Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy.

Ewing sarcoma is a highly resistant disease with a <10% chance of survival at 5 years after failure of frontline chemotherapy. This is a case report of an Ewing sarcoma patient with metastatic disease recurrence <2 years after standard chemotherapy/radiation who achieved a durable and sustained complete response after 2 series of treatments with Vigil (GMCSF/bi-shRNA furin DNA autologous tumor immunotherapy) serially manufactured from first and second recurrences with ELISPOT assay correlation. Results support justification of further testing of Vigil with ELISPOT assay as a biomarker to assess level of immune response and correlation with disease control.

Cutaneous Cellular Pseudoglandular Schwannoma: An Unusual Histopathologic Variant.

Cellular schwannoma and pseudoglandular schwannoma are both previously described rare variants of schwannoma. The authors present an unusual case of a cellular spindle cell neoplasm with prominent gland-like structures, having features of both variants. The nature of this lesion was confirmed by histology and immunohistochemistry, with diffuse and strong S100 and membranous collagen type IV staining. The gland-like structures were lined by S100 + cells and contained proteinaceous, mucicarmine-negative material, supporting a degenerative, not true glandular, phenomenon. This is the first case of a cutaneous schwannoma demonstrating both marked cellularity and pseudoglandular formation, which the authors have designated cutaneous cellular pseudoglandular schwannoma. Recognition of this extremely rare variant will help avoid diagnostic confusion and overtreatment of this benign entity.

MYB RNA In Situ Hybridization Facilitates Sensitive and Specific Diagnosis of Adenoid Cystic Carcinoma Regardless of Translocation Status.

Adenoid cystic carcinoma (AdCC) can demonstrate histologic and immunohistochemical (IHC) overlap with a wide range of salivary and nonsalivary tumors, especially in small biopsy specimens. While MYB fluorescence in situ hybridization (FISH) frequently is used to confirm the diagnosis of AdCC, the pathognomonic MYB-NFIB fusion is only present in 40% to 70% of cases. Likewise, although MYB RNA overexpression is seen in the vast majority of AdCC regardless of translocation status, MYB IHC has shown suboptimal specificity for this diagnosis. In this study, we sought to determine whether a novel chromogenic RNA in situ hybridization (ISH) platform could directly detect MYB RNA overexpression and offer a rapid diagnostic adjunct for AdCC. We performed MYB RNA ISH on 84 cases of AdCC as well as 128 other salivary tumors and 108 basaloid and sinonasal carcinomas that mimic AdCC. MYB RNA ISH was 92% sensitive for AdCC, including 97% of cases with MYB rearrangement and 83% without MYB rearrangement by FISH. It was also 89% specific for AdCC overall, with 95% specificity among other salivary tumors and 81% specificity in basaloid and sinonasal carcinomas. In contrast, MYB IHC was 94% sensitive but just 54% specific for AdCC. Overall, MYB RNA ISH provides superior sensitivity for the diagnosis of AdCC compared with MYB FISH and superior specificity compared with MYB IHC. This assay could provide a useful tool for rapidly confirming the diagnosis of AdCC in formalin-fixed, paraffin-embedded specimens.

SS18 Break-Apart Fluorescence In Situ Hybridization is a Practical and Effective Method for Diagnosing Microsecretory Adenocarcinoma of Salivary Glands.

Molecular analysis has allowed for refinement of salivary gland tumor classification and, in some cases, the recognition of entirely new tumor types. Microsecretory adenocarcinoma (MSA) is a salivary gland tumor described in 2019 characterized by microcystic growth, bland cytomorphology, luminal secretions, fibromyxoid stroma, and S100/p63 positivity with negative p40. Most important, MSA is defined by MEF2C-SS18 fusion. While this fusion has, to this point, been detected by next-generation sequencing, this is a technique that is currently inaccessible in most diagnostic laboratories. On the other hand, SS18 break-apart fluorescence in situ hybridization (FISH) is widely available and frequently used as an adjunct for diagnosing synovial sarcoma. It is not known if SS18 break-apart FISH is positive in tumors with MEF2C-SS18, or if it is entirely specific for MSA. Break apart FISH for SS18 was performed on 4 cases of MSA, as well as 8 tissue microarrays (TMAs) containing 423 various salivary gland carcinomas: 26 acinic cell carcinomas, 35 adenocarcinomas not otherwise specified, 96 adenoid cystic carcinomas, 3 basal cell adenocarcinomas, 20 epithelial-myoepithelial carcinomas, 15 hyalinizing clear cell carcinomas, 3 intraductal carcinomas, 12 myoepithelial carcinomas, 117 mucoepidermoid carcinomas, 30 polymorphous adenocarcinomas, 45 salivary duct carcinomas, 19 secretory carcinomas, and 2 undifferentiated carcinomas. SS18 break-apart FISH was also performed on whole slides of 2 tumors from the TMAs. All MSA cases demonstrated classic split patterns on SS18 break-apart FISH. On the TMAs, 374 cases were evaluable by FISH, and 372 cases were clearly negative for SS18 rearrangement. Two cases, both mucoepidermoid carcinomas, had rare split signals below the positivity threshold of 12% on their TMA cores, so FISH was performed on whole sections. On the whole sections both tumors were unequivocally negative for SS18 rearrangement. Taken together, SS18 break-apart FISH was 100% sensitive and 100% specific for a diagnosis of MSA. SS18 break-apart FISH, a diagnostic tool widely available in pathology laboratories, appears to be a highly accurate method for diagnosing MSA of salivary glands. Accordingly, this new tumor type may be molecularly confirmed without needing to resort to highly specialized techniques like next-generation sequencing.

The Decline of Salivary Adenocarcinoma Not Otherwise Specified as a Tumor Entity: Reclassification Using Contemporary Immunohistochemical Profiling and Diagnostic Criteria.

The classification of salivary gland carcinomas has become increasingly specific over the last decade with the definition of new tumor types, documentation of novel molecular and immunohistochemical findings, and development of more refined diagnostic criteria. In this setting, it is unclear how many salivary tumors still cannot be easily categorized-and whether such tumors represent undifferentiated malignancies or include additional definable entities. Relying largely on current classification schemes and contemporary immunohistochemical panels, we reassessed salivary tumors previously diagnosed as adenocarcinoma, not otherwise specified (ACA NOS) from 2 large academic medical centers. Fifty-seven ACA NOS (72%) could be reclassified as more specific entities including 31 salivary duct carcinomas (39%), 7 polymorphous adenocarcinomas (9%), 5 epithelial-myoepithelial carcinomas (6%), 4 myoepithelial carcinomas (5%), 4 secretory carcinomas (5%), 1 acinic cell carcinoma (1%), 1 basal cell adenocarcinoma (1%), 1 intraductal carcinoma (1%), and 1 clear cell carcinoma (1%) as well as 2 metastatic squamous cell carcinomas (3%). Of reclassified cases, 21 (37%) represented variant histologies within these categories. ACA NOS comprised 11% of salivary malignancies before reclassification, but only 4% after reclassification. The remaining 22 ACA NOS demonstrated heterogeneous features, with an association between histologic grade and clinical outcome. In effect, ACA NOS is becoming a bygone entity as modern classification schemes and ancillary techniques now permit more specific typing of a majority of these tumors, potentially facilitating more specific prognostication and treatment. Additional distinctive entities such as mucinous adenocarcinoma may still be definable within the ACA NOS category.

Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.

Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.

Variable Expression of S100 Protein in Sinonasal Malignant Mucosal Melanoma: A Potential Diagnostic Pitfall.

Sinonasal malignant mucosal melanoma (SNM) is a rare, aggressive malignancy. The diagnosis of SNM is often quite challenging due to anatomical limitations, frequent lack of pigmentation, variable histologic appearances, and aberrant differentiation (e.g., positivity for cytokeratin, desmin, or neuroendocrine markers). S100 protein is routinely used as a standard screening marker for SNM, but it may lack optimal sensitivity. Our objective was to study the extent of immunohistochemical expression of S100 protein in SNM, and determine its diagnostic value by comparing it to a newer melanoma marker, SOX10. Twenty-three cases of sinonasal MMM were retrieved from the archival files of the Department of Pathology at UT Southwestern Medical Center. The patients included 14 men and 9 women, and ranged from 36 to 90 years (mean 64.9 years). Sections from blocks of formalin-fixed, paraffin-embedded tissue were used for immunohistochemical analysis with S100 protein and SOX10. The extent and intensity of immunostaining was recorded, and H-score was calculated. For a subset of negative or focally positive cases, S100 protein was repeated at a high-volume reference laboratory. S100 protein immunoexpression was quite variable in the SNM cases, with H-scores ranging from 0 to 300 (mean 123). While 11 of 23 cases exhibited strong and diffuse staining (H-score > 100) as expected for melanoma, 7 were weak and/or focal (H-score 1-100), and 5 were completely S100 protein-negative. For 10 cases, the negative or focal results were confirmed by reference laboratory staining. In contrast, all 23 SNM cases were diffusely and strongly positive for SOX10 (H-scores 210-300, mean 296). Our study demonstrated that S100 protein immunoexpression is extremely variable in SNM. Weak or even absent S100 protein staining is not uncommon in SNM, and should not dissuade pathologists from that diagnosis. Our data demonstrates that S100 protein is insufficiently sensitive to be used as a screening marker for SNM, but that SOX10 is consistently and robustly positive, and should therefore replace S100 protein for that purpose. Indeed, for any high-grade sinonasal tumor, pathologists must have a low threshold for utilizing additional markers to exclude the possibility of SNM.

Pediatric Warthin-like Mucoepidermoid Carcinoma: Report of Two Cases with One Persistent/Recurrent as Conventional Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy. While salivary gland neoplasia is rare in children, MEC is much more likely to occur in the pediatric population than Warthin tumor, a common benign salivary gland neoplasm associated with smoking and older age. The recently-reported Warthin-like variant of MEC bears a striking histologic resemblance to Warthin tumor, representing a potential diagnostic pitfall. Therefore, low-power observation of Warthin-like features in pediatric salivary gland tumors should prompt careful diagnostic consideration of Warthin-like MEC. Two cases of Warthin-like MEC in the parotid glands of teenaged patients were identified in the archives of the Department of Pathology at Children's Medical Center in Dallas, Texas. Surgical material for each case was reviewed and both diagnoses were verified. Fluorescence in situ hybridization (FISH) for CRTC1-MAML2 fusion was performed in both cases. Histologically, neither tumor exhibited the classic bilayer of oncocytic epithelial cells characteristic of Warthin tumor. Instead, the neoplastic epithelial cells exhibited architectural and cytologic atypia, with mucous cells interspersed. CRTC1-MAML2 gene fusions were identified via FISH and confirmed the diagnosis of MEC in both cases. Of note is that the second patient's tumor recurred with features of conventional MEC, indicating the potential for Warthin-like MEC to undergo this morphologic change. The present cases illustrate that Warthin-like MEC, like conventional MEC, may occur in the pediatric population. Pediatric and head and neck pathologists must be aware of this variant's existence and diagnostic criteria to avoid misdiagnosis as benign Warthin tumor.

Low Molecular Weight Cytokeratin Immunostaining for Extrafollicular Reticulum Cells is an Effective Means of Separating Salivary Gland Tumor-Associated Lymphoid Proliferation from True Lymph Node Involvement.

Tumor-associated lymphoid proliferation (TALP) is a well-recognized lymphocytic reaction that is commonly associated with certain salivary gland tumors. A salivary carcinoma with TALP may be confused for true lymph node involvement by that tumor, constituting a potential pitfall in tumor staging that may result in unnecessary therapeutic intervention or erroneous prognostication for patients. True lymph nodes harbor populations of extrafollicular reticulum cells (ERCs), which can be highlighted by low molecular weight cytokeratin immunohistochemistry. We sought to determine whether low molecular weight cytokeratin Cam5.2 immunostaining may be utilized to differentiate true lymph node involvement by salivary gland tumors from TALP. The surgical pathology archives of the University of Texas Southwestern Medical Center was searched for cases of salivary gland neoplasms exhibiting either TALP or true lymph node involvement. Hematoxylin and eosin-stained sections were examined. Cases were classified on the basis of a definitive lymph node capsule and subcapsular sinus, as seen on routine histologic evaluation. Low molecular weight cytokeratin Cam5.2 immunostaining was performed and evaluated on all cases. Twenty-three salivary gland carcinomas with TALP and 16 carcinomas involving a lymph node (14 carcinomas metastatic to regional lymph nodes and 2 carcinomas arising from benign lymph node inclusions) were identified. Numerous Cam5.2-positive ERCs were identified within the nodal tissue of all true lymph nodes involved by carcinoma (16 of 16 cases), while Cam5.2-positive ERCs were completely absent in all cases of salivary gland lesions with TALP (0 of 23 cases) (100% vs. 0%, p < .0001, Fisher's Exact). Utilization of low molecular weight cytokeratin Cam 5.2 immunostaining for ERCs is a highly useful tool for distinguishing true lymph node involvement by salivary gland carcinomas from TALP. This strategy may be useful in identifying genuine nodal metastasis in histologically ambiguous cases, and to avoid erroneously upstaging tumor with TALP as nodal metastasis with the resulting prognostic and therapeutic implications. Moreover, low molecular weight cytokeratin immunostaining may be useful in confirming the rare examples of salivary gland tumors arising from intranodal salivary gland inclusions.

Sclerosing Polycystic "Adenosis" of Salivary Glands: A Neoplasm Characterized by PI3K Pathway Alterations More Correctly Named Sclerosing Polycystic Adenoma.

Sclerosing polycystic adenosis (SPA) is a rare benign salivary gland lesion that usually arises from the parotid gland. SPA was originally interpreted to be a non-neoplastic alteration analogous to fibrocystic changes of the breast, but now there is uncertainty about whether it may represent a neoplasm. SPA often contains intraductal proliferations with an appearance similar to ductal neoplasia of the breast, and one study reported X-chromosome inactivation using polymorphisms of the human androgen receptor (Skalova et al., in AJSP 30:939-944, 2006). We investigated the genetics of SPA through targeted next generation sequencing (NGS). Four cases of SPA were retrieved from the authors' consultation files. A custom, targeted NGS panel including 1425 cancer-related genes was performed on all cases, followed by immunohistochemistry for PTEN. All four cases developed in females, ranging from 40 to 69 years (mean 52.5 years), affecting the parotid (n = 3) and submandibular glands (n = 1). All cases exhibited characteristic histologic features of SPA: well-circumscribed lesions with fibrosis and an admixture of ducts, myoepithelial cells and acinar cells, the latter containing brightly eosinophilic intracytoplasmic granules. Two cases had intraductal apocrine epithelial proliferations. By targeted NGS, loss-of-function mutations in PTEN were revealed in all 4 cases. In addition, 2 of 4 cases harbored PIK3CA mutations and 2 of 4 possessed PIK3R1 alterations; one case lacked both PIK3CA and PIK3R1 mutations. PTEN expression by immunohistochemistry was lost in the ductal and acinar elements but not the myoepithelial cells in all cases. SPA is characterized by genetic alterations in the PI3K pathway, with PTEN mutations seen most frequently. This molecular profile is similar to salivary duct carcinoma and the apocrine variant of intraductal carcinoma (i.e., salivary duct carcinoma-in situ). PI3K pathway alterations were found in cases both with and without intraductal apocrine proliferations, and PTEN immunohistochemistry suggested that the ductal and acinar cells, but not myoepithelial cells, were affected. Taken together, these findings strongly support that SPA is a neoplasm, more correctly named "sclerosing polycystic adenoma." The salivary duct carcinoma-like genetic alterations, coupled with the fact that the surrounding myoepithelial cells appear to be non-neoplastic, suggest a close relationship between SPA and apocrine intraductal carcinoma.

Recurrent RET Gene Rearrangements in Intraductal Carcinomas of Salivary Gland.

Intraductal carcinoma (IC) is the World Health Organization designation for lesions previously called low-grade cribriform cystadenocarcinoma. The relationship of IC to salivary duct carcinoma (SDC) is controversial, but currently these are considered distinct entities. It is hypothesized that IC and SDC should have different genomic signatures that may be identifiable by next-generation sequencing. A total of 23 ICs were identified: 14 pure IC and 9 invasive carcinomas with an intraductal component. Five invasive carcinomas were subjected to next-generation paired-end RNA sequencing. Data analysis was performed using FusionSeq and Mutation detection algorithms (MuTect and VarScan) for variant callers. Gene fusion candidates were validated by fluorescence in situ hybridization and reverse transcription polymerase chain reaction, and mutations by Sanger sequencing. Among the 9 invasive carcinomas, all except 1 were apocrine SDCs with an intraductal component. The remaining case showed typical intercalated duct type IC with invasive adenocarcinoma. The 14 pure ICs had typical intercalated duct features (2 showed hybrid intercalated/apocrine features). RNA sequencing predicted a NCOA4-RET fusion, confirmed by reverse transcription polymerase chain reaction, in the intercalated duct type IC invasive component. Six additional cases of pure IC showed RET rearrangement by fluorescence in situ hybridization (7/15=47%). No apocrine carcinomas showed RET rearrangement. RNA sequencing and Sanger sequencing identified PIK3CA (p.E545K/p.H1047R) and/or HRAS (p.Q61R) hotspot mutations in 6 of 8 (75%) apocrine carcinomas. In conclusion, 2 distinctive types of intraductal lesions are emerging based on molecular analysis. Classic intercalated type ICs commonly harbor fusions involving RET and rarely show widespread invasion. Apocrine intraductal lesions are typically associated with widespread invasion with no pure examples and show similar PIK3CA and HRAS mutations to SDC.

Hodgkin's lymphoma associated with plasma cell neoplasia: cytological features and review of the literature.

Hodgkin's lymphoma (HL) associated with plasma cell neoplasia is extremely rare. Here, we report one case diagnosed by fine-needle aspiration biopsy (FNAB) and review the clinical features of 15 previously reported cases. Our specimen was obtained by FNAB of an enlarged right inguinal lymph node. Air-dried Diff-Quik (DQ)-stained slides and alcohol-fixed slides stained with hematoxylin-eosin (H&E) and Papanicolaou stains were reviewed. The specimen was cellular, consisting of lymphocytes and plasma cells. Flow cytometric analysis revealed a monoclonal (M) plasma-cell population. Admixed large atypical mono- and binucleated cells immunoreactive for CD30 were noted also. A diagnosis of plasma-cell neoplasm associated with classic HL was confirmed histologically after surgical removal of the lymph node. The diagnosis of both HL and plasma-cell neoplasia in the same patient is exceedingly rare. Adding another case to the 15 previously reported cases was unique because our case was diagnosed through FNAB.

"Parapharyngeal space" tumors: a cytopathological study of 24 cases on fine-needle aspiration.

The parapharyngeal space (PPS) is a well-defined anatomic zone of loose connective tissue lying deep to the tonsil and lateral to the pharynx. Neoplasms arising within the PPS are rare. We retrospectively reviewed 24 PPS fine-needle aspirations (FNAs) performed at The Johns Hopkins Hospital over the past 16 years (1987-2002). Patients presented with neck pain, dysphagia, and/or intraoral swelling of varying duration. Radiographic imaging disclosed PPS masses, varying in size from 2.5 to 8 cm. The most common clinicoradiographic suspicion was a nerve sheath tumor. Six cases had FNA performed using a 23-gauge needle via a transoral approach in the outpatient suite whereas the remainder were aspirated via a 22-gauge Franseen needle under CT guidance. Six of 24 cases (25%) were nondiagnostic due to lack of adequate cellular material. Of the 18 cases considered diagnostic, there were nine (50%) pleomorphic adenomas (PAs); three (17%) squamous-cell carcinomas (SCC); and one each of oncocytoma, adenocarcinoma, not otherwise specified (NOS), adenoid cystic carcinoma, lipoma, neurofibroma, and non-Hodgkin lymphoma, together comprising the remaining 33%. Four of the six cases deemed nondiagnostic (consisting predominantly of blood) on subsequent tissue follow-up revealed paraganglioma (two cases), SCC (one case), and schwannoma (one case). PPS is an uncommon target of an FNA procedure. PPS masses represent a heterogeneous group of neoplasms of which PA appears most common, representing 50% of our diagnostic cases. The rate of nondiagnostic FNA samples is moderately high due to excessive bleeding encountered in this location and other technical problems relating to adequately targeting the lesion in close vicinity of major neck vessels.

Can basal cells be seen in adenocarcinoma of the prostate?: an immunohistochemical study using high molecular weight cytokeratin (clone 34betaE12) antibody.

Rare reports describe high molecular weight cytokeratin (clone 34betaE12) antibody cross-reactivity in scattered prostate carcinoma (PCa) cells, yet most often not in a true basal cell distribution. There are no data specifically describing 34betaE12 reactivity in basal cells in PCa. From August 10, 1995 to May 1, 2000, a total of 3198 consult prostate needle biopsies with PCa and a 34betaE12 immunoperoxidase stain were reviewed at our institution. Thirty-six cases (1.1%), which on hematoxylin and eosin stain were unequivocal cancer, had at least focal 34betaE12 positivity in a basal cell distribution. Twenty-five had original diagnostic slides for review. All cancers were Gleason score 6. The mean number of cancer glands per case was 36.9 (10-108) with an average of 39% of glands (1-100%) showing 34betaE12 reactivity. Twenty-one cases had patchy staining in a basal cell distribution with one other case showing continuous staining. An additional case showed mainly tumor cell reactivity with rare basal cell staining. The final two cases showed a zonal staining pattern with small glands toward one side of the lesion showing basal cells [one with high grade prostatic intraepithelial neoplasia (HGPIN); one without HGPIN]. HGPIN was present in 16 of 25 (64%) cases adjacent to PCa. The mean number of HGPIN glands was 1.36 (1-6). In cases with HGPIN the mean ratio of cancer to HGPIN glands was 6.8 (0.5-13.0). In 12 cases in which the lesion was still present on deeper sectioning, we were able to confirm in nine cases the presence of basal cells using antibodies to p63, another marker for prostatic basal cells. Four of the 25 men underwent radical prostatectomy; all showed Gleason score 6 PCa. Three radical prostatectomies demonstrated 34betaE12 reactivity: two with patchy staining in a basal cell distribution and one with mainly tumor cell staining. Adjacent HGPIN was present in all three radical prostatectomy specimens. Rare lesions with the appearance of PCa show 34betaE12 staining in a basal cell distribution either from retention of basal cells by early invasive cancer or from HGPIN outpouching. The lack of adjacent HGPIN in some cases and the large ratio of small atypical glands to HGPIN glands argue against HGPIN outpouching as the sole explanation. In cases with adjacent HGPIN a comparison of the proximity and number of the small, atypical, infiltrative appearing glands to HGPIN is helpful. The diagnosis of PCa in the face of positive 34betaE12 basal cell staining should be made with extreme caution, only in the face of unequivocal cancer on the hematoxylin and eosin stain.

Xp11.2 translocation renal carcinoma with placental metastasis: a case report.

Renal cell carcinomas with sporadic Xp11.2 translocations are uncommon malignancies in children and young adults associated with several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Placental metastases are extremely rare, with only a handful of cases reported. This study reports the case of a 20-year-old woman with an Xp11.2 translocation renal carcinoma that metastasized to the placenta. This is the first reported case of a renal cell carcinoma metastatic to the placenta and highlights the aggressive behavior of Xp11 translocation renal cell carcinomas.

Primary renal carcinoid tumors: clinicopathologic features of 9 cases with emphasis on novel immunohistochemical findings.

Primary renal carcinoid tumors are rare neoplasms. Because of the rarity of these neoplasms, clinicopathologic and immunohistochemical characteristics have not been fully characterized. Immunohistochemistry for renal cell lineage transcription factors, such as paired box gene 2 and paired box gene 8, has not been studied in renal carcinoid tumors and may be useful in demonstrating nephrogenic differentiation. We studied the clinical, morphological, and immunohistochemical features in 9 primary renal carcinoid tumors from multiple institutions with particular emphasis on immunohistochemical findings, in particular, expression of paired box gene 2 and paired box gene 8. All 9 cases expressed at least 1 neuroendocrine marker (CD56, synaptophysin, chromogranin). The renal-associated (paired box gene 2/paired box gene 8), gastrointestinal (caudal-related homeobox-2), and pulmonary/thyroid (thyroid transcription factor-1) transcription factors were not expressed in renal carcinoids (0/9). Of interest, CD99 was expressed in 8 of 9 cases, with the one negative case representing an atypical carcinoid. Perinephric extension and nodal and distant metastases are common. The absence of expression of paired box gene 2 and paired box gene 8, although not conclusive, supports the theory that these are derived from nonnephrogenic elements. CD99 was expressed in almost all cases (8/9); recognition of this could prevent misdiagnosis of a renal primitive neuroectodermal tumor.

The utility of C4d, C9, and troponin T immunohistochemistry in acute myocardial infarction.

CONTEXT: Full activation and involvement of the complement pathway follows acute myocardial infarction. Complement fragment C4d is a stable, covalently bound marker of complement activation. Troponin T is specific for cardiomyocytes. OBJECTIVES: To determine the specificity of C4d, C9, and troponin T immunoreactivity in necrotic myocytes and to establish whether they can be used to delineate acute myocardial infarction. DESIGN: Twenty-six autopsy cases with a total of 54 myocardium areas of infarction were reviewed retrospectively. Immunohistochemistry for C4d, C9, and troponin T was used on paraffin sections of formalin-fixed tissue. Controls consisted of 5 cases without evidence of infarction, and histologically normal myocardium functioned as an internal control. RESULTS: C4d and C9 antibodies reacted strongly and diffusely with necrotic myocytes in all samples of infarctions for up to 2 days (19 of 19; 100%). Adjacent histologically normal myocytes were nonreactive, resulting in a clear delineation between damaged and viable myocardium. Reactivity declined with increased duration and was absent in scars. Troponin T showed loss of staining in preinflammatory lesions (8 of 13; 62%); however, nonspecific patchy loss of staining was present in negative controls and in viable myocardium. Immunostains provided new diagnoses in 2 cases, including evidence of reinfarction and a newly diagnosed acute myocardial infarction. CONCLUSIONS: C4d and C9 have comparable reactivity and specificity for necrotic myocytes. C4d and C9 staining of necrotic myocytes is apparent before the influx of inflammatory cells, demonstrating utility in early myocardial infarction. Patchy loss of Troponin T in some cases of histologically normal myocardium limited its usefulness as a sole marker of infarction.