novel Classification and Staged Approach for Dissection Along the Celiac and Hepatic Artery During Pancreaticoduodenectomy

In recent decades, there have been enthusiastic discussions of, and active proposals for, new approaches to dissection around the superior mesenteric artery during pancreaticoduodenectomy (PD). In contrast, dissection along the celiac axis (CA) and hepatic artery (HA) and in the hepatoduodenal ligament has rarely been systematically discussed. In this report, we propose and describe a three-level classification of dissection along the CA-HA system which is applicable to a variety of diseases for which PD is indicated. The extent of dissection is classified into three levels. With the first level (LV-1), neither LN nor plexus dissection is required. The second level (LV-2) includes en bloc resection of LNs along the CA, HA, and in the hepatoduodenal ligament, preserving the nerve plexus around the artery. The third level (LV-3) includes en bloc dissection of LNs and the nerve plexus close to cancer invasion, for example, being accompanied by half circumferential dissection of the nerve plexus around the CA or circumferential dissection of that of HA. LV-1 dissection is indicated for benign lesions, low grade malignancy, pancreatic metastasis, or intraductal papillary mucinous neoplasm. LV-2 is indicated for periampullary malignancies requiring dissection of regional LNs, including ampullary, distal bile duct, duodenal cancers, and pancreatic cancers without evidence of invasion around the CA-HA system. LV-3 is indicated for malignancies with evidence of perineural invasion in the CA-HA system, such as pancreatic cancer at the pancreatic neck or advanced bile duct cancer. In combination with classified superior mesenteric artery dissection, a variety of PD procedures would be systematically classified, understood, and reproduced regardless of nature of disease, surgeon, or approach.

Basal cell carcinoma missed by deep shave biopsy: A sampling error

An 85 year old Caucasian male with no history of immunosuppression presented with an asymptomatic bump on his left lateral neck which was present for several weeks. Physical examination revealed 1.0 cm × 0.8 cm flesh colored soft nodule associated with an underlying well healed scar on the left lateral neck. He had a nodular basal cell carcinoma (BCC) without any evidence of perineural invasion which was removed by a wide local excision with 4 mm margins in the area of the scar on the left lateral neck 14 months earlier. The results of that excision had revealed clear surgical margins. The area had healed well post operatively without any complications. Patient requested a biopsy of the bump because he was convinced that the bump represented a recurrence of his BCC. A deep frozen section biopsy of the bump was performed which revealed scar tissue with no evidence of any malignancy. The biopsy tissue from the frozen section was then submitted for permanent section processing in formalin which also showed the same diagnosis of scar tissue with no evidence of malignancy Patient was informed of the results but he insisted on having further resection of the lesion as he was still convinced that the lesion is cancerous. He then underwent a deeper excision of the same area which revealed basal cell carcinoma. Patient subsequently underwent Mohs micrographic surgery for more definitive treatment which required 3 stages. During the first stage of Mohs surgery, the top portion of the slide revealed only scar tissue and positive basal cell margin was at the very deep margin with only a small focus of tumor present. Subsequent Mohs stage revealed larger areas of basal cell carcinoma extending deeper into the neck tissue. This case illustrates that a negative skin biopsy report does not always rule out skin cancer. Clinical judgment and high index of suspicion especially in high risk individuals is essential in making accurate diagnosis of skin cancers. Relying solely on laboratory testing such as a skin biopsy slide alone may not be adequate and further tissue examination maybe necessary in cases of recurrent basal cell carcinoma.

Adjuvant chemotherapy in elderly patients with pancreatic cancer

Background:Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer.Methods:We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative.Results:The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ⩾70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8% P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27–2.78, P=0.002).Conclusion:Patients aged ⩾70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.

Evidence of Perineural Invasion on Prostate Biopsy Specimen and Survival After Radical Prostatectomy

To better understand relationships between perineural invasion (PNI) and radical prostatectomy outcomes, we examined whether PNI was independently associated with adverse pathologic features and worse survival outcomes after radical prostatectomy. PNI is a routinely reported pathologic parameter for prostate biopsy specimens. We identified 3226 patients undergoing radical prostatectomy for clinically localized prostate cancer at our institution between 1994 and 2010. We used multivariable logistic regression models to examine whether PNI was independently associated with extraprostatic extension, seminal vesicle invasion, and surgical margin status. We used Kaplan-Meier methods and the log-rank test to assess disease-free, prostate cancer-specific, and overall survival according to PNI status. Cox proportional hazards modeling was used to evaluate relationships between PNI and survival outcomes. PNI was identified in the prostate biopsy specimen in 20% of patients who underwent radical prostatectomy. Patients with PNI were more likely to have adverse pathologic features, including extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Patients with PNI had shorter disease-free, cancer-specific, and overall survival (all log-rank P <.001). After adjustment for adverse pathologic features at radical prostatectomy, PNI was independently associated with disease-free survival (adjusted hazard ratio, 1.45; 95% confidence interval, 1.09-1.92) and overall survival (hazard ratio, 1.57; 95% confidence interval, 1.13-2.18). PNI was independently associated with adverse pathologic features and worse survival outcomes after radical prostatectomy. For these reasons, PNI on prostate biopsy specimens should be considered in prostate cancer treatment decision making and clinical care.

Evidence of Perineural Invasion on Prostate Biopsy Specimen and Survival After Radical Prostatectomy

Evidence of Perineural Invasion on Prostate Biopsy Specimen and Survival After Radical Prostatectomy

Prognostic implications of perineural invasion following radical cystectomy for urothelial carcinoma.

e15014 Background: Perineural invasion(PNI) with urothelial carcinoma may be identified in radical cystectomy specimens, and its prognostic significance is controversial. We sought to determine the incidence and prognostic implications of PNI in a cohort of patients undergoing radical cystectomy for primary bladder cancer. Methods: From January 1996 to June 2011, 440 patients underwent radical cystectomy for urothelial bladder cancer with curative intent. Presence of PNI was determined in the cystectomy specimens, in addition to other histopathologic variables (grade, stage, surgical margins, lymphovascular invasion, concomitant variant secondary histologic subtypes, and presence of carcinoma-in-situ). Recurrence and survival data were analyzed to determine the prognostic significance of PNI in this cohort. Results: PNI was identified in 101 patients (23%) in our series. Those with extravesical primary tumors (61/128, 48%) and node-positive disease (34/86, 40%) were more likely to have PNI than organ-confined tumors (&lt;pT2; 10/183, 5%) (p&lt;0.001). Median follow-up was 2 years (range: 0.1 to 12.5 years). Compared to those with no evidence of PNI, recurrence-free survival was worse in the PNI-positive extravesical (p=0.01) and node-positive (p=0.02) tumors. Overall survival was also worse for PNI-positive patients (p&lt;0.001). On multivariate analysis, PNI was an independent risk factor for recurrence after radical cystectomy (p=0.01, RR=2.8: 95% CI 2.0-10.0). In the setting of PNI, adjuvant chemotherapy significantly improved overall survival(p=0.01). When analyzing PNI and lymphovascular invasion(LVI), there appears to be a worse recurrence-free survival for those who have both PNI and LVI than those with either alone(p&lt;0.001). Conclusions: PNI with urothelial carcinoma may be associated with a worse prognosis, especially for extravesical and node-positive disease following radical cystectomy. Adjuvant chemotherapy may benefit those patients who have PNI. Patients who have both PNI and LVI may be at higher risk for disease recurrence.

Perineural Invasion After Preoperative Chemotherapy Predicts Poor Survival in Patients With Locally Advanced Gastric Cancer

We examined gene expression profiles and clinicopathologic features (tumor location, stage, graded pathologic response, perineural invasion (PNI), Lauren's classification, and survival) of patients with gastric cancer who received preoperative chemotherapy to identify prognostic markers. Thirty-eight patients with locally advanced gastric cancer received preoperative chemotherapy on a phase II trial. Twelve fresh-frozen tumor samples were available for RNA expression analysis. Differential gene expression between tumors with and without PNI was identified and correlated with clinicopathologic features. Preliminary hierarchical clustering suggested a separation between long- and short-term survivors. The close association between PNI and overall survival was identified and validated immunohistochemically in 31 completely resected gastric tumors. Five-year survival for patients with PNI and without PNI was 5% and 65%, respectively (P < 0.01). PNI added significant prognostic value to posttreatment pathologic stage, (P < 0.01). Differential gene expression profile for PNI and non-PNI tumors identified 111 potentially relevant genes. Our results demonstrate that the presence of PNI after preoperative chemotherapy is associated with poor survival. These results need to be validated in prospective studies, to help establish whether patients with evidence of PNI would be candidates for more aggressive therapy or enrollment into clinical trials. The presence of PNI provides additional prognostic importance to posttreatment pathologic stage and may indicate treatment resistance. Understanding the molecular events associated with PNI, may provide insight into new therapeutic agents for this subset of patients with resistant tumors.

A rare case of intra-cardiac metastasis from an appendiceal carcinoid tumour without liver metastases

Metastatic tumours to the heart are more common than primary cardiac neoplasms and can occur in as many as 1.5% of patients with malignancies. The most common primary tumours that metastasise to the heart are breast, lung and malignant melanoma. The cardiac tissue most frequently affected is the myocardium, followed by the pericardium and then the endocardium. Metastatic tumours extending into the heart chambers and conducting system are less common. The most common route of metastasis is through lymphatic spread, followed by haematogenous dissemination. Carcinoid metastases to the heart are extremely rare, and only 19 cases have been described in the literature over the past 30 years. These invariably occur in the presence of liver metastases. We present a unique case of a patient who, at post-mortem, was found to have intra-cardiac carcinoid metastases involving a sensitive cardiac structure, in the absence of liver or any other metastases. A 51-year-old white woman presented with a 3-month history of central abdominal pain, nausea, lethargy and malaise. She had previously undergone lapararoscopic cholecystectomy and was prescribed hormone replacement therapy and anti-depressant medication. She denied a history of alcohol misuse, previous blood transfusions or risk factors for hepatitis. Clinical examination was unremarkable; liver function tests were shown to be abnormal (raised gamma-glutamyl transferase and alkaline phosphatase). Abdominal ultrasound showed an echogenic pattern suggestive of metastatic disease, with cirrhosis a less likely possibility. Abdominal and chest computed tomography scan revealed a small (<5 mm) lesion in the left lobe of the liver possibly representative of metastatic disease. Retro-peritoneal lymphadenopathy was also noted, with enlarged lymph nodes seen in the porta hepatis and para-aortic regions. A small right pleural effusion was also seen. No obvious primary lesion was identified. Upper and lower gastro-intestinal endoscopy were inconclusive for a primary neoplastic lesion. Her symptoms worsened with increased abdominal distension, shortness of breath and clinical ascites. Radiological biopsy of the paraaortic lesions was not feasible, and she proceeded to a diagnostic laparoscopy and biopsy. At laparoscopy, a mass lesion involving the appendix and terminal ileum with omental caking and peritoneal deposits was found. The procedure was converted to a laparotomy: An appendicectomy and palliative bypass were performed. A liver biopsy was also carried out. Histology revealed a carcinoid tumour in the appendix with infiltration into mesoappendiceal fat and evidence of perineural invasion. The liver wedge biopsy showed diffuse granulomatous inflammatory change but no evidence of malignancy. Two weeks after surgery, the patient suffered a sudden cardiac arrest. Cardiopulmonary resuscitation was performed, with restoration of pulse at 55 bpm but no blood pressure. An electrocardiogram showed left bundle branch block. The family declined any life-sustaining measures, and the patient passed away shortly afterwards. A post-mortem was carried out, which revealed the presence of Hodgkin’s lymphoma in both the liver and retroperitoneal nodes. No evidence of carcinoid involveInt J Colorectal Dis DOI 10.1007/s00384-009-0709-z

Keratoacanthoma with perineural invasion: An indicator for aggressive behavior?

Neurotropic invasion of keratoacanthoma (KA) is rare and can easily be missed histologically. A 36-year-old woman developed a KA on the upper lip four weeks after CO(2) laser skin resurfacing; it showed microscopic evidence of perineural invasion. Despite repeated treatment with intralesional methotrexate, the KA recurred after 6 months. She was then treated with ionizing radiation (56 Gy) and has been tumor-free for more than 3 years. Immunohistochemistry showed decreased expression of desmoglein 1 as it is seen in squamous cell carcinomas. In most cases not much importance is attached to perineural invasion which is frequently seen in KA because of the high rate of spontaneous regression. Our case suggests that perineural invasion may be an indicator for aggressive growth of head-and-neck KAs so that histologically-controlled excision is recommended.

Skin Cancer of the Head and Neck With Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.

Surgical Management of Locally Advanced Adenoid Cystic Carcinoma of the Lacrimal Gland

To review our experience with multidisciplinary surgical management of locally advanced adenoid cystic carcinoma of the lacrimal gland. We present a case series of 7 patients with lacrimal gland adenoid cystic carcinoma treated at our institution between June 2001 and October 2003. Clinical records, histologic sections, and radiographic images were reviewed. The study included 3 men and 4 women (mean age at diagnosis, 44 years). All 7 patients underwent an orbital exenteration with bone removal. Five patients had an orbitectomy through a craniotomy approach and 2 patients had an exenteration through a fronto-orbito-zygomatic approach, all with removal of the bone of the superior and lateral wall. Six patients underwent reconstruction of the socket through the use of a vascularized flap. The surgical approach involved a neurosurgeon, an oculoplastic or head and neck surgeon, and a plastic surgeon. Six patients received postoperative radiation therapy. One patient with a recurrent tumor had already received radiation therapy, which precluded additional radiation therapy after surgical resection. The radiation field included the orbit and the skull base because all patients had evidence of perineural invasion. As of this writing, there have been no local recurrences. Five patients had development of distant metastases and died of disease, at follow-up times from 12 to 32 months after surgery. Two patients are alive without evidence of disease, both at 24 months' follow-up. Orbitectomy with bone removal may be indicated for achieving local and regional control in advanced cases of adenoid cystic carcinoma of the lacrimal gland. This surgery does not decrease the risk of distant metastasis. The cases in our series highlight the locally invasive and metastatic behavior of this cancer.

Will MAC be back?

Microcystic adnexal carcinoma (MAC) was first described as a specific entity in 1982 by Goldstein et al. MAC is a very aggressive tumour, displaying locally invasive tendencies with perineural invasion. For this reason previous studies have suggested that Mohs micrographic surgery is a superior technique in establishing clear margins of excision. However, there is no evidence to suggest that standard local excision is less effective in achieving tumour clearance or a more favourable outcome. All patients with MAC were identified from the pathology database. All patients who had undergone local excision were reviewed and included in the study. Histopathology was reviewed by dermatopathologists. We reviewed the outcome of 17 patients treated with local excision. Eleven were female and six were male with a mean age of 70 years, and a mean follow up of 30 months. Two patients in this series experienced recurrence after standard local excision. The mean lateral and depth margins were 7.69 mm (range 0.2-21) and 4.66 mm (range 1-14.5), respectively. Recurrence occurred in two out of three patients who had lateral clearance margins of less than 4 mm. These two patients had evidence of perineural invasion on histopathology. In the present study, standard local excision is shown to be effective in tumour clearance for MAC with no recurrences provided there are lateral margins of at least 4 mm. However, a longer period of follow up is required because of the very aggressive locally invasive nature of the tumour.

Skin cancer of the head and neck with clinical perineural invasion

Purpose: To review treatment and outcomes in 62 patients with clinical and/or gross evidence of perineural invasion from skin cancer of the head and neck. Methods and Materials: Sixty-two patients received radiotherapy at the University of Florida as part or all of their treatment between January 1965 and April 1995. All patients had clinical signs and symptoms of perineural involvement and/or documentation of tumor extending to grossly involve nerve(s). Twenty-one patients underwent therapy for previously untreated lesions, including 12 who received radiotherapy alone and nine who had surgery with postoperative radiotherapy. Forty-one patients underwent therapy for recurrent lesions, including 18 treated with radiotherapy alone and 23 who received preoperative or postoperative radiotherapy. Results: Factors on multivariate analysis that predicted local control included patient age, previously untreated vs. recurrent lesions, presence of clinical symptoms, and extent of radiotherapy fields. Recurrence patterns were predominantly local; 26 of 31 patients (84%) who developed local recurrence after treatment had recurrent cancer limited to the primary site. Conclusions: Many patients with skin cancer and symptomatic perineural invasion have disease that is incompletely resectable. Approximately half these patients will be cured with aggressive irradiation alone or combined with surgery. Age, prior treatment, and clinical symptoms influence the likelihood of cure.

Perineural invasion and Gleason 7-10 tumors predict increased failure in prostate cancer patients with pretreatment PSA

Purpose: It has been well established that prostate cancer patients with pretreatment PSA<10 ng/ml enjoy excellent bNED control when treated with definitive external beam radiation therapy. This report identifies predictors of failure for patients with pretreatment PSA <10 ng/ml. These predictors are then used to define favorable and unfavorable prognostic subgroups of patients for which bNED control is compared. Methods and Materials: Between 3/87 and 11/94, 266 patients with T1-T3NXM0 prostate cancer and pretreatment PSA values <10 ng/ml were treated with definitive external beam radiation therapy. Median central axis dose and median follow-up for the entire group was 72 Gy (63–79 Gy) and 48 months (2–120 months). Predictors of bNED control were evaluated univariately using Kaplan-Meier methodology and the log-rank test and multivariately using Cox proportional hazards modeling. Covariates considered were pretreatment PSA, palpation stage, Gleason score, presence of perineual invasion (PNI) and central axis dose. Independent predictors based on multivariate results were then used to stratify the patients into two prognostic groups for which bNED control was compared. bNED failure is defined as PSA ≥ 1.5 ng/ml and rising on two consecutive determinations. Results: Univariate analysis according to pretreatment and treatment factors for bNED control demonstrates a statistically significant improvement in 5-year bNED control for patients with Gleason score 2–6 vs. 7–10, patients without evidence of perineural invasion (PNI) vs. those with PNI, and patients with palpation stage T1/T2AB vs. T2C/T3. Multivariate analysis demonstrates that Gleason score (p = 0.0496), PNI (p = 0.0008) and palpation stage (p = 0.0153) are significant independent predictors of bNED control. Based on these factors, patients are stratified into a more favorable prognosis group (Gleason 2–6, no PNI, and stage T1/T2AB, n = 172) and a less favorable prognosis group (Gleason 7–10 or PNI or T2C/T3, n = 94). A comparison of the two groups reveals that bNED control is significantly lower in the less favorable prognosis group (74% vs. 91% at 5 years, p = 0.0024). Conclusions: (1) This report identifies Gleason 7–10 and the presence of PNI as well as palpation stage T2C/T3 as factors that predict worse bNED outcome for patients with pretreatment PSA < 10 ng/ml who are treated with radiation therapy alone. (2) Patients with these pretreatment prognostic factors may benefit from adjuvant therapies or altered treatment programs. (3) In order to make fair comparisons between radiation therapy and prostatectomy series, the distribution of perineual invasion and Gleason 7–10 must be taken into account.