Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria.

Previously, our international team proposed a three-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification-A tumors have well-demarcated glands lacking destructive stromal invasion or lymphovascular invasion, Pattern Classification-B tumors show localized, limited destructive invasion arising from A-type glands, and Pattern Classification-C tumors have diffuse destructive stromal invasion, significant (filling a 4 × field) confluence, or solid architecture. Twenty-four cases of Pattern Classification-A, 22 Pattern Classification-B, and 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis originally established. One H&E slide per case was reviewed by seven gynecologic pathologists, four from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near-complete (six of seven) agreement in 50%. Overall concordance was 74%. Overall kappa (agreement among pathologists) was 0.488 (moderate agreement). Pattern Classification-B has lowest kappa, and agreement was not improved by combining B+C. Six of seven reviewers had substantial agreement by weighted kappas (>0.6), with one reviewer accounting for the majority of cases under or overcalled by two tiers. Confluence filling a 4 × field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis-B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can be reproducibly applied by gynecologic pathologists. Further refinement of criteria should allow use of this powerful classification system to delineate which cervical adenocarcinomas can be safely treated conservatively.

Is there a role for anterior zone sampling as part of saturation trans-rectal ultrasound guided prostate biopsy?

BACKGROUND: The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx. METHODS: 127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies. RESULTS: Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%). CONCLUSIONS: TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.

Do deeper sections increase the frequency of detection of serous tubal intraepithelial carcinoma (STIC) in the "sectioning and extensively examining the FIMbriated end" (SEE-FIM) protocol?

Studies have suggested serous tubal intraepithelial carcinoma (STIC) of the fallopian tube to be a putative precursor to ovarian and peritoneal serous carcinoma. It has been recommended that resected fallopian tube specimens should be rigorously examined for STIC, especially in women at high risk of serous carcinoma, such as those with BRCA mutations or with a strong family history. The SEE-FIM protocol allows for the greatest surface area of the tube to be histologically assessed. There have been suggestions that multiple deeper sections should be examined if the initial hematoxylin and eosin (H&E) sections are negative; however, whether this identifies more cases of STIC has not rigorously examined. We examined deeper sections from 56 cases of pelvic carcinoma in which the initial H&E sections of the fallopian tubes were negative for STIC. All initial and deeper sections underwent consensus review by panel of experts in gynecologic pathology. These cases are part of a larger study in which we had examined 300 consecutive bilateral salpingectomies using the SEE-FIM protocol and a single-H&E section per block and had identified 68 cases of pelvic serous carcinoma, of which 12 were associated with STIC. We calculated the sensitivity of a single-H&E section to detect STIC, as compared with examination of multiple deeper sections, and reevaluated the clinicopathologic data of the parent study in light of the additional cases of STIC. In the 56 cases initially negative for STIC, 4 cases of STIC were identified after examination of multiple deeper sections of the fallopian tubes. The single-H&E section SEE-FIM approach therefore detected only 75% (95% confidence interval, 51%-90%) of STIC that was present. Three of these new cases were associated with primary ovarian serous carcinoma and 1 with primary peritoneal serous carcinoma. All 3 new cases associated with ovarian carcinoma were noted in women without neoadjuvant chemotherapy. In considering the data from the parent study, we calculated a statistically significant lower incidence of STIC in women with ovarian serous carcinoma who received neoadjuvant chemotherapy as compared with those who did not (P=0.042). Our study demonstrated that additional cases of STIC can be detected if deeper sections are examined. These additional cases also highlighted a statistically significant difference in the incidence of STIC associated with ovarian serous carcinoma who received neoadjuvant chemotherapy relative to those who did not. Consideration to this should be given in future studies of the prevalence of STIC and to routine examination of salpingectomy specimens from women at high risk for pelvic serous carcinoma.

Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

Frequency of serous tubal intraepithelial carcinoma in various gynecologic malignancies: a study of 300 consecutive cases.

Serous tubal intraepithelial carcinoma (STIC) has been implicated in the pathogenesis of pelvic serous carcinoma. We hypothesized that, if this is the case, the frequency of STIC should be substantially lower in endometrial serous carcinomas, in nonserous gynecologic malignancies, and in benign gynecologic neoplasms than in ovarian or peritoneal serous carcinomas. From 2007 to 2009 the fallopian tubes of 342 consecutive gynecologic cases were entirely submitted for histology using the Sectioning and Extensively Examining the FIMbriated end protocol. This study included 300 of these cases (277 TAH-BSO, 23 BSO) after exclusion. The hematoxylin and eosin-stained slides from the fallopian tubes were independently reviewed by 2 gynecologic pathologists who were blinded to all other findings; disagreements were resolved by a third pathologist. Among 46 cases of ovarian malignancies, STIC was identified in 6 (18.8%) of 32 cases of serous carcinoma, but not in any other subtype. Similarly, STIC coexisted in 4 (14.3%) of 28 cases of endometrial serous carcinoma; however, no STIC was identified in any of the 74 cases of nonserous endometrial malignancies. STIC was identified in 2 (28.6%) of 7 cases of peritoneal serous carcinoma. No STIC was identified among 15 nongynecologic malignancies, 90 cases of benign conditions, and 27 cases of other conditions including 4 cases of cervical adenocarcinoma in situ and high-grade cervical intraepithelial lesions, 8 cases of endometrial atypical complex hyperplasias, and 15 cases of ovarian borderline tumors. In conclusion, the fallopian tube may be the origin of some pelvic serous carcinomas. Other possibilities that may explain the origin of pelvic high-grade serous carcinoma are discussed. Given that STIC coexisted with 14% of endometrial serous carcinomas, a more unifying theory may be that gynecologic serous carcinomas and STIC are multifocal lesions.

Construction of tissue micro array from prostate needle biopsies using the vertical clustering re-arrangement technique.

BACKGROUND: Tissue microarray (TMA) allows for simultaneous rapid expression analysis of multiple molecular targets in many tissue specimens. TMA's are specifically in demand for the screening for diagnostic and prognostic markers in prostate cancer (PC). Consequently, TMAs from prostate needle biopsy (PNB) material taken at diagnosis before any treatment commenced are in demand. However, since PNB contain only limited amount of tumor arranged within a very thin tissue core, TMA construction from PNB is problematic. METHODS: Archival PNB from 30 PC patients with variable Gleason scores (6-10) and % of cores involvement (30-90%) were used. Following selection of representative cores, the paraffin blocks were melted. Each core was sectioned into equal parts of 3-4 mm in length. For each case, a group of fragments was then re-embedded in a vertical orientation. Using Manual TMA Apparatus, 2 mm cores from each of the vertically rearranged fragments were harvested. Sections (4 µm) were stained with H&E and with high-molecular weight cytokeratin (HMWCK), PIN-cocktail (p63 + p504S), and PSA immunohistochemical stains. RESULTS: A TMA from PNB with a capacity of 80 serial 4 µm sections was constructed. In all cases, identical tumor and neighboring tissue morphology (atrophic changes and high-grade prostatic intra-epithelial neoplasia) with no loss of tissue was evident. CONCLUSIONS: The vertical clustering re-arrangement (VCR) technique is suitable for large scale construction of TMA blocks from PNB maintaining the morphological and immunohistochemical characteristics of the original samples. This method is promising both in terms of archival tissue preservation and biomarkers research.

Malignant giant cell tumor of the vulva.

Giant cell malignant fibrous histiocytoma or giant cell tumor of the soft parts (GCTSP) is a rare soft tissue tumor. GCTSP has an unpredictable behavior; the majority of the reported cases showed benign histology and those that showed malignant morphologic features were extremely rare. To the best of our knowledge, GCTSP has never been reported to involve the vulva in the English literature. We report the first case of malignant GCTSP of the vulva. Histologic features and the immunoprofile of the tumor and differential diagnosis are discussed in detail. Although extremely rare, consideration of the potential occurrence of GCTSP in the vulva is recommended to avoid a potential diagnostic pitfall.

Clear cell hidradenoma: an unusual vulvar tumor.

Clear cell hidradenoma (CCH) is a benign skin appendageal tumor. Most cases occur in the skin of the head and face. The tumor usually presents as a solitary firm dermal nodule. Histologically, it is a well-circumscribed, nonencapsulated tumor formed of 2 cell types, one with clear cytoplasm and the other with dark eosinophilic cytoplasm. Although most cases are benign, occasional cases with malignant transformation have been reported. We report a case of CCH in a very unusual location. To the best of our knowledge, CCH has not been previously described in this site, in the English literature. Although rare, inclusion of CCH should be included in the differential diagnosis of benign solid and clear cell tumors of the vulvar skin.

Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.

Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate.

PURPOSE: To determine if iridium implant (IM) and external-beam radiation therapy (EBRT) is better than standard EBRT in locally advanced prostate cancer. METHODS: Patients with T2 and T3 prostate cancer with no evidence of metastatic disease were randomly assigned to EBRT of 66 Gy in 33 fractions during 6.5 weeks or to IM of 35 Gy delivered to the prostate during 48 hours plus EBRT of 40 Gy in 20 fractions during 4 weeks. The primary outcome consisted of biochemical or clinical failure (BCF). BCF was defined by biochemical failure, clinical failure, or death as a result of prostate cancer. Secondary outcomes included 2-year postradiation biopsy positivity, toxicity, and survival. RESULTS: Between 1992 and 1997, 51 patients were randomly assigned to receive IM plus EBRT, and 53 patients were randomly assigned to receive EBRT alone. The median follow-up was 8.2 years. In the IM plus EBRT arm, 17 patients (29%) experienced BCF compared with 33 patients (61%) in the EBRT arm (hazard ratio, 0.42; P = .0024). Eighty-seven patients (84%) had a postradiation biopsy; 10 (24%) of 42 in the IM plus EBRT arm had biopsy positivity compared with 23 (51%) of 45 in the EBRT arm (odds ratio, 0.30; P = .015). Overall survival was 94% in the IM plus EBRT arm versus 92% in the EBRT arm. CONCLUSION: The combination of IM plus EBRT was superior to EBRT alone for BCF and postradiation biopsy. This trial provides evidence that higher doses of radiation delivered in a shorter duration result in better local as well as biochemical control in locally advanced prostrate cancer.

Microinvasive cervical adenocarcinoma (FIGO stage 1A tumors): results of surgical staging and outcome analysis.

Although studies suggest that microinvasive cervical adenocarcinoma has an excellent prognosis, none has reported treatment-related complications and many have lacked detailed measurement criteria. Our study looks at the rate of lymph node metastases and outcome, including complications, in patients with FIGO 1A1 and 1A2 adenocarcinomas of the cervix. Invasion was strictly defined, and the method of measurement was standardized. Villoglandular, papillary serous and clear cell carcinomas were excluded, as were tumors in which invasion exceeded 7 mm in width or 5 mm in thickness, with tumor thickness measured from the basement membrane of the overlying endocervical or ectocervical surface to the deepest focus of invasive tumor. A mean follow-up of 54 months (range, 5-159 months) was available for 31 of 32 (97%) patients. A total of 29 of 32 patients underwent hysterectomies, 2 patients had radical trachelectomies, and 1 patient was treated by cone biopsy. One patient received adjuvant radiotherapy. A total of 27 of 32 patients had bilateral pelvic lymph node dissections, and no lymph node metastases were identified. No recurrences have been reported to date. One patient died of metastatic ovarian carcinoma 82 months after her diagnosis of cervical carcinoma. Two of 27 (7%) patients have chronic leg edema secondary to lymph node dissection. Given the excellent prognosis of this tumor, the absence of lymph node metastases and a lymph node dissection complication rate of 7%, less radical surgery should be considered in this low-risk patient population.

Microsatellite Genotyping to Distinguish Somatic ß-HCG Secreting Carcinoma from Epithelioid Trophoblastic Tumor.

Objective. Morphologically, ß-HCG secreting somatic carcinoma can be difficult to distinguish from epithelioid trophoblastic tumors (ETT). However, their distinction is critical due to their potentially differing prognoses and choice of chemotherapy. Presence of biparental alleles in ETT can be identified with molecular testing. We describe a patient who presented with metastatic carcinoma and elevated serum ß-HCG and contrast this to an ETT in another patient. Data and Results. A 32-year-old female with recent possible miscarriage presented with pulmonary emboli and was found to have an increased serum ß-HCG, a retroduodenal mass, and multiple nodules in her lungs, liver, and para-aortic lymph nodes. Biopsy showed a ß-HCG and p63 positive epithelioid neoplasm with otherwise noncontributory immunohistochemistry. Molecular testing for biparental alleles in repeated length polymorphisms was negative, consistent with somatic origin. The second patient was a 35-year-old pregnant female with increased serum ß-HCG and a uterine epithelioid tumor positive for ß-HCG. Clinical and pathologic findings were characteristic of ETT and molecular testing was not required. These 2 cases illustrate that ß-HCG secreting tumors of different etiologies may have similar appearances, and when clinical and/or IHC findings are inconclusive, molecular testing may be useful.

Synchronous transitional cell carcinoma and metastatic hepatocellular carcinoma in the urinary bladder: a case report.

An 83- year-old male presented with intermittent hematuria and obstructive symptoms. A CT scan of the abdomen and pelvis showed diffuse thickening of the urinary bladder and a large 10 cm liver mass. Histopathological examination of bladder biopsy demonstrated two distinct lesions. The surface showed non-invasive urothelial carcinoma and the submucosa demonstrated metastatic hepatocellular carcinoma showing bile pigment and expressed Hep Par 1 and CD10. To the best of our knowledge, this is the first case report of synchronous transitional cell carcinoma and metastatic hepatocellular carcinoma of the urinary bladder.

Thromboembolic events in patients with urothelial carcinoma undergoing neoadjuvant chemotherapy and radical cystectomy.

OBJECTIVES: Patients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of this study was to assess the effect of cisplatin-based neoadjuvant chemotherapy (NCT) on the incidence of perioperative TEEs in patients undergoing radical cystectomy. METHODS AND MATERIALS: We analyzed a consecutive sample of 202 patients with urothelial carcinoma treated with radical cystectomy between 2005 and 2013. Data were collected retrospectively by reviewing medical records. Median follow-up was 16.9 months. Events of interest were defined as venous or arterial TEEs occurring from the date of diagnosis to 30 days after surgery. TEE incidence among patients treated with NCT and cystectomy was compared with that among patients treated with cystectomy alone using Fisher exact test and Cox proportional hazards regression. Proportional hazards regression was also used to assess whether TEE is a predictor of cancer progression and survival. RESULTS: Of 202 patients, 17 (8.4%) developed a TEE, including 8 of 42 (19.1%) treated with NCT and cystectomy and 9 of 160 (5.6%) treated with cystectomy alone (risk ratio = 3.39, 95% CI: 1.39-8.24). After adjustment for observation time, there remained an association between treatment with NCT and risk of TEE (hazard ratio = 2.40; 95% CI: 0.92-6.27; P = 0.07). Overall, 7 events occurred before cystectomy and 10 occurred postoperatively. Among patients treated with NCT, 6 of 8 events occurred before cystectomy. Detection of TEE was clinically significant as preoperative TEE was found to be an independent predictor of progression and cancer-specific mortality (adjusted hazard ratio = 3.91, 95% CI: 1.34-11.45). The main limitations of our study are its retrospective data collection and small absolute number of events. CONCLUSIONS: TEE occurs commonly in patients with urothelial carcinoma undergoing NCT. Preoperative TEE is an independent predictor of progression and cancer-specific mortality.

Underactivation of the adiponectin-adiponectin receptor 1 axis in clear cell renal cell carcinoma: implications for progression.

Energy-sensing pathways, normally coordinated by 5' AMP-activated protein kinase (AMPK), are dysregulated in renal cell carcinoma (RCC). Obesity can accentuate the pre-existing pro-tumorigenic metabolic machinery in RCC cells through its associated obesogenic hormonal milieu, characterized by lower circulating levels of adiponectin. In RCC patients, low adiponectin levels associate clinically with more aggressive disease. We investigated the adiponectin signaling pathway in RCC, focusing on adiponectin receptor 1 (AdipoR1) and associated activation of AMPK. AdipoR1 protein in RCC and normal surrounding renal tissues was determined by Western blot analysis and immunohistochemistry. Anti-tumorigenic effects of adiponectin in RCC cells in vitro were investigated via VEGF and MMP ELISA and invasion assays. Using in vivo models of RCC, the effect of AdipoR1-knockdown (shRNA) on tumor latency, growth and dissemination were determined. AdipoR1 protein was significantly reduced in clear cell RCC specimens. Adiponectin treatment inhibited VEGF, MMP-2 and MMP-9 secretion and activity and invasive and migratory capacities of RCC cells. AMPKα1-knockdown (shRNA) attenuated adiponectin's effects. In cells stably expressing AdipoR1-specific shRNA, AMPK activation by adiponectin was significantly reduced compared to cells expressing control shRNA. In vivo, AdipoR1 knockdown increased the growth, dissemination and angiogenesis of RCC. These findings suggest that deficiencies in the entire adiponectin hormonal axis (the hormone and its receptor) result in underactivation of AMPK leading to increased angiogenic and invasive capacities of RCC. The established link between obesity and RCC can therefore be further explained by the adiponectin deficiency in obese individuals together with reduced AdipoR1 protein in RCC.

Apocrine adenocarcinoma of the vulva.

Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget's disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from the native apocrine sweat glands or from anogenital mammary-like glands is still debatable. We report herein a case of a 67 year old female with a rare primary apocrine carcinoma of the vulva.

Interobserver agreement for assessing invasion in stage 1A vulvar squamous cell carcinoma.

Invasive squamous cell carcinoma of the vulva with ≤1 mm stromal invasion is classified as stage 1A. Cancer staging systems state that the depth of invasion should be measured from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of the invasive tumor. Measurement of the depth of invasion guides patient management. Even though this measurement is critical, no studies have reported the reliability among pathologists for determining the cutoff point of ≤1 mm stromal invasion in vulvar cancer. We assessed agreement among pathologists for determining whether a vulvar tumor is invasive, for the depth of invasion, and for tumor thickness. Forty-five cases of vulvar squamous cell carcinoma with a depth of invasion of ≤5 mm were chosen. Eleven gynecologic pathologists independently reviewed the slides and, for a subset of cases, pictorially recorded measurements on photographs. The number of cases that were reported as invasive by the 11 pathologists ranged from 21 to 44. The number of cases that were reported as showing a depth of invasion of ≤1 mm ranged from 7 to 27. Eight pathologists provided measurements for all lesions reported as invasive, the remaining 3 pathologists stated that they were unable to measure 2, 7, and 16 lesions, respectively. Mean κ for diagnosing vulvar carcinoma as invasive was 0.24 and for measuring the depth of invasion and thickness was 0.51 and 0.49, respectively. There was only fair agreement in determining whether the lesion was invasive. In cases in which pathologists agreed upon the diagnosis of invasion, agreement on depth was moderate. When using the recommended cancer staging method, interpretation of the location of the most superficial dermal papilla varied among pathologists. Measuring thickness did not improve agreement. This is the first study that has assessed the reliability of the diagnosis of invasion in vulvar cancer among gynecologic pathologists, the interobserver agreement for reporting the critical 1 mm threshold of depth of stromal invasion, and the way in which the International Federation of Gynecology and Obstetrics method is used by pathologists.

Buried penis: An unrecognized risk factor in the development of invasive penile cancer.

One of the documented benefits of neonatal circumcision is protection against invasive penile cancer. To date there have been a handful of published cases of invasive penile cancer in men circumcised as neonates. We report a case of a 73-year-old man, with a history of neonatal circumcision with no evidence of previous human papillomavirus exposure, who developed a buried penis secondary to obesity. He was diagnosed with Grade 2, pT3N0 squamous cell carcinoma of the penis. This report suggests that buried penis may pose a risk factor for the development of penile cancer despite the protective effects of neonatal circumcision. Thus periodic examination of a buried penis is warranted even in patients with no risk factors for penile cancer. A review of the literature is provided.