Differentiating Intrarenal Ectopic Adrenal Tissue From Renal Cell Carcinoma in the Kidney.

BACKGROUND: Adrenal rest (AR) is the presence of ectopic adrenal cortical tissue, often identified incidentally during autopsy (20% of postmortem examination). In the kidney, AR can be found in 6% of the general population. Ectopic adrenal tissue is of no functional significance but may in some cases, pose a diagnostic challenge for the pathologist, especially in the context of renal clear cell renal cell carcinoma (RCC) and small needle biopsies. AIM: To investigate the utility of immunohistochemical stains in distinguishing AR from RCC. METHODS: Archival cases of AR, in our institution, were reviewed and compared with a cohort of RCC cases using a panel of immunohistochemical stains, including PAX2, PAX8, calretinin, and inhibin. RESULTS: Nine of 10 (90%) cases of AR showed positive staining for inhibin and negative staining for calretinin, PAX2 and PAX8. One AR case was positive for PAX2 and PAX8 in addition to inhibin. All (100%) RCC cases were positive for PAX2 and PAX8, but negative for inhibin and calretinin. CONCLUSIONS: A panel of PAX2, PAX8 and inhibin may be useful markers for distinguishing AR from RCC. Calretinin was noncontributory in our study.

Diagnosing bone lesions: a practical non-pathology centric formulaic approach.

Bone lesions are perceived to be some of the most difficult lesions that pathologists encounter. The reasons for this are multiple and include lack of experience/familiarity, the need to rely heavily on non-pathology information and data, and the fact that many lesions are associated with either procedures or treatments with significant morbidity. However, in fact, the majority of bone lesions can be accurately assessed on the basis of data not directly related to traditional pathologic based assessment. In order to achieve this state, the pathologist must understand the consistent clinical parameters of most bone lesions, including their clinical presentation, the bone involved, particularly the anatomic site of the bone involved, and a fundamental, basic understanding of imaging studies, especially the plain radiograph. Once these principles are understood and mastered, the pathologist can easily diagnose most bone lesions, using traditional pathologic assessment to confirm the diagnosis.

Cartilage-forming tumors.

Cartilage-forming tumors as a group are the most common primary bone tumors; this is largely due to the common occurrence of asymptomatic benign lesions such as osteochondroma and enchondroma. The common feature of these tumors is the presence of chondrocytic cells and the formation of cartilaginous tumor matrix. Some of these tumors are true neoplasms while others are hamartomas or developmental abnormalities. The morphologic heterogeneity of these tumors may be explained by a common multipotent mesenchymal cell differentiating along the lines of fetal-adult cartilage maturation. Recently mutations in IDH1 and IDH2 have been detected in a variety of benign and malignant cartilaginous tumors.(1-4.)

Secondary chondrosarcoma of the pelvis arising from a solitary exostosis in an 11-year-old patient: a case report with 5-year follow-up.

Although conversion of an osteochondroma to chondrosarcoma is a well-described rare occurrence, it is usually associated with syndromes such as multiple hereditary exostoses and is much more common after maturity. We present here a rare case of secondary pelvic chondrosarcoma arising from a solitary exostosis in a pediatric patient. An 11-year-old, otherwise healthy, female was referred to our clinic for evaluation of a pelvic mass detected on a radiograph. The radiographs obtained by the referring physician demonstrated a large lesion arising from the right superior pubic ramus, which was visible but not identified on an abdominal radiograph several years prior. Histopathologic analysis showed chondrosarcoma which was supported by an additional opinion to rule out chondroblastic osteosarcoma. The patient was treated with wide resection without adjuvant therapy and is doing well with no evidence of recurrence five years post-operatively. There have been only a few small case series describing chondrosarcoma in the pediatric patient. Even rarer are descriptions of secondary chondrosarcoma with only occasional cases reported as part of larger case series. Chondrosarcoma is a rare and difficult diagnosis in the pediatric patient. There is often considerable debate between chondrosarcoma and chondroblastic osteosarcoma, and the treatment implications of differentiating these diagnoses are of paramount importance.

Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients.

AIM: To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy. METHODS: We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010. Data analyzed consisted of demographic and clinical variables. The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test(®). RESULTS: One hundred and forty two patients were reviewed. Median age was 64 years (36-86 years). Eighty eight patients (62%) received neoadjuvant chemoradiotherapy. Pathological complete and partial responses were achieved in 17 (19%) and 71 (81%) patients. Cancer relapsed in 43/142 (30%) patients. The brain was the first site of relapse in 9/43 patients (21%, 95% CI: 10%-36%). HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9 (56%) cases overexpressed HER-2 (3+ staining). CONCLUSION: HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy. Further studies will be required to validate this observation.

Consensus statement on effective communication of urgent diagnoses and significant, unexpected diagnoses in surgical pathology and cytopathology from the College of American Pathologists and Association of Directors of Anatomic and Surgical Pathology.

CONTEXT: Recognizing the difficulty in applying the concept of critical values to anatomic pathology diagnoses, the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have chosen to reevaluate the concept of critical diagnoses. OBJECTIVE: To promote effective communication of urgent and significant, unexpected diagnoses in surgical pathology and cytology. DESIGN: A comprehensive literature search was conducted and reviewed by an expert panel. RESULTS: A policy of effective communication of important results in surgical pathology and cytology is desirable to enhance patient safety and to address multiple regulatory requirements. CONCLUSIONS: Each institution should create its own policy regarding urgent diagnoses and significant, unexpected diagnoses in anatomic pathology. This policy should be separate from critical results or panic-value policies in clinical pathology, with the expectation of a different time frame for communication. Urgent diagnosis is defined as a medical condition that, in most cases, should be addressed as soon as possible. Significant, unexpected diagnosis is defined as a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient's course. Further details of this statement are provided.

Leiomyosarcoma of the head and neck: a population-based analysis.

OBJECTIVES: To describe the characteristics of head and neck leiomyosarcoma and to identify factors associated with survival. DESIGN: Retrospective population-based study. PATIENTS: The 17-registry Surveillance, Epidemiology, and End Results database was used to identify 578 patients with leiomyosarcoma of the head and neck. INTERVENTIONS: Surgery and primary and adjuvant radiotherapy. MAIN OUTCOME MEASURES: Patient demographics and tumor characteristics were examined. Treatment modalities were compared, and survival was assessed using the log-rank test. RESULTS: The mean age at diagnosis was 64 years. Most tumors were smaller than 5 cm in greatest dimension (87%) and high grade (44% were moderately differentiated and 39% were poorly differentiated). The primary tumor demonstrated deep extension in 39% of cases, and 2% had lymph node metastases. The most common primary site was the skin and soft tissue of the head and neck (83%). Surgical treatment was provided to 89% of patients, 14% received adjuvant radiotherapy, and 4% received radiotherapy alone. The median observed survival was 84.7 months. The 5-year disease-specific survival rate was 87.6% in patients with well-differentiated tumors, 85.7% in patients with moderately differentiated tumors, and 52.7% in patients with poorly differentiated tumors (P < .001). Survival was better for patients who received surgery alone (median survival, 100.1 months [n = 413]) than for those who received radiotherapy alone (median survival, 16 months [n = 16]) or adjuvant radiotherapy (median survival, 64.2 months [n = 80]) (P < .001). The latter group was more likely to have poorly differentiated, large, locally invasive tumors. CONCLUSIONS: Leiomyosarcoma typically presents in older patients; it is often poorly differentiated; and improved survival is associated with surgical treatment.

Micro-recanalization in a biodegradable graft for reconstruction of the vas deferens is enhanced by sildenafil citrate.

This study investigated the effect of sildenafil citrate on micro-recanalization and neovascularization, which were previously demonstrated in a rat model using biodegradable grafts (BGs) for vas deferens reconstruction. A total of 24 male rats underwent bilateral vasectomy with removal of a 0.5-cm vasal segment and were randomly assigned to four groups. Groups 1 and 2 underwent immediate vasovasostomy. Groups 3 and 4 underwent interposition of a 0.5-cm BG in the vasal gap. Groups 1 and 3 were given 5 mg kg(-1) day(-1) oral sildenafil. Other groups were given placebo. Rats were housed with females 12 weeks postoperatively. Reconstructed vasal segments were harvested 16 weeks postoperatively and analyzed histologically. Fluid from the distal vasal stump was analyzed for motile sperm. Urine samples obtained 16 weeks postoperatively were analyzed for cGMP levels. cGMP levels in rats treated with sildenafil were significantly higher than in control rats. No pregnancies were sired by grafted groups. In all, 5/6 rats in group 1 and 3/6 rats in group 2 sired litters. No motile sperm were noted in the vasal fluid of the grafted groups. Motile sperm were noted in all rats in group 1 and in 5/6 rats in group 2. In addition, 29 and 4 microcanals were detected in the sildenafil and placebo groups, respectively (P = 0.023). No microcanal exceeded 3 mm in length. An average of 12 and 28 blood vessels per graft were noted in the placebo and sildenafil groups, respectively (P < 0.0001). In conclusion, sildenafil enhances micro-recanalization and neovascularization in BG used for vas deferens reconstruction, but does not increase the microcanal length after 16 weeks.

Antibody expiration in the context of resource limitation: what is the evidence basis?

The implementation and enforcement of the College of American Pathologists Survey Checklist ANP 22432 has renewed attention on the issue of outdating of antibodies used for immunohistochemical analysis. The current study examined the staining patterns of 26 recently acquired primary antibodies and their expired counterparts. Two reviewers examined sequential sections of formalin-fixed, paraffin-embedded tissue samples for staining intensity and percentage of positivity. Appropriate positive and negative control studies were performed. Of the 26 antibodies, 20 exhibited no difference in percentage of positivity or staining intensity. Of the remaining 6, 3 showed better performance with the expired cohort and 3 with nonexpired antibodies. However, no antibody staining characteristics varied by more than 1 step, and in no case was positive staining lost after antibody expiration. Negligible differences exist in immunostaining between outdated and current antibodies. Thus, exemption for primary antibodies from existing regulations would conserve resources without adversely impacting patient care.

Pathology education: quo vadis?

The teaching of pathology and the face of pathology as a career are changing rapidly. A short questionnaire was constructed covering key areas impacted by curricular change to collect data for a workshop to be held at the Annual Meeting of the West and Mid-West Region of the Association of Pathology Chairs. Questions included the ongoing existence of pathology as a separate discipline, the degree of 'control' exercised by pathology faculty, the length of the course (hours), the use of microscopes, and selected outcomes data, specifically National Board of Medical Examiners graphs of comparative performance of disciplines and US Medical Licensing Examination Step 1 data. The written responses and discussion by attendees at the meeting are presented with preliminary analysis and commentary. It was concluded that 'evidence-based education' represents something of a novelty, worthy of further study.

Her-2/neu expression in salivary duct carcinoma: an immunohistochemical and chromogenic in situ hybridization study.

Salivary duct carcinoma (SDC) shares significant morphologic and immunophenotypic overlap with ductal carcinoma of the breast, including HER-2/neu expression. Previous studies have detected HER-2/neu at the protein level in SDCs; however, no study, to date, has assayed whether this expression is related to gene amplification detected by chromogenic in situ hybridization (CISH). Formalin-fixed, paraffin-embedded tissue sections from 12 previously diagnosed SDCs were evaluated by immunohistochemistry (IHC) and CISH for HER-2/neu status. Result concordance was seen in all 12 cases. A total of 4 SDCs were positive by IHC; all 4 cases showed amplification with CISH. The remaining 8 cases were negative by IHC and showed no gene amplification with CISH. SDCs in this study show HER-2/neu overexpression on both the protein and gene levels in approximately 30% of cases. These findings suggest a role may exist for Herceptin (trastuzumab) based therapy in some SDC patients.

RDP58 inhibits T cell-mediated bladder inflammation in an autoimmune cystitis model.

Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder with a strong autoimmune component. Currently, the major challenge in IC treatment is the development of effective therapies. RDP58 is a novel d-amino acid decapeptide with potent immunosuppressive activity. In this study, we investigated whether RDP58 was effective as an intravesical agent for treating bladder autoimmune inflammation in a transgenic mouse model (URO-OVA mice). URO-OVA mice were adoptively transferred with syngeneic activated splenocytes of OT-I mice transgenic for the OVA-specific CD8(+) TCR for cystitis induction and treated intravesically with RDP58 at days 0 and 3. Compared with controls, the RDP58-treated bladders showed markedly reduced histopathology and expressions of mRNAs and proteins of TNF-alpha, NGF and substance P. To determine whether the inhibition of bladder inflammation by RDP58 was due to the interference with effector T cells, we treated the cells with RDP58 in vitro. Cells treated with RDP58 showed reduced production of TNF-alpha and IFN-gamma as well as apoptotic death. Collectively, these results indicate that RDP58 is effective for treating T cell-mediated experimental autoimmune cystitis and may serve as a useful intravesical agent for the treatment of autoimmune-associated bladder inflammation such as IC.

Emerging eosinophilic (allergic) esophagitis: increased incidence or increased recognition?

CONTEXT: Eosinophilic esophagitis is a disease of the esophagus with distinct histologic features (prominent intraepithelial eosinophils, particularly superficial with clustering) and characteristic endoscopic features (trachealization, white plaques). The presence of intraepithelial eosinophils had been recognized since 1982 as indicative of reflux esophagitis but little attention was initially paid to their numbers or location. Eosinophilic esophagitis has been recently described and there have been a number of reports that its incidence is on the rise. It had been our impression that eosinophilic esophagitis was being seen more frequently, perhaps resulting from some environmental change. OBJECTIVE: To investigate the increased prevalence of eosinophilic esophagitis. DESIGN: We analyzed a similar group of cases from 2005 (n = 150) as compared with 1990 (n = 115). Consecutive patients with mucosal esophageal biopsies from May through June of the respective years were included in the analysis. Patients with Barrett metaplasia or with carcinoma were excluded. The highest density of intraepithelial eosinophils for each patient was recorded as the number of intraepithelial eosinophils per single high-power field. The patients were categorized by the number of intraepithelial eosinophils per high-power field with those cases with greater than 20 intraepithelial eosinophils per high-power field representing eosinophilic esophagitis. RESULTS: There was no difference in the incidence of eosinophilic esophagitis between 1990 and 2005. CONCLUSIONS: The apparent increased incidence of eosinophilic esophagitis is largely a result of an increase in recognition rather than an increase in disease resulting from an environmental factor.

Comparison of fungal culture versus surgical pathology examination in the detection of Histoplasma in surgically excised pulmonary granulomas.

CONTEXT: Granulomatous pulmonary nodules are common in areas endemic for Histoplasma infection, and may require surgical excision to exclude neoplasia. Surgeons may elect to routinely send material directly to the clinical microbiology laboratory for fungal and mycobacterial cultures. OBJECTIVE: To determine if tissue from surgically excised pulmonary granulomatous nodules removed from patients in a geographic area endemic for Histoplasma infection should be routinely submitted for fungal culture. DESIGN: Retrospective review and comparison of surgical pathology histochemical findings and clinical microbiology results of 30 surgical (wedge) lung excisions that demonstrated granulomatous nodule at the time of frozen section. RESULTS: Twenty cases demonstrated fungal organisms consistent with Histoplasma species via histochemical fungal stains. Of these 20 cases, 17 were tested in the microbiology laboratory using direct smear examination and fungal culture; Histoplasma was detected in 1 case (1/17). Eight cases revealed no organisms by surgical pathology. Of these, 6 were tested in the microbiology laboratory, and all 6 were negative by culture and direct smear (0/6). The remaining 2 cases demonstrated organisms other than Histoplasma by surgical pathology examination. CONCLUSIONS: Surgical pathology examination of granulomatous pulmonary nodules detected Histoplasma organisms with greater sensitivity than culture and direct smear. There were no false-negative surgical pathology diagnoses when compared with microbiological results. These findings suggest that it is not necessary to routinely send material from solitary pulmonary granulomas for fungal culture when the material is removed from immunocompetent patients in a geographic area endemic for histoplasmosis.

Chondroblastoma of the femoral diaphysis: report of a rare phenomenon and review of literature.

Chondroblastoma (CB) is a relatively rare yet well-studied benign neoplasm of bone. The purported neoplastic cell is the chondroblast, a cell which normally populates areas of secondary ossification. Numerous studies have shown that CB overwhelmingly arises from the epimetaphyseal region of skeletally immature individuals. Only rare cases have been reported in the diaphyseal region, and many of these involve metacarpals or metatarsals, which may lack a true anatomic diaphysis. The remaining cases of diaphyseal CBs synchronously involve the neighboring epimetaphysis, making determination of the initiation point impossible. We report a case of a CB isolated to the radiologic femoral diaphysis. To our knowledge, this is the first case of a diaphyseal-based CB to be reported in the pathology literature and only the second case published overall.

Ethanol as a local adjuvant for giant cell tumor of bone.

Giant cell tumor is an aggressive benign neoplasm of bone. A number of adjuvant agents have been used to supplement intralesional curettage to reduce the otherwise high local recurrence rate. High concentration ethanol is more readily available and less toxic to use than some common alternatives. No report on its use in a group of patients with giant cell tumor is available. Records were retrospectively reviewed for all giant cell tumors treated by intralesional curettage and high concentration ethanol irrigation as the only chemical adjuvant. Twenty-five primary excisional curettages and 12 repeat curettages for giant cell tumors of bone were performed in 31 patients. Patients were followed for a mean of three years and 10 months. There were five recurrences after primary excision procedures, and three after repeat excisions. Only use of a high-speed burr and lower Campanacci staging correlated with reduced recurrence rate, and these were not statistically significant. Most defects were filled with allograft or calcium sulfate. In the 11 patients treated primarily with curettage using a high-speed burr and adjuvant ethanol with minimum two-year follow-up, only one stage 3 lesion in a distal radius recurred. Multiple washes with high concentration ethanol, when used in conjunction with aggressive curettage including high-speed burring, is an effective and safe adjuvant. The necessity of any chemical adjuvant after appropriately aggressive curettage and burring can only be definitively demonstrated with a prospective, randomized, multi-center trial. Until such evidence becomes available, the use of adjuvant ethanol offers a compromise between higher toxicity adjuvants and no chemical adjuvant at all.