Differentiated squamous intraepithelial neoplasia associated with squamous cell carcinoma of the anal canal.

AIMS: Differentiated squamous intraepithelial neoplasia (DSIN) has been described in several sites, including the upper aerodigestive tract and vulva, so this study investigated whether it also occurred in the anal canal. METHODS AND RESULTS: All cases of squamous cell carcinoma (SCC) involving the anal canal diagnosed between 2009 and 2015 at our institution were reviewed. Eighty-six cases were included, and 13 (15%) showed features consistent with DSIN: 10 were 'pure' DSIN, and three were 'mixed' DSIN and squamous intraepithelial lesion. DSIN was characterized by atypical keratinocytes limited to the basal/parabasal layers, acanthosis, and a 'cobblestone' appearance. Among specimens with pure DSIN, the surface was flat in eight cases. In five cases, the DSIN was extensive, and associated with deeply invasive SCC requiring radical surgical resection. Immunohistochemically, the epithelia showing changes consistent with DSIN were p16-negative, whereas the invasive component was p16-positive in 12 cases. Both Ki67 and p53 showed strong nuclear positivity in the basal/parabasal layers of DSIN. CONCLUSIONS: Invasive SCC associated with DSIN often presents at an advanced stage of disease, requiring radical surgical treatment. The neoplastic changes in DSIN are limited to the basal/parabasal layers, which may account for the negative diagnoses by anal cytopathology and late clinical diagnosis. The recognition of anal DSIN is important in order to avoid underdiagnosis in superficial biopsies.

Perineural invasion on biopsy is associated with upstaging at radical prostatectomy in Gleason score 3 + 4 = 7 prostate cancer.

This study assesses if perineural invasion (PNI) detected on biopsy with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill-defined glands [IDG], fused, cribriform, and glomerulations) were also assessed. Clinical information, GS and stage after RP were retrieved from the medical records. 45 % (69/154) of patients were upstaged (≥pT3) and 29 % (44/154) were upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7). There was higher %PNI in upstaged patients (12.1 % ± 1.8 vs. 7.1 % ± 1.5, P = 0.03) with a significant correlation between %PNI and ≥pT3 (r = 0.178, P = 0.027). After multivariate analysis, only cribriform formations were significantly associated with upstaging (P = 0.009). The presence of PNI in biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker predictor of ≥pT3 disease than cribriform morphology.

Multi-parametric (mp) MRI of prostatic ductal adenocarcinoma.

BACKGROUND: Prostatic ductal adenocarcinoma (DCa) is an aggressive variant of conventional adenocarcinoma (CCa) with mixed DCa and CCa tumors comprising up to 5% of all prostate cancers. DCa may be underestimated on T2-weighted (T2W) MRI. This study assessed the mp-MRI appearance of DCa as compared with CCa. METHODS: With research ethics board approval, we identified 38 patients who underwent mp-MRI (T2W, DWI, and DCE) and radical prostatectomy (RP) between 2012 and 2014. Eight DCa in 8 patients and 39 CCa tumor foci in 30 consecutive patients were identified. Tumor volume, apparent diffusion coefficient (ADC;10(-3) mm(2) /s), and time-signal intensity (SI) curves were calculated. Parametric data were compared using the Kruskal-Wallis test and univariate regression. Time-SI curves were compared using the chi-square test. RESULTS: Tumor volumes were: 1.62(±1.02) for DCa, 1.03(±0.54) for Gleason 9, 0.88(±0.93) for Gleason 7/8, and 0.26(±0.14) mL for Gleason 6. There was no difference in size between DCa and Gleason 9 (P = 0.22); however, DCa were larger than Gleason 7/8 (P = 0.03) and Gleason 6 (P = 0.003) tumors. ADC values were: 0.789(±0.22) for DCa, 1.01(±0.19) for Gleason 9, 0.992(±0.23) for Gleason 7/8 and 1.389(±0.41) 10(-3) mm(2) /s for Gleason 6 tumors. There was no difference in ADC between DCa and Gleason 9 (P = 0.14) or Gleason 7/8 (P = 0.055) tumors. There was a difference in ADC for DCa and Gleason ≥7 CCa compared to Gleason 6 tumors, (P < 0.001 and P = 0.012). All DCa demonstrated type III time-SI curves. Gleason ≥ 7 tumors demonstrated type II/III curves. Gleason 6 tumors demonstrated Type I/II time-SI curves. There was no difference in curve type between groups, (P = 0.18). CONCLUSION: Although DCa mimics Gleason score 3 + 3 = 6 tumor at T2W MRI; DCa resembles Gleason ≥7 CCa on mp-MRI.

Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation.

OBJECTIVE: To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. METHODOLOGY: Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. RESULTS: Nine of the 62 pRCCs (14.5%) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4% (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). CONCLUSIONS: Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. KEY POINTS: • A minority of pRCCs demonstrate intracellular lipid in CS-MRI. • Quantitatively, intracellular lipid in pRCCs is minimal (<25%). • Intracellular lipid in pRCCs are from clear cell heterogeneity or foamy histiocytes. • pRCCs with intracellular lipid are heterogeneously hyperintense at T2W-MRI. • pRCCs that are homogeneously hypointense at T2W-MRI do not contain intracellular lipid.

Lymphatic endothelial cancerization in papillary thyroid carcinoma: hidden evidence of lymphatic invasion.

We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework.

Nested and microcystic variants of urothelial carcinoma displaying immunohistochemical features of basal-like urothelial cells: an immunohistochemical and histopathogenetic study.

Nested/microcystic (NV/MV) urothelial carcinoma (UC) variants are associated with mild cytologic atypia and commonly present at high-stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/MV and three inverted papilloma (IP) were immunostained for CD44, cytokeratin 5 (CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high-grade UC including 14 superficial and 6 muscle-invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/MV and some invasive high grade UC. Other basal cell markers (CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance.

Histological subtypes of prostatic cancer: a comparative survival study.

INTRODUCTION: Variant histological subtypes of prostatic cancer occur uncommonly and are associated with poor survival, as has been ascertained through limited series and case reports. Here a population-based analysis of prostatic cancer is provided, to better analyze the survival behavior of these subtypes. MATERIALS AND METHODS: The American SEER registry was used to review prostatic cancer diagnosed from 1988 to 2003, classified according to the International Classification of Diseases for Oncology. Kaplan-Meier and proportional hazards analyses were performed on adenocarcinomas and five infrequent variant subtypes to determine their overall survival behavior, allowing corrections for follow up inequity, age, stage, histological grade, and year of diagnosis. RESULTS: A total of 455,296 cases of prostatic cancer were reviewed, of which over 99% were conventional adenocarcinomas. The remaining variants studied included ductal carcinomas (0.141%), mucinous adenocarcinomas (0.103%), small cell carcinomas (0.056%), carcinosaromas (0.07%) and embryonal carcinosarcomas (0.06%). With age, stage and grade effects were corrected for in the multivariate analysis, conventional adenocarcinomas, mucinous adenocarcinomas and ductal carcinomas exhibited similar survival behavior. Small cell carcinomas and carcinosarcomas exhibited poor survival, even with correction. The embryonal variant of carcinosarcoma affected pediatric patients and had an overall survival similar to conventional prostatic cancer. Ductal carcinomas, small cell carcinomas and both types of carcinosarcoma tended to present with metastases more frequently than conventional disease. CONCLUSIONS: Prostatic cancer subtype can have a major bearing on overall survival and likely reflects intrinsic differences in biological behavior.

Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study. Development of criteria for screening the entity with prognostic significance.

AIMS: Renal epithelioid angiomyolipoma (EAML) is only described in case reports or in multi-institutional small series. The aim was to report cases seen at our institution and to perform a meta-analysis based on a literature review. METHODS AND RESULTS: Six EAML cases seen at our institution were reviewed and a meta-analysis performed using cases retrieved from a literature review. There were a total of 69 cases for review. The male:female ratio was 1:3. In the absence of areas of typical AML, useful features in distinguishing EAML from epithelial renal neoplasms include: extreme degree of cytological atypia, histiocytoid appearance, presence of melanocytic pigments, solid architecture with the absence of frequent areas of alveolar pattern, tubulo-papillary formation and scarring. A fatal outcome, distant or lymph node metastasis, venous invasion and local recurrence were considered as adverse events and occurred in 40% of cases over a period of follow-up of 3-60 months (mean 22.5 +/- 18 months). Tumours with an unfavourable outcome showing marked cytological atypia and extensive tumour necrosis were larger (135 +/- 43 mm) than those with a favourable outcome (79 +/- 50 mm) (P < 0.002), and predominantly occurred in men. CONCLUSIONS: Renal neoplasms with certain unusual features should be investigated immunohistochemically to rule out the possibility of EAML. The frequency of adverse outcome is lower in EAML than in renal cell carcinoma.

Oncocytic renal cell carcinoma with immunohistochemical properties of renal oncocytoma.

Renal oncocytoma (RO) is a characteristic benign renal tumor. The existence of malignant RO is controversial and anecdotal, partly due to a lack of specific markers for RO. With recent advances in immunohistochemistry, RO can be distinguished from other renal neoplasms with routine stains and with the aid of immunostaining. We report two cases of renal neoplasms with similar histopathological appearances. They were characterized by oncocytic cytoplasm, numerous intra-cytoplasmic vacuoles, uniform round to oval hyperchromatic nuclei with remarkably thick nuclear membranes and prominent nucleoli. The tumor cells were closely packed and disposed in an alveolar pattern. The neoplastic cells were diffusely reactive for CD117 and progesterone receptor, and diffusely or focally reactive for cytokeratin AE1/AE3, and focally reactive for cytokeratin 7, CD10, and racemase. The cells were non-reactive for renal cell carcinoma (RCC) antigen, vimentin, S100, and neuroendocrine markers. One tumor showed lymph node metastasis. Due to the remarkable cytological atypia, lymph node metastasis, and similar immunological features of RO, these two tumors likely represent a distinct subtype of RCC related to RO.

Urothelial carcinoma and prostatic adenocarcinoma presenting as collision tumors.

Urothelial carcinoma (UC) and prostatic adenocarcinoma (PAC) commonly occur in elderly patients and share common carcinogenic factors that could be identified in the urine. The presence of one tumor is known to be associated with an increased incidence of the other. Simultaneous occurrence of PAC and UC in the prostate is not uncommon; however, urinary bladder location of both lesions has not yet been reported. Furthermore, invasion into the urinary bladder wall by a PAC can also pose a diagnostic challenge with UC and other primary urinary bladder tumors. We report three patients presenting with UC and PAC within the urinary bladder. The patients were 80, 84 and 85 years old. All patients were diagnosed with high grade PAC and either had simultaneous at the initial diagnosis or developed UC during the follow up for PAC. Histopathological analysis pictured collision tumors consisting of an invasive component represented by high grade PAC and a superficial component composed of low or high grade UC. Both components displayed distinctive immunophenotypes: PAC was P63- /HMWCK- /PSA+ and UC was p63+/HMWCK+/ PSA-. In conclusion, awareness of this association is important in making the correct diagnosis, especially when dealing with urinary bladder biopsy material.

Immunostaining as a diagnostic aid in cytopathologic study of upper urinary tract urothelial carcinoma.

OBJECTIVE: To evaluate preoperative diagnosis of low-grade urothelial carcinoma (LGUC) and urothelial neoplasms of unknown malignant potential (UMP UN) of the upper urinary tract (UUT) and its role in disease management, especially in the context of nephron-sparing treatment possibilities. STUDY DESIGN: Wash and brush ureteral specimens of LGUC/UMP UN of the UUT with histopathologic correlation were retrieved at our institution for 7 years and studied along with 7 ureteral specimens from nonneoplastic ureteral lesions. RESULTS: Of 30 specimens from 25 LGUC/UMP UN, 5 were negative for tumor cells and 3 showed cytologic atypia. The remaining 22 contained tumor cells with characteristic features of urothelial carcinoma, including hard and soft criteria. The 4 hard criteria included branching stromal cores, dyshesive cell networks, 3-dimensional papillary clusters with stromal core and atypia associated with CK20-positive cells. The 2 soft criteria were hypercellularity and atypia in CK20-negative cells. All LGUC/UMP UN of the UUT were associated with at least 1 hard criterion or both soft criteria. CONCLUSION: Branching stromal cores, 3-dimensional papillary clusters, dyshesive cell networks and CK20-positive atypia immunostaining appear specific for LGUC/UMP UN of the UUT but are seen in few cases. Combined soft and hard criteria will increase sensitivity to 83%.

Cytologic features of benign solitary pulmonary nodules with radiologic correlation and diagnostic pitfalls: a report of six cases.

BACKGROUND: The solitary pulmonary nodule (SPN) is a common radiologic abnormality often detected incidentally. The majority of SPNs represent benign processes, including granulotmatous inflammation, bronchogenic cysts and hamartomata. However, a solitary nodule may also potentially represent an early stage of lung cancer or a metastasis. Diagnostic procedures such as percutaneous fine needle aspiration biopsy can exclude malignancy in a majority of cases and may eliminate the need for more invasive surgical procedure. Correlation of the findings on the FNAB with radiologic features is helpful in establishing the benignity. CASES: We report the cytologic features of 6 cases of benign SPN: exogenous lipid pneumonia, sclerosing hemangioma, hemartoma, bronchogenic cyst, fungal granuloma and solitary fibrous tumor. We provide radiologic correlation for each entity and discuss the diagnostic pitfalls. CONCLUSION: Cytologically, lack of nuclear atypia with bland chromatin is useful in separating benign from malignant SPN. Radiologically, smaller lesions with smooth, well-defined margins and calcifications are more likely to be benign. Our cases illustrate the cytologic and immunohistochemical features that can help to make a more precise diagnosis. The identification of these features, when correlated with imaging findings, allows the cytopathologist to better approach the SPN.

Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity.

AIMS: Clear cell renal cell carcinoma (CRCC) with diffuse immunoreactivity for CK7 is described. METHODS: All cases of CRCC, measuring 20 mm or less in diameter over a period of 10 years, were examined. Areas of regenerative epithelial cell nests (REC) were also examined. RESULTS: Fifteen specimens containing 29 nodules were diagnosed as CRCC due to the characteristic clear cytoplasm. Of these 29 nodules, 21 showed diffuse CK7 positivity while eight showed CK7 negativity. The CK7 positive CRCC measured less than 16 mm and contained varying proportions of tumour cells with chromophil cytoplasm. Architecturally, CK7 positive CRCC consisted of cysts and solid cell nests with tubulo-acinar formations or papillary formations. Immunostaining for AMACR, CD10 and RCC showed negative or focal reactivity in the CK7 positive CRCC, frequently positive reactivity in CK7 negative CRCC and negative reactivity in REC which also displayed strong CK7 reactivity. The ten patients with 21 CK7 positive CRCC developed no metastatic disease over a follow up time that ranged from 1 to 10 years (mean of 3 years). CONCLUSIONS: CRCC characterised by diffuse CK7 positivity represents a distinct type of CRCC with characteristic histopathological and immunohistochemical features.

Calretinin and CD34 immunoreactivity of the endometrial stroma in normal endometrium and change of the immunoreactivity in dysfunctional uterine bleeding with evidence of 'disordered endometrial stroma'.

AIMS: We investigated the pattern of reactivity of calretinin and CD34 in normal and pathological endometria. METHODS: Various endometrial tissues were submitted for calretinin and CD34 immunostaining. RESULTS: Calretinin reactivity was limited to the endometrial stromal cells (ESC) of the superficial zone of the functionalis layer (FL) in the proliferative phase, and was extensive in all stages of the secretory phase. The ESC of the post-menopausal, ectopic, hyperplastic or neoplastic endometria showed negative or focal weak reactivity for calretinin. In dysfunctional uterine bleeding (DUB) with a normal or an abnormal histopathological appearance on routine stain, there were varying degrees of focal to extensive decreases in calretinin reactivity. The foci of negative calretinin reactivity in the FL displayed varying reactivity for CD34 and appeared to be continuous with the basalis layer (BL). Endometrial polyps were often reactive for CD34, but not reactive for calretinin. CONCLUSIONS: Immunostaining for calretinin and CD34 is helpful in the diagnosis of endometrial polyp and hyperplasia. In DUB, with or without abnormal histopathological findings, there were alterations of the zonal pattern of calretinin reactivity in the FL. This alteration appears to be an expansion of the stroma of the BL into the FL, resulting in a 'disordered endometrial stroma'.

Oncocytic papillary renal cell carcinoma with solid architecture: mimic of renal oncocytoma.

Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117-/PR- immunophenotype (feature shared by RCC). The CD117-/PR- ORCN also displayed alpha-methylacyl-coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.

Primary prostatic central zone adenocarcinoma.

The central zone (CZ) of the prostate is embryologically, anatomically, and histologically distinct. High-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma (PAC) are encountered in the CZ, but have not been well studied. Non-CZ PAC that spread into the CZ can mimic CZ PAC. We reviewed 300 consecutive radical prostatectomies performed for PAC to identify cases showing PAC and HGPIN in the CZ. There were nine PAC (3%) localized predominantly in the CZ, presenting as a single tumor nodule (8/9) and associated with 4.5+/-1.1 foci HGPIN in the CZ and with only 1.7+/-0.5 foci in the PZ. Of the 291 non-CZ PAC, 24 cases showed satellite tumor nodules in the CZ, and 92 cases demonstrated secondary contiguous spread to the CZ. As compared to the non-CZ PAC, CZ PAC tended to have lower tumor volume, but had higher Gleason scores (8.10+/-0.6 vs. 6.30+/-0.7, p<0.05), as well as a higher incidence of a ductal carcinoma component (6/9), higher rates of capsular penetration, positive resection margins (4/9), and seminal vesicle spread (2/9). The CZ HGPIN associated with CZ PAC demonstrated cells with prominent nucleoli and formed either slender papillary structures or cribriform/solid patterns. The correlating positive biopsy cores were from the mid portion or from base of prostate and contained foci of HGPIN in 4/7 cases. The CZ PAC is characteristically accompanied by more foci of HGPIN in the CZ than in non-CZ and is associated with high grade and high stage. Preoperative diagnosis of CZ PAC can be suspected due to the histopathological features in the biopsy and is important to improve the free surgical resection rate.

Invasive low-grade urothelial carcinoma in a bladder biopsy associated with high-stage disease and masquerading as schistosomiasis.

We present an interesting case of a 56-year-old Egyptian woman with high-grade urothelial carcinoma (HGUC) associated with schistosomiasis that appeared initially as low-grade (LGUC) disease on transurethral resection of the bladder tumor (TURBT). Areas of HGUC and tumor invasion were detected only after meticulous microscopic examination of the partial cystectomy specimen. Furthermore, there were no areas of squamous cell metaplasia identified. This case highlights one of the limitations of biopsy for determining cancer grade and stage. It also emphasizes that schistosomiasis may be associated with non-squamous cell forms of bladder cancer, the pathogenesis of which has not been fully elucidated.

Does Differentiated Squamous Intraepithelial Neoplasia Occur in the Cervix?

BACKGROUND: Invasive cervical cell squamous carcinoma (ICC) classically develops from high grade cervical intraepithelial neoplasia of usual type (uCIN). Differentiated cervical intraepithelial neoplasia (dCIN) analogue to differentiated vulvar intraepithelial neoplasia has not been described in the cervix. METHODS: A pilot case of ICC developing from dCIN with atypia limited to the basal/parabasal layers, focally associated with neoplastic spread above the parabasal layer (usual-like CIN pattern or u-like CIN) was identified. The previous cervical biopsy was under-diagnosed as low grade CIN. A total of 33 consecutive cases of ICC were reviewed to identify dCIN, u-like CIN and uCIN. RESULTS: The ICC developed from dCIN/u-like CIN in 2 patients, 46 and 47-year-old (group 1), mixed dCIN/u-like CIN and uCIN in 7 patients, 36±3-year-old (group 2) and from uCIN in 24 patients, 47±9-year-old (group 3). In group 1, focal uCIN but not connected to ICC was also seen and Pap smears showed only hyper-keratinized cells with mildly atypical nuclei. Endocervical gland involvement by CIN was absent in group 1, focal in group 2 and extensive in group 3. All cases showed diffuse p16 staining. P53 reactivity was noted in basal/parabasal in dCIN, predominantly lower and upper parts of the epithelium in groups 2 and 3, respectively. CONCLUSIONS: Totally, 27% of ICC cases had associated dCIN/u-like CIN and in younger patients than in the uCIN group. Larger studies are needed to confirm dCIN/u-like CIN as significant precursor lesions of ICC.

Laryngeal Squamous Cell Carcinomas are Commonly Associated With Differentiated Squamous Intraepithelial Neoplasia With or Without an Admixture With Usual Type of Squamous Intraepithelial Neoplasia: Clinical and Pathologic Significance.

BACKGROUND: Differentiated squamous intraepithelial neoplasia (dSIN) is a pathway in the development of invasive squamous cell carcinoma (SCC) distinct from the usual-type squamous intraepithelial neoplasia (uSIN) and has not been described in the larynx. MATERIALS AND METHODS: Sixty-nine consecutive cases of SCC were identified which included 25 dSIN, 13 uSIN, and 31 mixed dSIN+usual-like SIN (u-like SIN) cases. RESULTS: dSIN was characterized by atypical squamous cells limited to the basal/parabasal layers and u-like SIN was characterized by cytologic atypia limited to less than full thickness. Despite the lack of neoplastic involvement of the full thickness of the epithelium, these types of SIN were commonly connected with invasive carcinoma. Prior biopsies demonstrating only dSIN, without the underlying invasive SCC, were underdiagnosed in 2 cases. Because of the frequent keratinization, u-like SIN likely represents the "keratinized dysplasia" and shows changes suggestive of dSIN with upward spread of neoplastic cells into the upper layer of the epithelium. CONCLUSIONS: Laryngeal dSIN represents an important but under recognized pathway of invasive SCC development. As moderate dysplasia of uSIN type are not associated with invasive SCC, labeling u-like SIN as dysplasia of grade 2 or 3 likely leads to the controversies in the current grading systems in the upper aerodigestive system and causes confusion for clinicians.

The 3-dimensional structure of isolated and small foci of prostatic adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

BACKGROUND: Transitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. DESIGN: Twelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. RESULTS: Eight ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. CONCLUSIONS: PAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.