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Biomedical subjects

Jesse K McKenney

Publications and source records attributed to Jesse K McKenney.

14 recordsLinked to original sources

Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.

Humans↗

Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): pathology, prognosis, and proposed classification.

The occurrence of regional lymph node involvement (LNI) in patients with primary ovarian serous tumors of low malignant potential (S-LMP), although well described in the literature, continues to be problematic. Most studies indicate that LNI is not associated with an adverse prognosis, but there has not been a comprehensive study addressing the histologic patterns of LNI, the importance, if any, of classifying the type of LNI (ie, as either noninvasive or invasive in analogy to peritoneal implant classification), or the presence and significance of associated endosalpingiosis. To further evaluate LNI in S-LMP, 74 patients with ovarian S-LMP and a lymph node biopsy or sampling were studied. Thirty-one of 74 patients had LNI in pelvic (18; 58%), mesenteric/omental (9; 29%), paraaortic (8; 26%), or supradiaphragmatic (2; 6%) lymph nodes. The number of involved nodes ranged from 1 to 20 (mean, 11.1). Four patterns of LNI were identified: individual cells, clusters of cells, and simple, nonbranching papillae (28 of 31; 90%); intraglandular (21 of 31; 68%); cells with prominent cytoplasmic eosinophilia ("eosinophilic cell" pattern) (16 of 31; 52%); and micropapillary pattern (5 of 31; 16%). LNI was diffuse in at least one lymph node in 13 patients (42%) and formed nodular aggregates greater than 1 mm in 6 patients (19%). Nodal endosalpingiosis was present in 58% of cases with LNI compared with 35% without LNI (P=0.06). There was no significant difference in survival for patients with LNI compared with patients without LNI. However, the presence of discrete nodular aggregates of epithelium greater than 1 mm in linear dimension without intervening lymphoid tissue was associated with a statistically significant decreased disease-free survival when compared with other patterns of LNI (P=0.02). Nodular aggregates were strongly associated with desmoplastic fibrous stromal reaction (P=0.001) and micropapillary architecture (0.02). There was also a trend for decreased survival among patients with LNI without associated endosalpingiosis (56%) compared with patients with LNI associated with endosalpingiosis (85%) and those with endosalpingiosis only (93%). This study suggests that patients with ovarian S-LMP may be further substratified into risk categories by the presence of nodular aggregates of S-LMP in lymph nodes, a feature that is more common in cases with micropapillary architecture and associated stromal reaction in the intranodal tumor. This high risk pattern of LNI may have a predictive value similar to invasive peritoneal implants and deserves independent evaluation in future studies of S-LMP.

Adult↗

Patterns of stromal invasion in ovarian serous tumors of low malignant potential (borderline tumors): a reevaluation of the concept of stromal microinvasion.

Stromal-epithelial patterns of invasion in serous tumors of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas whereas those with either no stromal invasion or stromal microinvasion are classified as serous tumors of low malignant potential (S-LMP). The histologic features of stromal microinvasion in ovarian S-LMP have been addressed in a variety of studies, but controversy persists regarding diagnostic criteria and prognostic significance, particularly in patients with high-stage disease. In addition, a subset of otherwise typical S-LMP has patterns of invasion that are not classic destructive invasion and do not meet the current diagnostic criteria for stromal microinvasion because of either qualitative features or size restrictions. To further evaluate the full histologic spectrum of stromal-epithelial patterns of invasion in otherwise typical S-LMP, we examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO stages II, III, and IV) with stromal-epithelial alterations not meeting criteria for classic destructive invasion. This group of cases included those meeting the definition of microinvasion and a subset that would be excluded based on size measurements or unusual qualitative features, but did not exhibit significant stromal reaction. Five patterns of invasion were identified: individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, inverted macropapillae, and micropapillae. Individual, discrete aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in greatest linear dimension as measured by conventional methods. The number of discrete foci ranged from 1 to greater than 10; in 7 tumors (12%), the invasive foci were diffusely scattered throughout the stroma without discrete aggregates. These stromal-epithelial alterations were associated with disease progression and/or death due to disease in 9 of 50 (18%) patients with follow-up (mean, 92.5 mo) and were covariant with other adverse prognostic features (invasive implants, nodular lymph node aggregates, high stage, and unresectable disease). Disease progression was most strongly linked to the presence of micropapillae, but the majority of patients with adverse outcome had the more common, classic stromal-epithelial patterns associated with microinvasion (ie, individual cells, cell clusters, and simple papillae). Neither size of the largest contiguous aggregate nor extent of stromal involvement correlated with outcome. Classic microinvasion disproportionately occurred in patients presenting during pregnancy (P<0.0001), and was not associated with adverse outcome in that setting, but follow-up was limited. Based on the cumulative outcome data, the presence of stromal-epithelial patterns of invasion distinct from classic destructive invasion in otherwise typical S-LMP stratifies patients at long-term risk for disease progression, but does not warrant a diagnosis of carcinoma or a change in current management schemes. Maintaining classification as a serous tumor of low malignant potential (serous borderline tumor) with stromal invasion seems appropriate even in the presence of diffuse stromal involvement or discrete aggregates measuring greater than 3 (or 5) mm. As the stromal-epithelial alteration featuring micropapillae may represent a comparatively higher-risk lesion with a clinical course analogous to that of low-grade serous carcinoma, pathologists should identify this specific stromal-epithelial pattern in the diagnostic report until sufficient data is acquired to form more definitive conclusions regarding its prognosis.

Cystadenocarcinoma, Serous↗

The role of immunohistochemistry in the diagnosis of urinary bladder neoplasms.

The spectrum of neoplasms involving the urinary bladder is diverse, and, at times, different entities with distinct prognostic and managerial implications may have significant morphologic overlap. The presence of a neoplasm with an unusual morphologic appearance, such as an undifferentiated spindled, or plasmacytoid pattern may necessitate immunohistochemistry to establish the diagnosis. In this review, we discuss a series of distinct diagnostic scenarios, including high-grade undifferentiated carcinoma versus prostatic adenocarcinoma, enteric-type adenocarcinoma versus secondary colorectal adenocarcinoma, spindle cell proliferations, neoplasms with plasmacytoid morphology, endophytic tumors with a nested growth pattern, and flat urothelial lesions with atypia. We also discuss markers supporting urothelial differentiation in the context of a metastatic carcinoma from an unknown primary. The importance of using a morphologically derived differential diagnosis to guide the selection and interpretation of immunohistochemical studies is emphasized, and the varying utility (specificity) of the individual immunohistochemical markers within each setting is addressed.

Adenocarcinoma↗

An approach to the classification of spindle cell proliferations in the urinary bladder.

Spindle cell proliferations of the urinary bladder are uncommon but may cause significant diagnostic difficulty resulting from the degree of morphologic overlap between clinically benign and malignant lesions. These difficulties may be amplified in small biopsies because some of the more specific diagnostic features may not be present for evaluation. In addition, the number of different diagnostic terms applied to the same entity has added confusion to this diagnostic area. This review discusses the nomenclature, morphologic criteria, and immunohistochemical features used to classify spindle cell proliferations occurring in the urinary bladder, including those with myofibroblastic, smooth muscle, skeletal muscle, epithelial (sarcomatoid urothelial carcinoma), fibroblastic, and neural differentiation. A separate discussion of 5 challenging differential diagnostic scenarios is also presented.

Animals↗

Ovarian serous tumors of low malignant potential (borderline tumors): outcome-based study of 276 patients with long-term (> or =5-year) follow-up.

The natural history, classification, and nomenclature of ovarian serous tumors of low malignant potential (S-LMP) (serous tumors of borderline malignancy, atypical proliferating tumors) are controversial. To determine long-term outcome for patients with S-LMP and further evaluate whether S-LMP can be stratified into clinically benign and malignant groups, the clinicopathologic features of 276 patients with S-LMP and > or =5 year follow-up were studied. The histology of the ovarian primary, extraovarian implants, and recurrent tumor(s) were characterized using World Health Organization criteria and correlated with FIGO stage and clinical follow-up. After censoring nontumor deaths, overall survival and disease-free survival for the 276 patients was 95% (98% FIGO stage I; 91% FIGO II-IV) and 78% (87% FIGO stage I; 65% FIGO stage II-IV), respectively. Unresectable disease (P < 0.001) and invasive implants (P < 0.001) were associated with decreased survival. When compared with typical S-LMP, S-LMP with micropapillary features were more strongly associated with invasive implants (P < 0.008) and decreased overall survival (P = 0.004), but patient outcome with micropapillary S-LMP was not independent of implant type. Stromal microinvasion in the primary tumor was also correlated with adverse outcome, independent of stage of disease, micropapillary architecture, and implant type (P = 0.03). There was no association between outcome and lymph node status. Transformation to low-grade serous carcinoma occurred in 6.8% of patients at intervals of 7 to 288 months (58% > or = 60 months) and was strongly associated with increased tempo of disease and decreased survival (P < 0.001). S-LMP forms a heterogeneous group, morphologically and clinically distinct from benign serous tumors and serous carcinoma. The majority of S-LMP are clinically benign, but recurrences are not uncommon, and persistent disease as well as deaths occur. Progression to low-grade serous carcinoma is highly predictive of more aggressive disease. Other features associated with recurrent and/or progressive disease include FIGO stage, invasive implants, microinvasion in the primary tumor, and micropapillary architecture. These predictors tend to co-occur, and no single clinical or pathologic feature or combination of features identify all adverse outcomes. The small, but significant risk of progression over time to low-grade serous carcinoma emphasizes the need for prolonged follow-up in patients with S-LMP.

Adolescent↗

Endometrial adenocarcinoma associated with subtle lymph-vascular space invasion and lymph node metastasis: a histologic pattern mimicking intravascular and sinusoidal histiocytes.

Lymph-vascular space invasion has been established as an independent prognostic factor in endometrial adenocarcinoma. Despite the importance of its recognition, the histologic patterns of lymph-vascular space involvement have not been well addressed in the surgical pathology literature. We report three cases of endometrioid adenocarcinoma of the uterine corpus associated with a subtle pattern of lymph-vascular space invasion closely mimicking intravascular histiocytes. Two cases had regional lymph node metastases composed of morphologically similar cells.

Aged↗

Cutaneous angiosarcoma following breast-conserving surgery and radiation: an analysis of 27 cases.

Iatrogenic angiosarcomas (AS), following treatment of breast carcinomas and attributed to chronic lymphedema, were first described by Stewart and Treves. With emphasis on breast-conserving therapy combined with adjuvant radiation, a recently recognized form of cutaneous postradiation angiosarcoma of the breast (CPRASB) has emerged. To more completely characterize CPRASB, 27 cases were analyzed. Histologic features studied included pattern of growth (vasoformative, sieve-like, or solid), nuclear grade, necrosis, and mitotic rate. Clinical and follow-up information was obtained. The patients received relatively standard radiation treatment. The median interval to diagnosis of CPRASB was 59 months; 5 occurred in less than 3 years. Lymphedema was largely absent, and when present was only mild in nature. CPRASB was frequently multifocal at presentation (13 of 27). All tumors had a vasoformative pattern of growth; the majority (16 of 27) had areas with a sieve-like pattern. The solid pattern was less frequent (7 of 27). The majority had high-grade nuclear features (16 grade 3, 8 grade 2, 3 grade1). The mean mitotic rate was 9/10 HPF. Necrosis was rare (2 of 27). All were treated with wide excision or mastectomy. Follow-up was available on 22 of 27 cases (median 44 months). Fourteen experienced local recurrence and 6 had multiple recurrences. Metastasis was documented in 9 of 22 patients and involved lungs (6), contralateral breast (3), skeleton (2), lymph nodes (1), and soft tissue (1). Eight patients died of disease, 2 died with disease, 4 were alive with disease, and 8 are alive without disease. The median interval to death was 33.5 months. All 4 patients with disease have documented metastasis. CPRASB differs from Stewart-Treves AS by its shorter latency period and lack of association with lymphedema.

Aged↗

Basal cell proliferations of the prostate other than usual basal cell hyperplasia: a clinicopathologic study of 23 cases, including four carcinomas, with a proposed classification.

Basaloid proliferations of the prostate with morphologic patterns other than usual basal cell hyperplasia are rare, and the distinction between benign and malignant lesions has been difficult. We describe 23 such lesions and classify them into two groups: adenoid cystic-like hyperplasia and adenoid cystic or basaloid carcinoma. Adenoid cystic-like hyperplasia (n = 19) was characterized by an older age at presentation (mean, 71.8 years), transition zone location with background of nodular hyperplasia, multifocality, lobulation, circumscription, and small acini with occasional hyalinization. A cribriform pattern limited to small- and medium-sized glands, squamous metaplasia, and hypercellular myxoid stroma were occasionally seen. Adenoid cystic carcinoma (n = 3) was characterized by a younger age at presentation (mean, 46.0 years), peripheral zone involvement, and large acini that were often dilated and exhibited extensive interanastomoses, prominent intraglandular hyalinization, perineural invasion, and extraprostatic extension. Basaloid carcinoma (n = 1) showed infiltration between normal glands, perineural invasion, and extraprostatic extension but lacked a cribriform architecture. The degree of cytologic atypia and mitotic rate overlapped between the hyperplasia and carcinoma cases. Both hyperplastic lesions and adenoid cystic carcinomas showed a basal cell phenotype with strong immunoreactivity to cytokeratins 14 and 34betaE12, but the basaloid carcinoma was negative for these markers. In all cases, the proliferating basal cells were nonreactive for myoepithelial and prostatic secretory cell markers. The 8 patients with adenoid cystic-like hyperplasia with available follow-up information had no progression of disease (mean follow-up period, 8.6 years). One patient with adenoid cystic carcinoma died with widespread metastases, but the 3 other patients with carcinomas had no disease progression (mean follow-up period, 7.0 years). In conclusion, most florid basaloid proliferations of the prostate fall into one of two categories. In the first, there is a clear association with nodular hyperplasia (adenoid cystic-like hyperplasia) and, although cytologic atypia and mitoses may be seen, they are present within a lesion that retains an orderly, vaguely nodular (noninfiltrative) pattern. The second group of cases (adenoid cystic and basaloid carcinoma) shows a widespread, haphazard infiltrative growth pattern. This study suggests that adenoid cystic carcinomas are biologically indolent following prostatectomy but have a low risk of distant metastasis.

Adult↗

Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases.

The existence of a papillary lesion of the urinary bladder with a benign clinical course and recognizable morphologic features that merit the benign categorization "papilloma" has been controversial. The clinical aspects and histologic features of these lesions remain to be fully elucidated. We have studied the clinicopathologic features of 26 patients with urothelial papillomas and correlated them with outcome. Papillomas occurred in two distinct clinical settings: (1) de novo neoplasms (23/26) or (2) those occurring in patients with a known clinical history of bladder cancer ("secondary" papillomas; 3/26). Follow-up information was available in 14/23 of the de novo cases (mean = 39 mo) and in 3/3 secondary cases (mean = 24 mo). Patients with de novo papillomas had a mean age of 46 years; 16 were male and 7 were female. Twelve of 14 had a benign clinical course with no recurrences; 1 developed a recurrent papilloma at 3 years, and 1 developed a pT3a high-grade papillary urothelial carcinoma at 4 years. Patients with secondary papillomas had a mean age of 66 years; two were male and one was a female. One of these patients developed two additional recurrences, and two patients had no new recurrences. Morphologically, the papillary architecture ranged from a common simple, nonhierarchical arrangement to, infrequently, more complex anastomosing papillae with budding. The individual papillae ranged from small (most common), with scant stroma and slender fibrovascular cores, to large, with marked stromal edema and/or cystitis cystica-like urothelial invaginations. Common to all was a lining of normal-appearing urothelium without hyperplasia, maintenance of normal polarity, and frequent prominence of the umbrella cell layer. Overall, no patient with a diagnosis of papilloma died of disease; only one patient with a de novo lesion (7.0%) had a recurrent papilloma, and 1/14 (7.0%) progressed to a higher grade and stage of disease, although this patient was on immunosuppressive therapy secondary to a renal transplant. De novo urothelial papillomas occur in younger patients and usually have a benign course. Urothelial papillomas are histologically and probably biologically distinctive tumors and merit distinction from other higher risk papillary neoplasms of the urinary bladder.

Adult↗

Clear cell myomelanocytic tumor of the thigh: report of a unique case.

The clear cell myomelanocytic tumor (CCMMT) is a recently reported and very rare member of the perivascular epithelioid cell family of tumors (PEComa). All CCMMTs reported to date have occurred in or immediately adjacent to the falciform ligament/ligamentum teres. We report a case of CCMMT that occurred in the right thigh of a 43-year-old woman. Histologic examination showed the classic features of CCMMT, and immunohistochemical studies confirmed co-expression of smooth muscle actin, HMB-45, and microphthalmia transcription factor.

Actins↗

Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma.

Rhabdomyosarcomas (RMSs) are classified into embryonal (ERMS), alveolar (ARMS), and pleomorphic (PRMS) subtypes. ERMS, including botryoid variants, typically occurs in young children, ARMS typically occurs in older children and young adults, and PRMS occurs in older adults. Although ARMSs show thin fibrous bands separating nests of cells, abundant extracellular matrix production is rare in RMS. In the course of reviewing hyalinizing sarcomas we discovered a distinctive RMS in adults that closely mimicked osteosarcoma or chondrosarcoma because of the extensive matrix production. Four RMSs with hyalinized matrix were retrieved from our files. These cases were evaluated with respect to patient age and sex, tumor site and size, growth pattern, nuclear grade, cellularity, mitotic figures/20 high power fields, vascular invasion, necrosis, the presence of rhabdomyoblasts, multinucleated cells, and alveolar growth pattern. Immunohistochemistry for desmin, myogenin, MyoD1, actin, cytokeratin, S-100 protein, collagen II, and CD99 was performed. Reverse transcriptase polymerase chain reaction for the ARMS-associated PAX3/FKHR and PAX7/PKHF was also performed on three cases. The cases involved the forearm, hand, orbit, and nasopharynx of a 40-year-old woman, a 50-year-old man, an 18-year-old man, and a 21-year-old man, respectively. The tumors ranged from 3.7 to 8 cm and consisted of lobules and infiltrating cords of small round malignant cells embedded in a densely hyalinized matrix having both a chondroid and osteoid-like appearance. No definite lacunae or matrix calcification was present. An alveolar pattern was only present focally, and tumor giant cells were not present. One case had a single focus of rhabdomyoblastic differentiation with strap cells. Mitotic activity was >20 mitotic figures/20 high power fields in three of four cases. Immunohistochemically, one case strongly expressed desmin, whereas three cases expressed it focally, with a dot-like pattern. Myogenin was only focally positive, but MyoD1 was present in nearly every cell of each case. Two cases expressed actin and one expressed CD99. No case expressed cytokeratin, S-100 protein, or collagen II. Only one case contained adequate RNA for reverse transcriptase polymerase chain reaction, and this case was negative for the ARMS-associated gene fusions. Follow-up showed one patient to be dead of metastatic disease at 60 months despite intensive therapy, another patient to be disease free at 26 months, and the third patient to be disease free at 5 months. The fourth case is recent. These cases are a distinctive-appearing rhabdomyosarcoma easily mistaken for variants of chondrosarcoma, osteosarcoma, or even sclerosing epithelioid fibrosarcoma because of their hyalinizing appearance compounded by their typically focal and dot-like desmin expression. These four cases are essentially identical to the three unusual RMSs recently reported by Mentzel and Katenkamp as "sclerosing, pseudovascular rhabdomyosarcoma in adults." Although the focal alveolar architecture and the primitive cytologic appearance of these hyalinizing RMS suggest a relationship with ARMS, the presence of abundant strap cells in one case, the predominant expression of MyoD1 rather than myogenin, and the absence of ARMS-associated fusions genes point more strongly toward a variant of ERMS. However, the late adult age in two cases is unusual for both EMRS and ARMS, suggesting that sclerosing RMS may prove to be a distinct subtype of RMS. Study of additional cases will be necessary to more fully elucidate its place among RMS and its prognostic significance.

Adolescent↗

Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics.

Perineuriomas are rare benign soft tissue tumors having an immunophenotype paralleling the normal perineurial cell [S-100 protein negative and epithelial membrane antigen (EMA) positive]. Because EMA expression in perineuriomas may be focal and/or faint, there is continued interest in the development of new markers of perineurial differentiation. Perineurial cells differ from almost all other mesenchymal cell types by virtue of their formation of tight junctions. In the course of evaluating a group of novel tight junction-associated proteins, we noted high levels of expression of claudin-1 by normal perineurial cells and have systematically extended these observations to perineuriomas. Twelve EMA-positive/S-100-negative perineuriomas were retrieved from our consultation archives and compared with 39 tumors in the differential diagnosis of perineurioma (seven dermatofibrosarcoma protuberans, eight low-grade fibromyxoid sarcomas, three desmoplastic fibroblastomas, seven fibromatoses, nine neurofibromas, and five schwannomas). All cases were immunostained for claudin-1 using standard avidin-biotin technique. Cases were scored as 3+ (>50% positive cells), 2+ (25-50% positive cells), and 1+ (5-24% positive cells). In all cases positive internal controls in the form of epithelium, normal perineurium, or endothelial cells were present. Positive staining for claudin-1 was visualized in a distinctly particulate pattern along the cell membrane. Cytoplasmic staining was infrequent and was not scored as positive. Claudin-1 expression was present in 11 of 12 (92%) perineuriomas studied (seven at 3+, three at 2+, and one at 1+). In all but two cases, the degree of claudin expression was equal to or greater than the corresponding EMA immunostain. Claudin-1 expression was not noted in any cases of dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, desmoplastic fibroblastoma, or fibromatosis. Six of nine cases of neurofibroma contained a significant number of claudin-1-positive cells that were thought to be perineurial in origin, based on the staining of long, delicate cytoplasmic processes. One of four schwannomas contained a subpopulation of perivascular, dendritic, claudin-1-positive cells of presumed perineurial lineage. This is the first study to document expression of claudin-1 in perineurial cells and suggests a role for claudin-1 immunohistochemistry in the diagnosis of perineuriomas. Although claudin-1 should not replace EMA in the diagnosis of perineurioma, we think that it may play a valuable adjunctive role in difficult cases. In particular, claudin-1 is often a more robust marker than EMA in a given perineurioma. Claudin-1 is not expressed within the lesional cells of the mesenchymal tumors that enter into the differential diagnosis of perineurioma.

Biomarkers, Tumor↗

An approach to the diagnosis of flat intraepithelial lesions of the urinary bladder using the World Health Organization/ International Society of Urological Pathology consensus classification system.

The classification of flat urothelial (transitional cell) lesions with atypia has historically varied in its application from institution to institution with no fewer than six major nomenclature systems proposed in the past 25 years. In 1998, the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) published a consensus classification that included the following categories for flat urinary bladder lesions: reactive atypia, atypia of unknown significance, dysplasia (low-grade intraepithelial neoplasia), and carcinoma in situ (high-grade intraepithelial neoplasia). This classification expands the definition traditionally used for urothelial carcinoma in situ, basing its diagnosis primarily on the severity of cytologic changes. In proposing the classification system for flat lesions of the bladder with atypia, it was hoped that consistent use of uniform diagnostic terminology would ultimately aid in a better understanding of the biology of these lesions. In this review, the authors discuss the history of the concept of flat urothelial neoplasia, the rationale and histologic criteria for the WHO/ISUP diagnostic categories, an approach to the diagnosis of flat lesions, and problems and pitfalls associated with their recognition in routine surgical pathology specimens.

Carcinoma in Situ↗