Solid Pattern Yolk Sac Tumor: A Morphologic and Immunohistochemical Study of 52 Cases.
Am J Surg Pathol. 2012 Jan 17;
Authors: Kao CS, Idrees MT, Young RH, Ulbright TM
Abstract
Yolk sac tumors may exhibit numerous patterns. One that has received little attention overall, yet is not uncommon, is a solid pattern, which is especially prone to misinterpretation, usually as seminoma, in biopsy specimens from metastatic or mediastinal sites. This distinction is of critical importance as the 2 tumors are treated differently. To determine features useful in the diagnosis of solid yolk sac tumor we reviewed 52 germ cell tumors (28 testicular primaries, 21 metastases from the testis, and 3 mediastinal primaries) that had a yolk sac tumor component with foci of solid growth, defined as a sheet-like arrangement of tumor cells occupying >2 mm and with no or only rare microcysts. Solid yolk sac tumor was almost always associated with other patterns, most commonly microcystic/reticular (75%), glandular (35%), and myxoid (25%). The solid foci consisted of sheets of cells with usually abundant cytoplasm that was mostly (85%) pale to clear and frequently had intercellular basement membrane deposits (75%), rare microcysts (67%), significant nuclear pleomorphism (65%), and hyaline globules (65%). In 2 cases (4%), the cells were small with scant cytoplasm (blastema-like variant). A myxoid background (39%), lymphocytic infiltrate (17%), and an appliqué pattern (8%) were sometimes observed. On immunostaining, AE1/AE3 cytokeratin and glypican 3 provided the most intense and diffuse reactivity for solid yolk sac tumor, whereas α-fetoprotein was negative in 38%. CD117 stained 59%, whereas only rare cells in 1 case (3%) were weakly reactive for podoplanin; OCT3/4 was uniformly negative. We conclude that solid yolk sac tumor can generally be recognized by careful morphologic evaluation, especially its association with other yolk sac tumor patterns, the presence of intercellular band-like deposits of basement membrane, occasional microcysts, nuclear pleomorphism, intracellular hyaline globules, and usual absence of lymphocytes. In difficult cases a concise immunohistochemical panel consisting of AE1/AE3, glypican 3, and OCT3/4 distinguishes solid yolk sac tumor from other neoplasms. α-fetoprotein stains are commonly negative or weak and focal in solid yolk sac tumor and cannot be solely relied on for diagnosis. Common CD117 positivity in solid pattern yolk sac tumors makes it an unreliable discriminator between yolk sac tumor and seminoma.
PMID: 22261704 [PubMed - as supplied by publisher]
Infectious granulomatous prostatitis is uncommon, and most cases of granulomatous prostatitis are classified as nonspecific granulomatous prostatitis. From 2007 to 2009, 5 patients experienced poor wound healing after radical prostatectomy for prostate cancer at a specialist cancer center. Mycobacterium abscessus was cultured from the debridement specimens, and acid-fast-positive bacilli were identified histologically within the prostates. All 180 radical prostatectomy specimens from May 2007 to June 2009 were reviewed, and 7 additional cases with morphologies suspicious of M. abscessus granulomatous prostatitis (MAGP) were identified. The characteristic morphologic feature of MAGP was suppurative necrotizing granulomatous inflammation extensively (10% to 80% of the gland; mean, 39%) involving the prostate. The centers of MAGP were large areas of neutrophilic abscess and necrotic debris, which were surrounded by histiocytes, lymphocytes, plasma cells, scattered multinucleated giant cells, and eosinophils. In the adjacent areas, there was a lobular extension of mixed inflammatory infiltrates into dilated and ruptured ducts. Involvement of extraprostatic soft tissue and seminal vesicles/vas deferens was found in 9 and 4 cases, respectively. Acid-fast-positive bacilli were identified in 5 radical prostatectomies. Eleven patients had fresh tissue specimens stored at -150°C, and M. abscessus was cultured from 8 prostates. Random amplified polymorphic DNA-polymerase chain reaction showed the same clone for all isolates. After prostatectomy, 8 patients experienced prolonged wound healing, with urethrorectal fistula formation in 1 patient and a pelvic abscess in another. It is critical for pathologists to recognize MAGP and to distinguish it from the more common nonspecific granulomatous prostatitis and other granulomatous lesions within the prostate.
PMID: 22261705 [PubMed - as supplied by publisher]
Prognostic Significance in Substaging of T1 Urinary Bladder Urothelial Carcinoma on Transurethral Resection.
Am J Surg Pathol. 2012 Jan 17;
Authors: Chang WC, Chang YH, Pan CC
Abstract
T1 papillary urothelial carcinomas of the urinary bladder run a variable clinical course, and an effective substaging system has not been defined yet. This study was conducted to devise an easy-to-use substaging method and to validate its prognostic value in T1 cancer on transurethral resection specimens. A total of 103 cases of T1 low-grade papillary urothelial carcinoma and 406 cases of T1 high-grade papillary urothelial carcinoma from a series of 1515 non-muscle-invasive bladder tumors treated by transurethral resection were studied. Substaging was performed using 0.5, 1.0, and 1.5 mm as thresholds to distinguish extensive from focal invasion. Correlations to recurrence, progression, cancer-specific mortality, and all-cause mortality were explored and compared with Ta tumors. All lamina propria invasions in low-grade papillary urothelial carcinomas were confined to 1.0 mm. The proportions of T1 high-grade papillary urothelial carcinoma invading beyond 0.5, 1.0 (T1>1 mm), and 1.5 mm were 53%, 32%, and 27%, respectively. No prognostic differences were found between Ta and T1 low-grade papillary urothelial carcinomas. T1>1 mm high-grade papillary urothelial carcinomas were associated with significantly greater risks for recurrence, progression, cancer-specific mortality, and all-cause mortality compared with T1≤1 mm and Ta tumors. Comparable statistical results could be obtained using 0.5 and 1.5 mm as cutoff points, but we recommend using 1.0 mm for practical consideration. Taking all non-muscle-invasive urothelial neoplasms of the bladder into consideration, 5 prognostically distinct categories can be established: (1) papillary urothelial neoplasms of low malignant potential; (2) low-grade papillary urothelial carcinoma Ta/1; (3) high-grade papillary urothelial carcinoma Ta; (4) high-grade papillary urothelial carcinoma T1≤1 mm; and (5) high-grade papillary urothelial carcinoma T1>1 mm. Our study demonstrates that the substaging of T1 bladder cancer is feasible, based on the evaluation of transurethral resection specimens, and can provide more precise prognostic information to identify a subset of patients with a more unfavorable prognosis.
PMID: 22261706 [PubMed - as supplied by publisher]
Angioleiomyomas of the Dura: Rare Entities That Lack KRIT1 Mutations.
Am J Surg Pathol. 2012 Jan 17;
Authors: Conner TM, Waziri A, Kleinschmidt-Demasters BK
Abstract
Angioleiomyomas (ALMs) are cutaneous and soft tissue lesions usually seen in the lower extremities of middle-aged women. The lesions are nodular, mulberry like, and composed of vessels of varying size with abundant intervening smooth muscle; an arterial component is absent. Intracranial examples are exceedingly rare, with <10 cases reported to date, and are usually dural in location. We report the case of 2 young men with dural ALMs: one infratentorial and located near the incisura and the second falcine, posterior to the splenium. Both patients came from the same medium-size community in southern Colorado with a known high incidence of a Hispanic population at risk for familial cavernous cerebral hemangiomas (fCCMs). Both presented within a month of each other with greater than 8-year histories of headaches; preoperative and intraoperative diagnoses were cerebral cavernous malformation (CCM) or vascular meningioma. Histologically, both had discrete lesions composed of large cavernous channels lined by a single layer of cytologically bland endothelium and surrounded by mature, smooth muscle of varying thickness that was orderly near the lumen, more disorganized in intervening areas, and immunoreactive for smooth muscle actin (SMA), muscle-specific actin, and vimentin but not for desmin. Concentric whorls of SMA/CD34 cells were a distinctive feature. We posited that there might be a relationship between dural ALMs and CCMs and undertook polymerase chain reaction-based mutational analysis for the single common mutation seen in Hispanics with familial cavernous cerebral hemangiomas, that is, c.1363C>T KRIT1. Testing proved negative, despite the fact that 1 patient was of strong Hispanic heritage. We concluded that dural ALMs are easily clinically mistaken for CCMs or meningiomas but are not of similar histopathogenesis.
PMID: 22261708 [PubMed - as supplied by publisher]
Divergent Expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in Dysplasia and Intramucosal Adenocarcinomas With Intestinal and Foveolar Morphology: Is This Evidence of Distinct Gastric and Intestinal Pathways to Carcinogenesis in Barrett Esophagus?
Am J Surg Pathol. 2012 Jan 17;
Authors: Khor TS, Alfaro EE, Ooi EM, Li Y, Srivastava A, Fujita H, Park Y, Kumarasinghe MP, Lauwers GY
Abstract
Dysplasia in Barrett esophagus has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a tumor suppressor role for CDX-2 in the metaplasia-dysplasia-carcinoma sequence. The phenotypic stability and role of CDX-2 in the neoplastic progression of different types of dysplasias have not been evaluated. Thirty-eight endoscopic mucosal resections with dysplasia and/or intramucosal carcinoma (IMC) arising in Barrett esophagus were evaluated for the expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2. The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had IMC and dysplasia, 8 had IMC only, and 7 had dysplasia only. Among dysplastic lesions, 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with dysplasia and adjacent IMC showed an identical immunophenotype of dysplasia and IMC comprising 16 gastric, 3 intestinal, and 1 mixed immunophenotype. Three cases showed discordance of dysplasia and IMC immunophenotype. These findings suggest that most Barrett-related IMC cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of carcinogenesis. CDX-2 showed gradual downregulation of expression during progression in adenomatous dysplasia but not in foveolar or hybrid dysplasia, supporting a tumor suppressor role, at least in the intestinal pathway. CDX-2 was also found to be expressed to a greater degree in intestinal metaplasia compared with nonintestinalized columnar metaplasia. Consistent with CDX-2 as a tumor suppressor, this suggests that nonintestinalized columnar metaplasia may be an unstable intermediate state at risk for neoplastic progression.
PMID: 22261707 [PubMed - as supplied by publisher]
HPV-associated Neuroendocrine Carcinoma of the Oropharynx: A Rare New Entity With Potentially Aggressive Clinical Behavior.
Am J Surg Pathol. 2012 Jan 31;
Authors: Kraft S, Faquin WC, Krane JF
Abstract
High-grade neuroendocrine carcinoma of the head and neck is an aggressive neoplasm which rarely arises in the oropharynx. Here we report a series of 8 oropharyngeal neuroendocrine carcinomas associated with both human papillomavirus (HPV) infection and tobacco exposure. The tumor occurred predominantly in male patients (6 of at a mean age of 59 years. Histologically, these cases were all classified as poorly differentiated neuroendocrine carcinoma (small cell carcinoma) with high mitotic activity [mean 53.3 mitoses per 10 HPF], necrosis, high nuclear-to-cytoplasmic ratio, and nuclear molding. One case also exhibited a moderately differentiated component, and one other case had a component of squamous cell carcinoma with basaloid features. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin and/or chromogranin A in all cases. P63 staining was negative, except in 1 case. Seven of the 8 cases showed strong and diffuse p16 expression, a surrogate marker for high-risk HPV infection. HPV infection was confirmed in 6 of these 7 cases by HPV in situ hybridization and/or polymerase chain reaction analysis. HPV subtypes 16, 18, and 33 were identified in 1 case each by polymerase chain reaction testing. Six of the 7 patients for whom clinical history was available presented with advanced disease (4 with regional lymph node metastases, 1 with distant metastases, and 1 with distant and locoregional metastases). Disease recurred in 5 of the 6 patients with available clinical follow-up, with 3 developing distant metastases to brain, bones, lung, pleura, adrenal glands, and pancreas. These 3 cases were all from the HPV-positive group. In summary, neuroendocrine carcinoma of the oropharynx represents a rare novel HPV-associated entity with high-grade histologic features and aggressive clinical behavior.
PMID: 22301491 [PubMed - as supplied by publisher]
Use of Mismatch Repair Immunohistochemistry and Microsatellite Instability Testing: Exploring Canadian Practices.
Am J Surg Pathol. 2012 Jan 31;
Authors: Kalloger SE, Allo G, Mulligan AM, Pollett A, Aronson M, Gallinger S, Torlakovic EE, Clarke BA
Abstract
BACKGROUND:: The mismatch repair (MMR) status of tumors is being increasingly recognized as a prognostic, predictive, and possible germline predisposition/Lynch syndrome (LS) biomarker in colorectal cancer and other cancer types, particularly in endometrial cancer. Current methods (clinical history and tumor morphology) to predict MMR deficiency (dMMR) are suboptimal, and implementation of reflex laboratory testing of appropriate tumors has been recommended, a strategy requiring test standardization and clinical coordination. METHODS:: Two web-based questionnaires were administered, a general and a specialist laboratory questionnaire, to establish the availability of such tests, requisite clinical/pathology integration, current mode of test initiation, reporting and recommendation practices, and education and attitudes among pathologists. Technical aspects were reviewed on the basis of specialist laboratory practice. RESULTS:: Of 76 respondents, 21.5% were unaware or were uncertain whether they had access to MMR immunohistochemistry. Although 78.9% of respondents had access to such testing, an integrated approach to the identification of patients with LS is lacking, being limited to just 9 centers. The majority (70%) of testing is clinician initiated, with variable implementation of reflex testing and divergent practices in recommendation to test. Standardized reporting is lacking in many centers. Education on MMR in endometrial cancer is poor compared with that in colorectal cancer (P<0.0001). INTERPRETATION:: This multicenter questionnaire highlights heterogenous practices in dMMR testing and LS identification, both in clinical terms and with regard to technical aspects of testing. An integrated multidisciplinary approach is lacking, and there is a need to educate physicians and resolve ethical issues. A Canadian consensus statement and national guidelines on dMMR testing are urgently needed, requiring input from pathologists, clinicians, and genetic counselors.
PMID: 22301492 [PubMed - as supplied by publisher]
The vast majority of malignant urachal epithelial tumors have a glandular morphology (ie, adenocarcinoma), to which our principal understanding of urachal carcinoma and its prevailing set of diagnostic criteria are largely ascribed. The 2004 World Health Organization classification of genitourinary tumors recognizes other rarer histologic types of urachal carcinomas such as urothelial, squamous cell, and other carcinomas. However, the clinicopathologic data for these nonglandular groups of urachal carcinomas are very limited, being detailed only in sporadic case reports. Some of the criteria recommended for pathologic confirmation of urachal carcinomas were formulated almost exclusively for urachal adenocarcinoma and may not be relevant or applicable for nonglandular tumors. Here, we present 7 examples of pure (5) and mixed predominant (2) nonglandular urachal carcinomas. Patients were 45 to 85 years of age (mean, 64.1) with a male predominance (male-to-female ratio=6:1). Six tumors were related to the bladder [dome (3) or dome/supravesical (3)] and 1 was entirely supravesical. Histologically, 5 were urothelial carcinomas, of pure or mixed histology, all were high grade and invasive, and 2 were small cell carcinomas. Two urothelial carcinomas had focal (<5%) glandular differentiation and signet ring cell change, and 1 had admixed focal malignant squamous cells and high-grade dedifferentiated components. Four of 5 urachal urothelial carcinomas exhibited solid and partly cavitary or luminal growth with papillary structures and a variable amount of necrosis within the cavity. The 2 small cell carcinomas were pure, had classic undifferentiated neuroendocrine histology, were situated at the bladder dome, and were partly cavitary filled with necrotic debris. Urachal remnant was identified in 6 tumors mainly with dysplastic transitional cells in the urachal canal or rudimentary nests and tubules. All 6 bladder-related urachal tumors exhibited reverse invasive front from the surface, including 2 tumors that ulcerated the bladder mucosa. One tumor had concomitant in situ and noninvasive high-grade papillary urothelial carcinomas in the main bladder lumen. Sheldon stages at presentation were IIIA (2), IVA (3), and IVB (2). Follow-up in all 7 cases (<1 to 60 mo; median, 12.5 mo) showed that 6 patients had died of disease, including the 2 patients with small cell carcinoma. In conclusion, nonglandular urachal carcinoma may occur with pure histology or admixed with high-grade dedifferentiated morphologies and a minor adenocarcinoma component. These tumors may arise as deep-seated bladder-related or completely supravesical tumors along the urachal tract and may exhibit reverse invasive spread toward the bladder surface. Cavitary or luminal growth may occur that could be attributed to the intraurachal neoplastic proliferation. Urachal urothelial carcinomas in particular may contain papillary structures within the tumor and urachal cavity. Concomitant primary urothelial carcinoma outside of the urachus and tumor extension to bladder mucosa may occur, which should not negate diagnosis of an urachal primary. Behavior appears poor, as most tumors present with higher stage.
PMID: 22301493 [PubMed - as supplied by publisher]
The response of colorectal adenocarcinoma liver metastases to perioperative chemotherapy can be assessed histologically in partial hepatectomy specimens. Necrosis in this scenario may represent a lack of treatment effect or a therapeutic response to chemotherapy. This study sought to validate the histologic classification of necrosis into 2 types: usual necrosis (UN) representing an absence of treatment effect, and infarct-like necrosis (ILN) representing a therapeutic response to chemotherapy. Tumor regression grade (TRG) is a previously described prognosticating method that estimates tumor replacement by fibrosis. We incorporated ILN into a modified TRG (mTRG) and compared its performance as a prognostic factor against TRG. A retrospective clinical and histologic review was undertaken of all partial hepatectomies performed for colorectal liver metastases at our center between 2004 and 2010. Clinicopathologic features were compared between the 2 types of necrosis, including survival stratified by TRG and mTRG. A total of 109 cases were reviewed, with 46 patients receiving perioperative chemotherapy. ILN was identified in 12 cases, and all of these cases were associated with perioperative chemotherapy. ILN was significantly associated with perioperative treatment with bevacizumab. In patients receiving perioperative chemotherapy, those with ILN had superior disease-free survival compared with those with UN (P=0.047). mTRG1 to 2 scores were associated with significantly better survival compared with mTRG3 to 5 scores. In contrast, use of TRG did not demonstrate a significant difference in disease-free and overall survival. ILN represents a form of treatment effect and should be distinguished from UN. A modified grading system that incorporates ILN may enhance the prognostic utility of TRG.
PMID: 22301494 [PubMed - as supplied by publisher]
Gamma Heavy-chain Disease: Defining the Spectrum of Associated Lymphoproliferative Disorders Through Analysis of 13 Cases.
Am J Surg Pathol. 2012 Jan 31;
Authors: Bieliauskas S, Tubbs RR, Bacon CM, Eshoa C, Foucar K, Gibson SE, Kroft SH, Sohani AR, Swerdlow SH, Cook JR
Abstract
Gamma heavy-chain disease (gHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated immunoglobulin gamma heavy-chain protein that lacks associated light chains. There is scant information in the literature regarding the morphologic findings in this rare disorder, but cases have often been reported to resemble lymphoplasmacytic lymphoma (LPL). To clarify the spectrum of lymphoproliferative disorders that may be associated with gHCD, this study reports the clinical, morphologic, and phenotypic findings in 13 cases of gHCD involving lymph nodes (n=7), spleen (n=2), bone marrow (n=8), or other extranodal tissue biopsies (n=3). Clinically, patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%). Histologically, 8 cases (61%) contained a morphologically similar neoplasm of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that was difficult to classify with certainty, whereas the remaining 5 cases (39%) showed the typical features of one of several other well-defined entities in the 2008 WHO classification. This report demonstrates that gHCD is associated with a variety of underlying lymphoproliferative disorders but most often shows features that overlap with cases previously reported as “vaguely nodular, polymorphous” LPL. These findings also provide practical guidance for the routine evaluation of small B-cell neoplasms with plasmacytic differentiation that could represent a heavy-chain disease and give suggestions for an improved approach to the WHO classification of gHCD.
PMID: 22301495 [PubMed - as supplied by publisher]
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at a mean age of 59 years. Histologically, these cases were all classified as poorly differentiated neuroendocrine carcinoma (small cell carcinoma) with high mitotic activity [mean 53.3 mitoses per 10 HPF], necrosis, high nuclear-to-cytoplasmic ratio, and nuclear molding. One case also exhibited a moderately differentiated component, and one other case had a component of squamous cell carcinoma with basaloid features. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin and/or chromogranin A in all cases. P63 staining was negative, except in 1 case. Seven of the 8 cases showed strong and diffuse p16 expression, a surrogate marker for high-risk HPV infection. HPV infection was confirmed in 6 of these 7 cases by HPV in situ hybridization and/or polymerase chain reaction analysis. HPV subtypes 16, 18, and 33 were identified in 1 case each by polymerase chain reaction testing. Six of the 7 patients for whom clinical history was available presented with advanced disease (4 with regional lymph node metastases, 1 with distant metastases, and 1 with distant and locoregional metastases). Disease recurred in 5 of the 6 patients with available clinical follow-up, with 3 developing distant metastases to brain, bones, lung, pleura, adrenal glands, and pancreas. These 3 cases were all from the HPV-positive group. In summary, neuroendocrine carcinoma of the oropharynx represents a rare novel HPV-associated entity with high-grade histologic features and aggressive clinical behavior.