From Dyspepsia to Diagnosis: A Rare Gastric Subepithelial Lesion Definitively Diagnosed via Endoscopic Submucosal Dissection and Immunohistochemistry.

INTRODUCTION: Peripheral nerve sheath tumors, known as perineuriomas, are typically found on the trunk and extremities. They are less commonly described in the gastrointestinal tract (GI), and extremely rarely are described in the stomach. CASE PRESENTATION: We present a case of a 2-cm gastric perineurioma in a 42-year-old patient with nonspecific GI complaints of chronic dyspepsia and epigastric discomfort. Esophagogastroduodenoscopy, followed by endoscopic ultrasound, revealed a 2-cm umbilicated lesion in the stomach, which was subsequently removed with endoscopic submucosal dissection and sent for pathology. Immunohistochemical staining revealed a rare entity known as a gastric perineurioma. CONCLUSION: Since the first case of gastric perineurioma was first described in 2004, there have only been 4 reported cases in the English literature. This case highlights the crucial interdisciplinary multidisciplinary effort between pathologists and GI specialists required to reach this diagnosis and showcases endoscopic diagnosis using endoscopic dissection, which allows for complete lesion resection and complete resolution of the patient's symptoms.

Early-stage Uterine Pure and Mixed Clear Cell Carcinoma: Outcomes and Recurrence With and Without Adjuvant Therapy.

OBJECTIVE: Clear cell carcinoma (CCC) of the uterus is a rare but aggressive histology for which the role of adjuvant therapy for stage I-II disease is unclear. Our study investigated outcomes and patterns of failure in these patients. METHODS: We found 64 cases of CCC, including 26 of pure CCC, 22 mixed with endometrioid adenocarcinoma, and 16 mixed with uterine papillary serous carcinoma. Adjuvant treatment was given to 55%. RESULTS: Median follow-up was 51.9 months. By Kaplan-Meier estimate, 5-year vaginal recurrence-free survival (RFS) was 91.3%, pelvic RFS was 92.6%, distant metastasis RFS was 81.6%, disease-free survival was 79.6%, and overall survival was 79.7%. Median time to recurrence was 20.7 months (range, 2 to 40.5 mo). Patients treated adjuvantly had higher proportion of stage II disease (40% vs. 6.9% observed, P=0.0031) and 20% (7/35) recurred. There were no significant differences in outcomes by histologic subtypes but numerically more recurrences with uterine papillary serous involvement. By univariate analysis, higher stage, presence of lymphovascular invasion, and lack of lymph node dissection were predictive of worse overall survival. Age 65 years and above was predictive of worse cancer-specific survival. Of 12 who progressed, only 1 was salvaged and 11 died of disease. Of progressors, 10 had documented distant metastasis. Median time from recurrence to death was 4.5 months (range, 0.2 to 21.2 mo). CONCLUSIONS: Given aggressive and often unsalvageable nature of recurrence, consideration of adjuvant treatment (including chemotherapy and radiation) is warranted for early-stage CCC, particularly for stage II or those with poor prognostic factors.

Surgical Management of Chronic Pancreatitis.

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

Early stage papillary serous or clear cell carcinoma confined to or involving an endometrial polyp: outcomes with and without adjuvant therapy.

OBJECTIVE: To investigate clinical outcomes of stage IA uterine papillary serous (UPSC) and clear cell carcinoma (CC) arising from or associated with a polyp. METHODS: From 1995 to 2011, we identified 51 cases of stage IA UPSC (67%), CC (8%) or mixed histology (26%) endometrial cancer. Of these, 32 had disease confined to polyp (seven with no residual disease after hysterectomy), 14 had surface spread, 1 had myometrial invasion (MMI) and 4 had both. The majority of patients did not receive adjuvant therapy (80%). Patients given adjuvant treatment (either platinum-based chemotherapy alone, radiation alone, or a combination of the two) had incomplete staging or abnormal cytology. RESULTS: At mean follow-up of 58.3 months, only 4 patients had progressed, via pelvic adenopathy, carcinomatosis or both. There were no vaginal cuff recurrences. Kaplan-Meier 5 year estimates were pelvic control of 92.1%, disease-free survival 93% and OS 80.6%. Only 9% (3/32) of cases confined to polyp progressed. One responded to salvage chemoradiation, but two died despite salvage. Only 5% (1/19) of cases with surface and MMI progressed. On univariate analysis, only MMI and abnormal/positive cytology were significantly associated with increased pelvic recurrence (MMI p=0.0059, cytology p=0.0036) and worse DFS (MMI p=0.0018, cytology p=0.0054). Two patients given adjuvant treatment developed new gynecologic malignancies. CONCLUSION: In our study, patients with limited UPSC/CC disease involving a polyp who have complete workup did well without adjuvant therapy, with recurrence rates similar to UPSC/CC stage IA disease. Late and extensive pelvic relapses may occur in the few who do relapse.

Rosette-forming glioneuronal tumor: a pineal region case with IDH1 and IDH2 mutation analyses and literature review of 43 cases.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a mixed glio-neuronal neoplasm recently codified by the World Health Organization WHO Classification of Central Nervous System (CNS) Tumors (2007). To date, 43 cases have been described in the literature; most occurring in the fourth ventricle region. We report the fourth case involving the pineal region in a 16-year-old female with signs of increased intracranial pressure (ICP). A stereotactic biopsy of the mass was followed by a debulking procedure. Both specimens revealed classic RGNT histology. The patient had stable scans 7 months post-resection. The clinical, radiological and histopathologic features of the previously described 43 cases are reviewed along with our illustrative case. Mean age of patients was 30 ± 12.8 years with 1.9:1 female to male ratio. The most common presenting signs related to increased ICP and posterior fossa involvement, including: headache (62.8%), ataxia (39.5%) and vomiting and vertigo (both 16.3%). This tumor usually presents with cystic changes (54.5%) with focal enhancement (60.9%) and hydrocephalus (43.2%). Microcalcifications and satellite lesions were common radiographic observations. All reported cases had the classic biphasic pattern. Rosenthal fibers and eosinophilic granular bodies are each present in approximately two thirds of cases. Ki-67 labeling index is consistently low (mean (%): 1.8 ± 0.75 SD). The isocitrate dehydrogenase 1 or 2 mutation found in low grade diffuse gliomas is not identified in this RGNT case. Reported outcome is nearly uniformly excellent after complete or subtotal resection. A solitary report of recurrence after 10 years and the limited experience with this entity suggest that long term follow up is advisable.

Close or positive margins after mastectomy for DCIS: pattern of relapse and potential indications for radiotherapy.

PURPOSE: Mastectomies result in very high local control rates for pure ductal carcinoma in situ; however, close or involved tumor margins are occasionally encountered. Data regarding the patterns of relapse in this setting are limited. METHODS AND MATERIALS: Between 1994 and 2002, the pathology reports of 574 patients who had undergone mastectomy at our institution for pure ductal carcinoma in situ were retrospectively reviewed. Of the 574 patients, 84 were found to have margins of <10 mm. Of the 84 patients, 4 underwent postoperative radiotherapy and were excluded, leaving 80 patients for this analysis. Of the 80 patients, 31 had margins <2 mm and 49 had margins of 2.1-10 mm. High-grade disease was observed in 47 patients; 45 patients had comedonecrosis; and 30 had multifocal disease. Of the 80 patients, 51 were <60 years of age. RESULTS: With a median follow-up of 61 months, 6 (7.5%) of the 80 patients developed local recurrence. Of the 31 patients with a margin of

Collision tumor of thyroid: metastatic lung adenocarcinoma plus papillary thyroid carcinoma.

Collision tumors are rare entities wherein 2 separate, distinct histologic malignant neoplasms occur in adjacent anatomic proximity. The 2 malignancies may originate from the same organ or occur as metastases from other sites. We present a case of a collision tumor of metastatic lung adenocarcinoma and papillary thyroid carcinoma occurring in the thyroid gland of a 63-year-old woman who presented with a multinodular central neck mass. After excision and histopathologic examination, this tumor was identified as a collision tumor. This is the first report of this unique combination of tumors occurring in the thyroid gland. This case report emphasizes the role of detailed histopathologic analysis and the use of immunohistochemistry in better identifying rare thyroid neoplasms.

Expression of epithelial membrane protein-2 is associated with endometrial adenocarcinoma of unfavorable outcome.

BACKGROUND: Epithelial membrane protein 2 (EMP2) is an estrus-regulated tetraspan protein that is required for endometrial competence in blastocyst implantation. EMP2 controls surface levels of several classes of integrin and other cell-interaction molecules, and their trafficking to glycolipid-enriched lipid raft domains is important in receptor signaling. These features suggest that EMP2 may contribute to neoplastic traits of endometrial cancer. The objective of this study was to determine the prevalence of EMP2 expression in endometrial neoplasms and its clinical significance. METHODS: EMP2 immunophenotype, histologic diagnosis, grade, the presence of lymphovascular invasion, disease stage, and clinical follow-up were determined for 99 endometrial cancers. RESULTS: Significant EMP2 expression (EMP2 positive) was observed in 12 of 99 cancers (9 endometrioid [6 International Federation of Gynecology and Obstetrics Grade 3], 1 serous, 1 mixed endometrioid and serous, and 1 mixed endometrioid and clear cell), and weak EMP2 expression was observed in 11 cancers. EMP2-positive tumors were more likely than others to be myometrium invasive, high stage, and recurrent, persistent, or fatal. The overall median survival for patients with EMP2-positive tumor was only 23 months, whereas the medial survival was not reached for patients with EMP2-weak and EMP2-negative tumors. The median disease-free interval was only 11 months for patients with EMP2-positive tumors and was not reached for patients with EMP2-weak and EMP2-negative tumors. A multivariate analysis of disease-free survival demonstrated independent, negative prognostic significance for EMP2 expression, high stage, and high-risk histologic subtypes. CONCLUSIONS: EMP2 expression is a feature of some prognostically unfavorable endometrial cancers. Its utility for clinical decision making and its biologic role in endometrial cancer deserves further study in a larger series of patients.

Ectopic decidua of pelvic lymph nodes: a potential diagnostic pitfall.

Ectopic decidua is one of several benign lymph node inclusions that have been increasingly documented in the literature, most often in postmortem examinations of pregnant woman and recently in pregnant women with cervical squamous cell carcinoma. Although lacking clinical significance of its own, the major diagnostic implication would be misdiagnosis as metastatic carcinoma in the lymph node. Intraoperative frozen sections are often performed prior to radical hysterectomy, leading to a potential alteration of therapy if metastatic carcinoma is identified in the lymph nodes. We report such a case of a pregnant woman with cervical squamous cell carcinoma requiring lymphadenectomy and hysterectomy, in which the intraoperative frozen section of a pelvic lymph node with ectopic decidual change was mistakenly identified as metastatic carcinoma. Its histologic resemblance to carcinoma and location within subcapsular sinuses, compounded with the fact that ectopic lymph node decidua is not commonly seen in routine practice, can lead to this diagnostic pitfall. We review the literature regarding ectopic decidua, its presence in lymph nodes, and its pathogenesis, as well as review the literature on benign lymph node inclusions.

Fine-needle aspiration of an adenoid cystic carcinoma of the larynx mimicking a thyroid mass.

Adenoid cystic carcinoma (ACC) is most often primary in the major and minor salivary glands but can also arise from the submucosal seromucinous glands of the larynx and trachea. We report a case of adenoid cystic carcinoma of the larynx that presented as a diffuse swelling in the thyroid area. Fine-needle aspiration (FNA) was consistent with a neoplastic process, which was difficult to classify further but was felt to be of thyroid origin. Subsequent gross and histopathologic examination showed the lesion to represent an ACC arising from the larynx. This case highlights the need to be aware of unusual lesions that may arise in the region of the thyroid. Knowledge of these non-thyroidal lesions that can clinically mimic a thyroid mass will help in making the correct cytologic diagnosis when these lesions are sampled by FNA.

Lymphovascular and perineural invasion in the parametria: a prognostic factor for early-stage cervical cancer.

OBJECTIVE: To estimate the impact of parametrial lymphovascular and perineural involvement on nodal metastasis and failure pattern of women with early-stage, surgically treated cervical cancer. METHODS: Clinical records and pathologic slides of 93 patients with early-stage cervical cancer (2 IA2, 52 IB1, 31 IB2, and 8 IIA) treated with radical hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy were reviewed. The study group comprised 80 patients with squamous cell carcinoma and 13 patients with adenocarcinoma of the cervix. Median follow-up time was 33 months. The association among the various histopathologic predictors of outcome was determined with chi2 analysis. The influence of the predictors on outcome was examined with log rank survival methods and the Cox regression model. RESULTS: The presence of parametrial lymphovascular space invasion is a predictor of disease in the pelvic (P<.001) and paraaortic (P<.05) lymphatics independently. Large tumor size (greater than 4 cm), parametrial perineural invasion, cervical lymphovascular space invasion, and tumor depth (greater than two thirds) were found to be simultaneous predictors of recurrence on multivariate analysis (P<.05). Using these four binary predictor variables, we have computed a model-based relative risk. Based on this model, the presence of perineural invasion in the parametria more than doubles the risk of recurrence in the cohort of patients with large (greater than 4 cm) tumors (P<.05). In a subset analysis of patients with negative nodal disease, parametrial perineural invasion and tumor size were independent predictors of poor outcome (P<.05). CONCLUSION: Presence of parametrial lymphovascular space invasion correlates significantly with the risk of nodal metastasis in women with early-stage cervical cancer. Parametrial perineural invasion is an independent poor prognostic factor. Histopathologic findings within the parametria are a valuable independent predictor of recurrence and thus may influence the selection of patients for adjuvant treatment.

Simultaneous occurrence of medullary and papillary carcinoma of the thyroid gland identified by fine needle aspiration. A case report.

BACKGROUND: Fine needle aspiration (FNA) diagnosis of simultaneous medullary and papillary thyroid carcinoma in independent thyroid lobes is exceedingly rare. CASE: A 36-year-old female presented with a one-month history of dysphagia. Thyroid ultrasound revealed a multinodular goiter. She was clinically and biochemically euthyroid. FNA of the right thyroid nodule was consistent with medullary carcinoma, and FNA of the left thyroid lobe was consistent with papillary carcinoma. Immunohistochemistry revealed strong calcitonin and CEA positivity in the right lobe and lack of staining in the left lobe. Conversely, staining for thyroglobulin was negative on the right lobe and positive on the left lobe. CONCLUSION: The patient developed tumors in separate lobes of the thyroid. Immunoreactivity of calcitonin, CEA and thyroglobulin made a sharp distinction between the two tumors. Therefore, we conclude that these tumors were not linked by either embryology or genetics.

Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father.

In humans, mutations in the testis-determining gene SRY result in XY sex reversal with pure gonadal dysgenesis (PGD). However, only about 10-15% of the cases of PGD can be explained by mutations within the SRY open reading frame, suggesting the existence of other sex-determining genes. Although SRY is known to bind and bend DNA, its target and mode of action remain elusive. Here, we describe a novel mutation in SRY at codon 127, resulting in a tyrosine (Y) to phenylalanine (F) substitution in the protein. This sequence variant was found not only in the XY female patient but also in her father, who is a phenotypically normal male. However, this Y127F variant was not found in the SRY sequences of 93 other randomly chosen males. This substitution affects a highly conserved tyrosine residue in the HMG box of SRY, in which two de novo mutations have been described previously in XY females with PGD. Furthermore, electromobility shift studies demonstrate that SRY protein harboring the Y127F variant is incapable of binding consensus SRY binding sites in vitro. Taken together, these data suggest that the Y127F variant is a novel mutation with functional consequences and not simply a polymorphism. The allelic variant of SRY transmitted in this family and shared by both a phenotypic female (proband) and a phenotypic male (proband's father) emphasizes the importance of modifier genes in the sex determination pathway.

Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer.

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. However, reliable diagnostic or prognostic tumor markers have not been identified for endometrial cancer. In this study, we examined whether urokinase plasminogen activator receptor (UPAR), a glycosyl-phosphatidylinositol-linked membrane protein, is a candidate diagnostic or prognostic marker for patients with cancer of the endometrium. Sixty-five surgically excised, formalin-fixed endometrial tissue specimens were accessioned through the Department of Pathology Registry at the University of California, Los Angeles, and analyzed for UPAR expression by using immunohistochemical techniques. A retrospective review was also performed to determine stage and histopathologic grade of disease, recurrence, and mortality. No expression of UPAR protein was present in seven patients with benign neoplasia of the endometrium. UPAR protein expression highly correlated with stage of disease (ungrouped Spearman correlation = 0.625, P < 0.0001): 40% of patients with stage I, 66% of patients with stage II, 100% of patients with stage III, and 85% with stage IV demonstrated the highest level of UPAR expression. Moreover, high UPAR expression positively correlated with grade of disease (ungrouped Spearman correlation = 0.71, P < 0.0001): 29% of grade 1 specimens, 57% of grade 2, and over 90% of specimens with grade 3, the majority representing uterine papillary serous carcinoma and mixed malignant mesodermal tumor. Finally, UPAR protein expression also positively correlated with rate of recurrence and mortality in patients with adenocarcinoma of the endometrium (ungrouped P = 0.034). Our data suggest that UPAR is a useful prognostic marker for biologically aggressive forms of endometrial cancer.