Mild Cytologic Atypia Research Articles

Epithelial Maturation Pattern of Dysplastic Epithelium and Normal Oral Epithelium Exposed to Tobacco and Alcohol: A Scanning Electron Microscopic Study

Background: The detection of oral cancer at an early stage is an optimal strategy and is the most effective approach for preventing further progression. The rationale of the study was to evaluate the epithelial maturation pattern in oral mucosa exposed to tobacco/alcohol and on dysplastic oral mucosa using the scanning electron microscope.Methods: Fifteen subjects were selected based on clinical examination and divided into three groups: group 1—patients with apparently normal oral mucosa; group 2—patients with oral mucosa exposed to tobacco/alcohol; group 3—patients with clinical diagnosis of leukoplakia. An incisional biopsy was performed from the buccal mucosa. One part of the specimen was prepared for light microscopy and the other part was prepared for scanning electron microscopy.Results: Light microscopy revealed nonkeratinized stratified squamous epithelium in group 1, while group 2 demonstrated hyperparakeratinized stratified squamous epithelium with mild cytological atypia, and group 3 showed architectural and cytological changes. Scanning electron microscopy demonstrated flat-surfaced cells with equidistant parallel microridges in group 1, while group 2 showed irregular and widened microridges with numerous pits and absence of honeycomb pattern. Group 3 showed irregularly arranged broad and swollen cells with numerous pits and irregular microvilli projecting over the surface.Conclusion: The present study establishes the relationship of the surface abnormalities to the tendency of the cells to become malignant and thus serves as a tool in early detection of squamous cell carcinoma. It also emphasizes the need of routine follow-up in these high-risk patients for progression of carcinoma.

Concurrent fibroadenoma and intraductal papilloma – A recurring complex lesion in a premenarcheal girl

Breast diseases are rare in childhood and adolescence, most lesions being fibroadenomas and papillomas. We report the case of an 11-year old girl with a complex breast lesion with hybrid features of fibroadenoma and intraductal papilloma with an early recurrence. Microscopically, the lesion was composed of dilated ducts showing intraluminal papillary projections with small to broad fibrovascular stalks. The typical leaf-like appearance of fibroadenoma was determined by the presence at the periphery of ducts compressed and distorted by the prominent stromal component. Despite its florid epithelial hyperplasia and mild cytological atypia (more evident in the relapse), immunohistochemical staining for p63 and smooth muscle actin highlighted a continuum outer myoepithelial layer, confirming the non-invasive appearance of the lesion. Two pathogenetic links have been hypothesized: one is based on the morphological continuum between these two entities, which may represent different evolutive stages in the same lesion; the other is based on epithelial/mesenchymal interactions. The possible malignant transformation of such complex lesion is also discussed, along with its differential diagnoses.The relevance of this case lies in its rarity, as well as in the therapeutic strategies related to its biological potential and to the necessity of a conservative treatment, due to the young age of the patient.

Mammary analog secretory carcinoma of salivary gland: Cytologic diagnosis and differential diagnosis of an unreported entity

Mammary analog secretory carcinoma of salivary gland (MASC) is a recently described salivary gland tumor. Cytologic features of this neoplasm have hitherto not been described in the literature. This report discusses the fine-needle aspiration findings of MASC and its differential diagnosis. Aspirates were richly cellular and consisted of clusters and singly dispersed cells with mild cytologic atypia. Cytoplasm was abundant and finely vacuolated. Signet ring cells were observed. Surgical resection confirmed the diagnosis of MASC.

Late presentation of metastatic smooth muscle neoplasm of the uterus with low malignant potential

A 48-year-old woman underwent total abdominal hysterectomy with conservation of the ovaries and tubes. Histology showed a well-circumscribed smooth muscle tumor with foci of degeneration (including infarct-type necrosis) but no coagulative tumor cell necrosis and only mild focal cytological atypia. She presented, 24 years later with shortness of breath and abdominal distension and underwent bilateral salpingo-oophorectomy, appendectomy, omental biopsy and para-aortic lymph node sampling. Histology showed bilateral ovarian smooth muscle tumors with no coagulative tumor cell necrosis or significant cellular atypia. The cells were mitotically active. The tumors in both ovaries were most likely secondary to the previous uterine smooth muscle neoplasm. To our knowledge, this case is the first in the literature to describe a benign cellular leiomyoma that subsequently behaved as a smooth muscle tumor of uncertain malignant potential, which recurred 24 years after the initial diagnosis.

Abstract ED01-03: Chemoprevention of lung cancer with prostacyclins or PPAR gamma agonists.

Abstract Introduction: Prostacyclin genetic overexpression or the oral prostacyclin analogue iloprost prevent development of lung cancer in a variety of murine models, including cigarette smoke exposure mice. The mechanism of action is through non-canonical PPARγ activation. PPARγ agonists also prevent development of lung cancer in experimental models. These observations have led to completed ongoing and planned phase II chemoprevention clinical trials using bronchial histology as the primary endpoint. Methods: In the completed randomized Phase II study comparing iloprost to placebo entry criteria included: current or former smoker (> 20 pack years); at least mild cytologic atypia on sputum cytology; no previous history of cancer. Autofluorescence and white light bronchoscopy was performed with 6 standard endobronchial sites biopsied, along with all other abnormally appearing areas. Subjects were then randomized to oral iloprost (in escalating doses) or placebo for 6 months and then a second bronchoscopy with repeat biopsy of all the central airway areas sampled during the first bronchoscopy, as well as any new areas suspicious for dysplasia. The predetermined primary endpoint for the study was average bronchial histologic score (based on the WHO classification of premalignant lesions) in all subjects, as well as in current and ex-smokers separately. In the ongoing study of the PPRAα agonist, pioglitazone, entry criteria, sample size and endpoints are similar. Results: For the iloprost study, 152 subjects were randomized and 125 completed both bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure and baseline histology. Endobronchial histology was summarized within patients using three separate measures: worst biopsy score (Max), dysplasia index (DI - defined as the percentage of biopsies with a score of at least 4 (mild dysplasia) or worse), and average of all biopsy scores (Avg). 74% of subjects had at least one biopsy displaying mild dysplasia (score 4.0) or worse on the initial bronchoscopy. A reproducibility study with two independent pathologists demonstrated that 85% of readings were within one histologic grade. Baseline histology was significantly worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). Former smokers receiving oral iloprost exhibited a significant improvement in Avg (0.41 better, p=0.010), Max (1.10 units, p=0.002), and an improvement in DI (12.45%, p=0.006). No histologic improvement occurred in current smokers. Proliferation by Ki-67 index was a secondary endpoint and demonstrated no change with iloprost administration. There were no differences in dropout rates or SAEs between treatment groups. In the ongoing pioglitazone study - patients have been enrolled and dropout rates are also very low. Conclusions and Future Directions: Oral iloprost significantly improved endobronchial dysplasia in former heavy smokers with sputum dysplasia. Unfortunately, the oral iloprost studied is no longer available commercially. Since the ultimate goal is to prevent lung cancer and the groups at highest risk and greatest numbers are resected stage I lung cancer and head and neck cancer patients. We are planning a randomized phase II trial in resected stage I NSCLC and SCCHN patients. The study drug will be a new oral prostacyclin or to placebo for one year with bronchial biopsies at times 0, 6 month and 12 months. CT scan will also be obtained at these times with bronchial histology as primary endpoint. When the pioglitazone study and this study are completed, a phase III randomized trial with prevention of secondary lung cancer as the primary endpoint in contemplated. Disclosures: RLK, YEM and MWG hold a patent for the use of prostacylin analogs for the prevention of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr ED01-03.

Abstract PL04-02: Oral iloprost for the chemoprevention of lung cancer: A multicenter, SPORE-initiated trial

Abstract Background: Tissue microarray studies have shown that the majority of NSCLC have decreased expression of prostacyclin synthase (PGIS) and prostacyclin supplementation (genetic overexpression and the oral prostacyclin analogue iloprost) chemoprevent lung cancer in a variety of murine models, including cigarette smoke exposure. Based on these promising results, a multi-center, double-blind, placebo controlled, phase II trial of iloprost in subjects at increased risk for lung cancer conducted at SPORE in lung cancer sites. Methods: Subjects were selected for the trial if they meet the following criteria: current or former smoker (> 20 pack years); at least mild cytologic atypia on sputum cytology; no previous history of cancer. Fluorescent bronchoscopy was performed with 6 standard endobronchial sites biopsied, along with all other abnormally appearing areas. Subjects were then randomized to oral iloprost (in escalating doses) or placebo for 6 months and then a repeat bronchoscopy with biopsy of all the central airway areas sampled on the first bronchoscopy. The primary endpoints for the study are bronchial histology and Ki-67 labeling index. Results: For the iloprost study, 152 subjects were randomized and 125 completed both bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure and baseline histology. Endobronchial histology was summarized within patients using three separate measures: worst biopsy score (Max), dysplasia index (DI - defined as the percentage of biopsies with a score of at least 4 (mild dysplasia) or worse), and average of all biopsy scores (Avg). 74% of subjects had at least one biopsy displaying mild dysplasia (score 4.0) or worse on the initial bronchoscopy. A reproducibility study with two independent pathologists demonstrated that 85% of readings were within one histologic grade. Baseline histology was significantly worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). Former smokers receiving oral iloprost exhibited a significant improvement in Avg (0.41 better, p=0.010), Max (1.10 units, p=0.002), and an improvement in DI (12.45%, p=0.006). No histologic improvement occurred in current smokers. Proliferation by Ki-67 index was a secondary endpoint and demonstrated no change with iloprost administration. There were no differences in dropout rates or SAEs between treatment groups. Analyses for other biomarkers in iloprost samples (including urinary prostaglandin metabolites, miRNAs, and EMT markers) are in progress. Conclusions: Oral iloprost significantly improves endobronchial dysplasia in former smokers and deserves further study to determine if it can prevent the development of lung cancer. Citation Information: Cancer Prev Res 2011;4(10 Suppl):PL04-02.

Melanocytes in nonlesional sun-exposed skin: A multicenter comparative study

There are limited data regarding melanocyte density and distribution on sun-exposed skin of the head and neck, in particular, comparing morphology (hematoxylin-eosin [H&E] staining) and immunohistochemistry (Melan-A staining) on formalin-fixed tissue. Furthermore, comparisons of melanocyte density between distinct geographic populations have not been made using these methods. This information would be useful for physicians who use histologic criteria to diagnose and treat lentigo maligna. We aimed to characterize the density and distribution of melanocytes using Melan-A and H&E stains on nonlesional sun-exposed skin of the face and neck, and compare the results between patients seen in Florida and Minnesota. We also aimed to quantify the presence and extent of features considered characteristic of melanoma in these noncancerous specimens of sun-damaged skin. The overall goal was to be able to provide this information to physicians who perform histopathologic interpretations of skin biopsy specimens to potentially prevent the overdiagnosis of melanoma. In all, 100 patients undergoing Mohs micrographic and reconstructive surgery for basal cell and squamous cell carcinoma were enrolled, 50 each at the two sites. Permanent tissue sections were prepared from sun-exposed skin without clinical lesions. Melanocyte density and distribution were quantified. The overall median and 90th percentile, respectively, of melanocytes per high-power field was 9 and 14 on the H&E-stained sections and 11 and 19 on the Melan-A-stained sections. The means were 9.3 and 12.0, respectively (P < .001). There was evidence that melanocyte densities were higher in patients in Florida than in Minnesota, at least using H&E staining. There was evidence of lower melanocyte densities with increasing age, more so for Melan-A than H&E staining, and higher densities in men using Melan-A. Confluence was noted in 24% of cases using H&E and 45% using Melan-A. More than two thirds of these were classified as having mild confluence, whereas the others demonstrated higher amounts of confluence (3-8 melanocytes). Only 37 patients had a follicle present; of these, 7 patients had follicular extension although this did not extend beyond 1 mm in depth. Cytologic atypia was noted in 19 of the 100 patients; pagetoid spread was found in 3. This was a selected population of patients; results may not be generalizable to the wider population. Variables such as contours of the epidermis (rete density), density of hair follicles, and epidermal thickness may affect the reproducibility of the results. Melanomas were not included for comparison. Relatively high melanocyte density, mild to moderate confluence of melanocytes, focal pagetosis, superficial follicular extension (<1.0 mm), and mild or moderate cytologic atypia may be observed in the absence of a melanocytic neoplasm. It is important for physicians to be aware of these findings so that such features are interpreted appropriately when making a histologic assessment that may ultimately influence therapy and outcome.

Abstract LB-90: Oral iloprost improves endobronchial dysplasia in former smokers

Abstract Introduction: Prostacyclin supplementation by either genetic overexpression or the oral prostacyclin analogue iloprost prevents development of lung cancer in a variety of murine models, including cigarette smoke exposure. We conducted a multi-center, double-blind, placebo controlled, phase II trial of iloprost in subjects at increased risk for lung cancer. Methods: Entry criteria included: current or former smoker (&amp;gt; 20 pack years); at least mild cytologic atypia on sputum cytology; no previous history of cancer. Autofluorescence and white light bronchoscopy was performed with 6 standard endobronchial sites biopsied, along with all other abnormally appearing areas. Subjects were then randomized to oral iloprost (in escalating doses) or placebo for 6 months and then a second bronchoscopy with repeat biopsy of all the central airway areas sampled during the first bronchoscopy, as well as any new areas suspicious for dysplasia. The predetermined primary endpoint for the study was average bronchial histologic score (based on the WHO classification of premalignant lesions) in all subjects, as well as in current and ex-smokers separately. Results: The accrual goal of 152 subjects was reached and 125 completed both bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure and baseline histology. Endobronchial histology was summarized within patients using three separate measures: worst biopsy score (Max), dysplasia index (DI – defined as the percentage of biopsies with a score of at least 4 (mild dysplasia) or worse), and average of all biopsy scores (Avg). 74% of subjects had at least one biopsy displaying mild dysplasia (score 4.0) or worse on the initial bronchoscopy. A reproducibility study with two independent pathologists demonstrated that 85% of readings were within one histologic grade. Baseline histology was significantly worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). Former smokers receiving oral iloprost exhibited a significant improvement in Avg (0.41 better, p=0.010), Max (1.10 units, p=0.002), and an improvement in DI (12.45%, p=0.006). No histologic improvement occurred in current smokers. Proliferation by Ki-67 index was a secondary endpoint and demonstrated no change with iloprost administration. There were no differences in dropout rates or SAEs between treatment groups. Conclusions: Oral iloprost significantly improves endobronchial dysplasia in former smokers and deserves further study to determine if it can prevent the development of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-90. doi:10.1158/1538-7445.AM2011-LB-90

Severe architectural disorder is a potential pitfall in the diagnosis of small melanocytic lesions

Little is known about the significance of severe architectural disorder in small melanocytic lesions with features of dysplastic nevi (DN). Using previously reported criteria, 355 consecutive DN were scored for architectural disorder and cytologic atypia. The DN were classified according to their size as small (equal or less than 3 mm) or large (greater than 3 mm). Of these 136 (38.3%) DN were classified as small. Grades of architectural disorder and cytologic atypia were equally distributed in small and large DN. Forty lesions were diagnosed as dysplastic nevi with severe architectural disorder (DNSAD). Thirteen DNSAD were small; of these, 84.6% were junctional. DN showing only mild to moderate architectural disorder were found to be predominantly compound. DN with severe cytologic atypia were mainly large (8/10 cases) with no particular type (junctional or compound) predominance. Seven cases displayed both severe architectural disorder and severe cytologic atypia; only one of these cases (a junctional lesion) measured less than 3 mm. Small melanocytic lesions displaying severe architectural disorder are mainly junctional and tend to show only mild cytologic atypia. Caution is needed when interpreting the degree of architectural disorder in these small melanocytic lesions, in order to avoid overdiagnosis of melanoma.

9p21 index as estimated by dual-color fluorescence in situ hybridization is useful to predict urothelial carcinoma recurrence in bladder washing cytology

Recent studies have shown that chromosome 9p21 locus is frequently deleted in the early stages of urothelial carcinogenesis. To study the predictive value of the 9p21 aberrations in recurrence of urothelial carcinoma of the urinary bladder, we applied dual-color fluorescence in situ hybridization for 9p21 and chromosome 9 centromere to the bladder washing cytology samples that were obtained from the patients with urothelial carcinoma of the urinary bladder treated by transurethral resection. For the evaluation, the 9p21 index was defined as the ratio of the mean number of 9p21 signals per nucleus for that of the chromosome 9 centromere signals per nucleus in each of the bladder washing cytology samples. The 9p21 index values of the bladder washing cytology samples with no (G0) cytologic atypia were significantly higher than those of the bladder washing cytology samples with moderate (G2) (P < .01) and severe (G3) (P < .001) cytologic atypia, but the index values did not statistically differ from those of the bladder washing cytology samples with mild (G1) cytologic atypia. Recurrence-free survival in the patients with a low 9p21 index value (<0.9) was significantly poorer in comparison with the patients with a high 9p21 index value (>0.9). Furthermore, 2 patients of bladder washing cytology G1 with a low 9p21 index value recurred much sooner than the other patients of the bladder washing cytology G1 category. These findings indicate that a decreased 9p21 index value is associated with recurrence of urothelial carcinoma of the urinary bladder, and the 9p21 index may be useful as a marker to identify patients with elevated risk of recurrence of urothelial carcinoma of the urinary bladder.

Anastomosing Hemangioma of the Genitourinary Tract

We describe 6 cases of a poorly recognized vascular neoplasm that can simulate angiosarcoma. Cases of a rare vascular tumor with a proclivity for the genitourinary tract encountered in our consultation material were prospectively collected between the year 1999 and 2008. Follow-up information was obtained when possible. There were 6 tumors from 4 men (66%) and 2 women, ranging in age from 49 to 75 years (median, 59.5) involving the kidney and renal hilum (4, 66%) and testis (2). Tumors ranged from 1.3 to 1.7 cm (median, 1.6 cm) and were grossly well-marginated with a hemorrhagic mahogany spongy appearance. Microscopically, at low power they had a loosely lobulated architecture and were associated with a medium-caliber vessel (5/6, 83%). Most kidney (3/4, 75%) tumors showed minor extensions into adjacent adipose tissue. At higher magnification, the tumors consisted of anastomosing sinusoidal capillary-sized vessels with scattered hobnail endothelial cells within a framework of nonendothelial supporting cells. There was a minimal inflammatory backdrop consisting of lymphocytes but not plasma cells or acute inflammation. Mitoses were absent (5/6, 83%) or rare (1 case; in supporting cells). There was mild cytologic atypia in one of the cases but no multilayering of endothelial cells in any case. Vascular thrombi were typical (5/6, 83%) and the lesions had zones of central sclerosis with focal necrosis (5/6, 83%). Two (33%) tumors featured prominent extra-medullary hematopoiesis and 2 tumors (33%) had striking hyaline globules reminiscent of those seen in Kaposi's sarcoma. Immunohistochemistry was available on some cases and the lesions stained with CD34, CD31, and FVIII but not human herpes virus type 8, keratin AE1/3, epithelial membrane antigen, HMB45, placental alkaline phosphatase, or human chorionic gonadotropin. In all but one submitted consultation, the possibility of angiosarcoma had been raised based on the anastomosing vascular pattern. On follow-up, there were no recurrences or metastases in 5 cases (range: 8 to 36 mo; median 12 mo, mean 15 mo), and 1 patient was lost to follow-up. Anastomosing hemangioma of the genitourinary tract is a rare neoplasm displaying some overlapping features of both sinusoidal hemangioma and hobnail hemangioma of soft tissue and skin. However, in our opinion, it is a unique neoplasm with a proclivity for the kidney. Its anastomosing appearance can lead to concern for angiosarcoma but, despite small numbers and limited follow-up in our series, evidence to date supports that the lesion is benign.

Intraductal tubular adenoma (pyloric gland‐type) of the pancreas: a reappraisal and possible relationship with gastric‐type intraductal papillary mucinous neoplasm

Intraductal tubular adenoma (ITA) is an uncommon intraluminal polypoid lesion that occurs in the main pancreatic duct and involves the main pancreatic duct in the region of head or body. Three cases of ITA are presented, the literature reviewed and their association with intraductal papillary mucinous neoplasm (IPMN) is postulated. ITA is composed of tightly packed tubular structures with focal cystic dilation and papillary areas lined by gastric/pyloric epithelium showing minimal to mild cytological atypia. Pancreatic intraepithelial neoplasia (PanIN) 1A and B was present in smaller ducts of all cases. In addition, in the cases in this report and 50% of cases reported in the literature, an associated gastric-type IPMN was present in the same duct as the ITA or in adjacent ducts. The coexistence of ITA and IPMN and the similarities of their epithelial lining (gastric/pyloric mucosa) suggest a possible pathogenic link. ITA can occur without (type A) or with (type B) an associated gastric-type IPMN. ITA could represent a localized, polypoid form of gastric-type IPMN.It is a benign lesion with no evidence of invasion and no direct tumour-related deaths. Its relationship to intraductal tubular carcinoma remains to be elucidated.

Spontaneous Pneumothorax as an Initial Manifestation of Metastatic Papillary Thyroid Carcinoma

Spontaneous pneumothorax occurs in a variety of lung diseases. Primary or metastatic lung cancers are rare, but important causes of pneumothorax. We report here on a case of pulmonary metastasis of thyroid papillary carcinoma that initially presented as spontaneous pneumothorax. A 32-year-old male with no history of thyroid disease underwent wedge resection of the lung due to recurrent pneumothorax. Histologically, the pleura and subpleural lung parenchyma revealed several micronodular lesions and randomly scattered glandular structures with mild cytological atypia. The cells were characterized by their overlapped hypochromatic nuclei with longitudinal grooves and inconspicuous nucleoli. On the additional sections, we found a few intranuclear inclusions and colloid-like material in the follicular structures. The glandular cells were immunoreactive for thyroglobulin, TTF-1, CK 7 and HMW-CK and they were focally immunoreactive for EMA, but they were negative for S100, chromogranin and CEA. The Ki-67 labelling index was 4%. Neck ultrasonography revealed an ill-defined hypoechoic nodule in the left lobe of the thyroid. The diagnosis of conventional, classical papillary carcinoma was made by both the cytology and the total thyroidectomy specimen. Pathologists should conduct a through histologic examination for the patients with recurrent spontaneous pneumothorax to search for the underlying causes.

Inflammatory Myofibroblastic Tumor Presenting With Esophageal Obstruction and an Inflammatory Syndrome

Inflammatory myofibroblastic tumor is a rare neoplasm of intermediate malignant potential. Although inflammatory myofibroblastic tumor occurs at multiple anatomic locations, an esophageal lesion is extremely rare. We describe a 43-year-old man who presented with severe dysphagia and an inflammatory syndrome, secondary to esophageal inflammatory myofibroblastic tumor. The patient was treated successfully with esophagectomy and remains disease free at 1 year. This case illustrates the complexities involved in managing a large esophageal myofibroblastic tumor and highlights that esophagectomy, rather than enucleation, should be the treatment of choice.

Penile Carcinoma Originating From Lichen Planus on Glans Penis

A 53-year-old man presented to the urologic department with a small tumor on the glans penis. He had been receiving dermatologic treatment of lichen planus on the glans penis for 10 years. On physical examination, the tumor displayed an irregular surface. Because of a suspicion for malignancy, a biopsy was performed. The pathologic diagnosis was squamous cell carcinoma; therefore, partial penectomy was performed. The detailed pathologic findings revealed that the white raised areas adjacent to the tumor consisted of lichen planus with mild cytologic atypia. The final pathologic diagnosis was squamous cell carcinoma (pT1N0M0) originating from lichen planus. No recurrence had been seen as of 4 years postoperatively.

Atypical Genital Nevi

Atypical genital nevi are rare melanocytic lesions that most commonly arise on the vulva of young women. They are currently regarded as nevi of special sites, in that despite histologically worrisome features, their clinical behavior is reportedly benign. However, only few studies with limited follow-up data are available. To better characterize the clinical presentation and behavior of these lesions and to further delineate their histologic features, we retrieved 56 atypical genital nevi arising in the lower female genital tract from our departmental and consultation files. The 56 lesions arose in 55 female patients with a median age of 26 years (range, 6 to 54 y). The dominant histologic feature was a lentiginous and nested junctional component composed of prominent round or fusiform nests, which often showed retraction artifact and/or cellular dyscohesion. Cytologic atypia was mild in 11 cases (20%), moderate in 34 (60%), and severe in 11 (20%). Ten cases (18%) showed focal pagetoid spread, with extension to the granular layer and stratum corneum in 1 case. The atypical junctional melanocytic proliferation was associated with a large common dermal nevus component that dominated the lesion in 26 cases (46%). Adnexal spread (46%) and nuclear atypia of melanocytes situated in the superficial dermis (39%) were relatively common, but dermal mitoses (7%) were uncommon and maturation was present in all cases. A broad zone of dense eosinophilic fibrosis within the superficial dermis was a frequent finding (41%). Clinical follow-up was available in 45 cases (80%) with a median follow-up period of 3.5 years (range, 1 to 16 y). Only 1 lesion recurred, 1.5 years after the initial excision. The original nevus in this patient had only mild cytologic atypia and was present at the margins of excision. The recurrent/persistent nevus was reexcised, and there was no further clinical recurrence in 11.5 additional years of follow-up. Our data support the hypothesis that atypical genital nevi have a benign clinical course despite their occasionally striking cytologic and architectural atypia. Awareness and recognition of this group of melanocytic lesions is important to avoid over diagnosis as melanoma with subsequent wide excision and possibly sentinel lymph node biopsy.

Prostatic ductal adenocarcinoma presenting as a urethral polyp: a clinicopathological study of eight cases of a lesion with the potential to be misdiagnosed as a benign prostatic urethral polyp

Centrally located prostatic ductal adenocarcinoma can present as a single urethral polyp mimicking a benign polyp. Such lesions have not been formally studied. Clinicopathological and immunohistochemical findings of eight cases were analysed. Patients (mean age 76 years) presented with urinary symptoms and haematuria. Mean serum prostate specific antigen (PSA) was 7.01 ng/mL (range 1.04-21). Single small polyps were seen on cystourethroscopy with a clinical diagnosis of benign polyps. The most common architectural patterns were cribriform and papillary. Five cases had mild cytological atypia, three of which were initially diagnosed as benign prostatic urethral polyps. All cases were positive for PSA and 34betaE12. Seven cases tested were positive for AMACR (a-methylacyl-CoA racemase), p63 and cytokeratin (CK) 7 and 70% for CK20. Proliferative activity defined as Ki-67 labelling index was high (mean 26%, range 20-35%). Adenocarcinoma, predominantly ductal, was found in other specimens in four patients. Centrally located prostatic ductal adenocarcinoma has the propensity to mimic benign urethral polyps clinically and histopathologically. Basal cell immunostaining may not help with this distinction but AMACR is useful. Prominent glandular complexity including cribriform patterns, nuclear pseudostratification, at least mild atypia and a high Ki-67 index distinguish these lesions from prostatic urethral polyps.

P16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix: correlation with human papillomavirus detection.

● Context.—Atypical immature squamous metaplasia (AIM) of the cervix is a loosely defined entity characterized by immature metaplastic cells with mild cytologic atypia. Objective.—To examine whether a combination of immunostaining for p16 and Ki-67 could be used to stratify AIM cases into 3 categories: benign, cases with nondiagnostic atypia, and high-grade squamous intraepithelial lesion (HSIL). Design.—The study consisted of 37 cases of AIM, 23 cases of benign cervical mucosa (NEG), and 36 cases of HSIL. All cases were tested for high-risk human papillomaviruses using SPF 10 polymerase chain reaction and immunostained for p16 and Ki-67. Results.—All cases of HSIL were positive for both p16 and Ki-67. All but 2 benign control cases were negative for both p16 and Ki-67. Seven cases of AIM (19%) displayed a pattern of immunostaining identical to HSIL, and these most likely represent a spectrum of HSIL. A total of 54% of cases of AIM were negative for both p16 and Ki-67, consistent with benign reactive atypia. Two AIM cases (5%) were negative for p16 and positive for Ki-67 in the area adjacent to an ulcer, representing regeneration. Finally, 22% of AIM cases were positive for p16 and negative for Ki-67; such cases may represent a precursor of HSIL or, alternatively, a regressing HSIL. Conclusion.—The combination of immunostaining for p16 and Ki-67 is helpful in limiting of the number of cases with nondiagnostic atypia of the cervix. (Arch Pathol Lab Med. 2007;131:1343–1349)

Giant atypical carcinoid of the liver with vascular metastases and local sinusoidal invasion: a case report

We present the case of a 46 year old woman with a giant, 23-centimeter, atypical carcinoid of the liver. A primary site for this neoplasm could not be identified despite multiple radiographic imaging studies, including a somatostatin scan, and a thorough inspection of the bowel during surgical resection of the lesion. Histologically, the tumor displayed mild cytologic atypia, abundant necrosis, and intravascular metastases, the last feature of which was identified by immunohistochemical markers for chromogranin and synaptophysin. Also described is the unusual sinusoidal infiltration, or "spillage," of tumor cells into the surrounding liver parenchyma, a feature that has not been described as far as we are aware but may suggest an aggressive clinical course. Even though an exact definition of atypia for these lesions apparently does not exist at this point, the multiple atypical features in this case strongly suggest the diagnosis of atypical carcinoid of the liver, thus far an altogether rare and vaguely reported entity. As more cases arise in the medical literature, it may be worthwhile to establish a set of guidelines to define atypical hepatic carcinoids and other gastrointestinal carcinoids, although survivorship data thus far indicates no significant difference in the prognosis between typical versus atypical variants.

Cellular Neurothekeoma: Detailed Characterization in a Series of 133 Cases

Cellular neurothekeomas are distinctive benign cutaneous tumors of uncertain histogenesis. As relatively few cases have been reported, their clinical features and morphologic spectrum remain incompletely defined, and the significance of atypical histologic features is uncertain. This study examined the clinicopathologic and immunohistochemical features of 133 cellular neurothekeomas received between 1987 and 2003. There was a 1.8:1 female predominance, with a mean age of 25 years (84% <40 y). Mean tumor size was 1.1 cm (range: 0.3 to 6 cm; 90% <2 cm). The tumors arose most often on the upper limb (35%) or head and neck (33%). Fifty-two percent of the tumors were limited to the dermis, and 48% also involved superficial subcutaneous tissue. In 30% of cases, neurothekeoma was suggested by the referring pathologist; the most common other diagnoses offered were plexiform fibrohistiocytic tumor, benign fibrous histiocytoma, and a low-grade sarcoma. Histologically, most cases were poorly marginated; 33 (25%) infiltrated fat, and 10 (8%) entrapped skeletal muscle (all but 1 situated on the face). Nearly all tumors had a lobulated or micronodular architecture and were composed of nests and bundles of epithelioid to spindled cells with palely eosinophilic cytoplasm, often separated by dense hyaline collagen; 17 (13%) showed focally sheetlike areas, and 5 (4%) were notably plexiform. Myxoid stroma was observed in 38 (29%) tumors; 11 (8%) were predominantly myxoid. Five (4%) showed marked stromal hyalinization. Osteoclastic giant cells were seen in 20 (15%) cases. The mean mitotic rate was 3 per 10 high power fields; 28 (21%) had > or =5 per 10 high power fields. Most tumors showed mild cytologic atypia in the form of nuclear variability and small nucleoli; 33 (25%) contained notably pleomorphic cells. All tumors were reactive for NKI-C3, 110/123 (89%) expressed neuron-specific enolase, 73/127 (57%) showed at least focal staining for smooth muscle actin, and only 1 was focally desmin positive. All tumors were negative for S-100 protein. Follow-up ranged from 5 to 146 months (mean 44 mo). Ten tumors recurred locally (7 situated on the face), after a mean of 18 months; tumor had been marginally excised or had involved excision margins in all cases with available information. No other clinical or pathologic features correlated with recurrence. Cellular neurothekeomas have a predilection for the upper limbs and head and neck of pediatric and young adult females and rarely recur following incomplete excision. There is no good evidence that these lesions show nerve sheath differentiation and the nomenclature will likely change when the tumor cell lineage is better defined. Atypical histologic features (including pleomorphism, infiltration of subcutis, and a high mitotic rate) seem to have no clinical significance.