Distinct Immunohistochemical Profile Research Articles

Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis

Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.

Differential pericyte marker expression in craniofacial benign and malignant vascular tumors.

Vascular anomalies and tumors are common in the head, neck, and craniofacial areas and are associated with abnormalities in the angiomatous architecture. However, the etiology and molecular basis for the pathogenesis of most vascular lesions are still unknown. Pericytes are mural cells that surround endothelial cells. Besides angiogenesis and other physiological functions, pericytes play an important role in vascularized tissue repair and as resident mesenchymal stem/progenitor cells. Perivascular cells demonstrate a distinct immunohistochemical profile, including expression of alpha-smooth muscle actin (α-SMA), CD146, CD105, and PDGFRβ, without endothelial differentiation (absence of CD31 and CD34 immunoreactivity). These pericyte markers have been shown to be expressed in soft tissue hemangiomas. However, they have not been fully examined in intraosseous hemangiomas. In this study, we compared mesenchymal stem cell (MSC)expression of CD146 and α-SMA markers inpericytes from hemangiomas from different tissues and malignant vascular tumors. The results demonstrated an increased expression of pericyte markers in perivascular cells of benign hemangiomas, especially intraosseous hemangiomas and a significantly reduced expression of pericyte markers in malignant angiosarcomas. The evidence provides insight into the function of pericytes in vascular tumors and suggests their role in vascular tumor disease types.

Update on Sinonasal Tract Malignancies: Advances in Diagnostic Modalities.

Sinonasal tract malignancies are rare cancers with frequent morphologic overlap. Given the similar histologic profiles seen in many of these entities, they often present a diagnostic challenge to the practicing pathologist. To provide a streamlined algorithm using histologic clues, immunohistochemical profiles, and molecular assays to aid in diagnosis of these lesions. Sources were the World Health Organization Tumor Classification, literature review, and institutional experience. Although many sinonasal tract malignancies show similar histology, distinct immunohistochemical and molecular profiles can help parse out differences, thereby facilitating diagnosis for the pathologist.

Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrPSc Profile

Bovine spongiform encephalopathy (BSE) belongs to the group of transmissible spongiform encephalopathies and is associated with the accumulation of a pathological isoform of the host-encoded glycoprotein, designated prion protein (PrPSc). Classical BSE (C-type) and two atypical BSE forms (L- and H-type) are known, and can be discriminated by biochemical characteristics. The goal of our study was to identify type-specific PrPSc profiles by using Immunohistochemistry. In our study, brain samples from 21 cattle, intracerebrally inoculated with C-, H-, and L-type BSE, were used. In addition, the corresponding samples from three orally C-type BSE infected animals were also included. From all animals, a lesion and PrPSc-profiles of six brain regions were determined. The lesion profile and the neuroanatomical distribution of PrPSc was highly consistent between the groups, but the immunohistochemical analysis revealed a distinct PrPSc profile for the different BSE-types, which included both the topographic and cellular pattern of PrPSc. This qualitative and quantitative analysis of PrPSc affected structures sheds new light into the pathogenesis of the different BSE types. Furthermore, immunohistochemical characterization is supported as an additional diagnostic tool in BSE surveillance programs, especially when only formalin-fixed tissue samples are available.

Papillary renal neoplasm with reverse polarity with a favorable prognosis should be separated from papillary renal cell carcinoma

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly documented renal entity with an easily recognizable morphology, distinct immunohistochemical profiles, and frequent KRAS mutations. The latest practice guidelines regard PRNRP as a subtype of papillary renal cell carcinoma due to the documented chromosomal alterations of 7, 17, and Y. This study included 20 patients with PRNRP and 30 patients with PRCC. Statistically significant differences were observed in size, WHO/ISUP grade, macrophages in the papillae, reverse polarity, CK7, basolateral positivity for Claudin7, GATA3 expression, KRAS mutation, and chromosomal alterations. No adverse events such as perinephric invasion, lymphovascular invasion, sarcomatoid of rhabdoid differentiation, metastasis, or recurrence were found in PRNRP. However, PRCC can cause these adverse events. Basolateral positivity for Claudin7 together with GATA3 expression indicated distal tubule derivation of PRNRP. KRAS mutations were detected in 89% (16/18) of PRNRP. No KRAS mutations were detected in PRCC. Six patients with PRNRP had one chromosomal alteration and the other 12 had no chromosomal alterations. However, only four patients with PRCC showed no chromosomal alterations. Eighteen patients had two or three chromosomal alterations. PRCC can metastasize, recur, and even cause death, whereas PRNRP has a favorable prognosis. We recommend that PRNRP should be separated from PRCC and partial nephrectomy is more suitable for PRNRP.

Gene expression profiles of the original tumors influence the generation of PDX models of lung squamous cell carcinoma

Patient-derived xenograft (PDX) murine models are employed for preclinical research on cancers, including non-small cell lung cancers (NSCLCs). Even though lung squamous cell carcinomas (LUSCs) show the highest engraftment rate among NSCLCs, half of them nevertheless show PDX failure in immunodeficient mice. Here, using immunohistochemistry and RNA sequencing, we evaluated the distinct immunohistochemical and gene expression profiles of resected LUSCs that showed successful engraftment. Among various LUSCs, including the basal, classical, secretory, and primitive subtypes, those in the non-engrafting (NEG) group showed gene expression profiles similar to the pure secretory subtype with positivity for CK7, whereas those in the engrafting (EG) group were similar to the mixed secretory subtype with positivity for p63. Pathway analysis of 295 genes that demonstrated significant differences in expression between NEG and EG tumors revealed that the former had enriched expression of genes related to the immune system, whereas the latter had enriched expression of genes related to the cell cycle and DNA replication. Interestingly, NEG tumors showed higher infiltration of B cells (CD19+) and follicular dendritic cells (CD23+) in lymph follicles than EG tumors. Taken together, these findings suggest that the PDX cancer model of LUSC represents only a certain population of LUSCs and that CD19- and CD23-positive tumor-infiltrating immune cells in the original tumors may negatively influence PDX engraftment in immunodeficient mice.

Association between bone involvement on PET/CT and event free survival (EFS) in follicular lymphoma (FL) grade 3b.

e20068 Background: FL grade 3B (FL3B) is an aggressive subtype of FL with a distinct morphologic, cytogenetic and immunohistochemical profile that is associated with higher mortality compared to other subtypes of FL. FL3B is a rare disease, and data regarding its prognostication beyond grading is lacking. Recent data suggests that spleen and extranodal (EN) involvement on PET/CT predict early clinical failure in FL grades 1-3A[1]. We aimed to determine the incidence of spleen and EN involvement on PET/CT in FL3B, and whether these can predict EFS. Methods: Patients with untreated FL3B diagnosed between 2003-2016, with available pre-treatment PET/CT, were identified using the Mayo Clinic Lymphoma Database and the University of Iowa/Mayo Clinic Lymphoma SPORE database. 27 patients were included in this analysis. All but two patients received treatment with immunochemotherapy. Associations with outcomes were assessed using EFS, defined as disease progression, relapse, transformation, or death. Results: 11/27 (40.7%) of patients had EN involvement on PET/CT. The most common EN site was bone, in 8/27 (29.5%) of patients. Soft tissue involvement was present in 4/27 (14.8%) of patients. Liver, brain, and endometrial involvement were each noted once. 11/27 (40.7%) of patients had spleen involvement on PET/CT. Presence of bone involvement as detected on PET/CT was associated with lower EFS (p = 0.02). EN involvement was associated with a trend toward a lower EFS but statistical significance was not reached likely secondary to low numbers in this cohort. Results in the table are compared to results obtained from our analysis in patients with FL grade 1-3A[1]. Conclusions: Bone involvement on pre-treatment PET/CT in FL3B was associated with early clinical failure in this small cohort of 27 patients. EN involvement at diagnosis may also be associated with poorer outcomes. These findings are similar to our analysis of a large (n = 613) cohort of patients with FL grade 1-3A. These findings may aid in the prognostication of patients with newly diagnosed FL3B, to guide therapy in select higher risk patients. [Table: see text]

Abstract A31: A distinctive genomic and immunohistochemical profile for NOTCH3 and PDGFRB in infantile myofibroma with diagnostic and therapeutic implications

Abstract Infantile myofibromas (IM) are rare benign neoplasms thought to derive from perivascular myoid cells. The prognosis is generally good, although about one-third of cases with multicentric involvement will also have visceral involvement, and the prognosis for these patients is poor. The use of combination cytotoxic chemotherapy (vincristine/dactinomycin and vinblastine/methotrexate) has proven effective in cases of multicentric disease with visceral involvement and in cases in which the disease has progressed and has threatened the life of the patient. The pathologic diagnosis of IM can be challenging, particularly with small biopsies, since IM exist on a morphologic spectrum with myopericytomas, glomangiopericytomas, and glomus tumors, and other spindle cell neoplasms are also on the histologic differential. Most families with autosomal dominant infantile myofibromatosis have germline variants in PDGFRB. In one case of autosomal dominant IM a NOTCH3 variant was identified in the absence of a PDGFRB variant. Most sporadic infantile myofibromas also have identifiable variants in PDGFRB. To date, however, there have been no genetic variants or immunohistochemical stains that are 100% sensitive or specific in diagnosing IM. Nine cases of infantile myofibroma/myofibromatosis were identified from the case archives of Boston Children’s Hospital. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue sections and sequenced using a clinically validated targeted panel of 447 genes for 9 cases. Immunohistochemical stain for activated NOTCH3 was performed. The histopathology of each case was reviewed by two pediatric pathologists. Of the nine IM cases, 7 had one or more sequence variants in PDGFRB. One case had a NOTCH3 sequence variant and one had a NOTCH2 sequence variant. All nine cases (100%) had a distinctive pattern of copy alterations including gains of PDGFRB and NOTCH3. One case failed immunohistochemical staining; of the remaining 8 IM cases, all 8 showed nuclear staining for activated NOTCH3. We describe a distinctive pattern of genomic alterations in infantile myofibromatosis, including a high prevalence (7/9 cases) of alterations in PDGFRB, several of which are known to be activating, and copy number alterations including copy number gains of PDGFRB and NOTCH3 in all 9 cases. The p.N666K, p.D850V (both seen in this study), and p.R561C variants have been shown to result in constitutive activation of PDGFRB, transform cells and induce tumor formation, and render tumor sensitivity to tyrosine kinase inhibitors. In vascular smooth muscle cells, PDGFRB has been shown to be an immediate downstream target of NOTCH3 signaling. The consistent presence of activated NOTCH3, detected by immunohistochemistry in all IM cases, confirms that the genomic changes have functional effect. The NOTCH signaling pathway is the target of inhibitors including gamma-secretase inhibitors; some NOTCH-mutated leukemias have been shown to be sensitive to inhibition, suggesting that these inhibitors may also be useful in NOTCH-mutated myofibromas. Our findings suggest a common pathway of PDGFRB/NOTCH3 activation in infantile myofibromas. Identification of the characteristic genomic alterations or immunohistochemical staining pattern may facilitate a difficult pathologic diagnosis. Furthermore, targeted inhibitors are available for both PDGRFB and NOTCH, and may be of use in patients with visceral or multicentric disease. Citation Format: Selene C. Koo, Calicchio Monica, Benjamin Ferland, Marian H. Harris, Jon C. Aster, Katherine A. Janeway, Alyaa Al-Ibraheemi, Alanna J. Church. A distinctive genomic and immunohistochemical profile for NOTCH3 and PDGFRB in infantile myofibroma with diagnostic and therapeutic implications [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A31.

Mammary analogue secretory carcinoma of salivary glands: diagnostic pitfall with distinct immunohistochemical profile and molecular features.

Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4th edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry.

- Different types of mature B-cell lymphomas, including plasma cell neoplasms, exhibit distinct immunohistochemical profiles, which enable them to be correctly diagnosed. However, except for rare examples of lymphoma-specific immunohistochemistry, such as cyclin D1 in mantle cell lymphoma and annexin A1 in hairy cell leukemia, immunohistochemical profiles of mature B-cell lymphomas overlap and lack specificity. - To systemically review immunohistochemical features associated with commonly encountered mature B-cell lymphomas based on the presence or absence of CD5 and CD10; to review the immunophenotypic profile of plasma cells derived from plasma cell myelomas and B-cell lymphomas; and to review a group of rare, aggressive B-cell lymphomas with antigen expression features of plasma cells. - Published and PubMed-indexed English literature was reviewed. - Although the presence or absence of CD5 and CD10 expression should be included in the initial immunohistochemistry screening panel for mature B-cell lymphomas, appropriate and judicial use of other B-cell antigens is necessary to ensure correct diagnoses. Furthermore, although the status of CD5 and CD10 expression is associated with certain prototypes of B-cell lymphomas, their expression is not specific. Plasma cells from plasma cell neoplasias and B-cell lymphomas exhibit overlapping but relatively distinct immunophenotypes; thus, a panel of immunohistochemical markers (CD19, CD45, CD56, and CD117) can be employed for their proper identification. Lastly, CD138 staining results are almost always positive in a group of aggressive B-cell lymphomas with plasmablastic features, including plasmablastic plasma cell myeloma, plasmablastic lymphoma, and ALK-1+ large B-cell lymphoma.

Distinctive immunohistochemical profile of the penile distal urethra

Distinctive immunohistochemical profile of the penile distal urethra

Angiomyolipoma With Epithelial Cysts.

Angiomyolipoma with epithelial cysts is a rare mesenchymal tumor of the kidney that enters in the differential diagnosis of adult cystic renal neoplasms. These tumors demonstrate a slight female predominance and can present either incidentally or with symptoms, commonly flank pain and hematuria. Unlike conventional angiomyolipoma, this variant is characterized grossly by both solid and cystic areas, and histologically by the presence of single or multiple cysts lined by epithelial cells, a subepithelial "cambium-like" layer of small stromal cells with a prominent capillary vasculature, and a thick exterior wall composed of poorly formed fascicles of smooth muscle and thick-walled dysplastic blood vessels. Tumors show a distinct immunohistochemical profile and are often reactive for melanocytic markers (HMB-45 and Melan-A), as well as estrogen receptor and progesterone receptor. These tumors have an indolent clinical course, with no reports of progression or metastasis in reported cases thus far.

Pericytic mimicry in well-differentiated liposarcoma/atypical lipomatous tumor

Pericytes are modified smooth muscle cells that closely enwrap small blood vessels, regulating and supporting the microvasculature through direct endothelial contact. Pericytes demonstrate a distinct immunohistochemical profile, including expression of smooth muscle actin, CD146, platelet-derived growth factor receptor β, and regulator of G-protein signaling 5. Previously, pericyte-related antigens have been observed to be present among a group of soft tissue tumors with a perivascular growth pattern, including glomus tumor, myopericytoma, and angioleiomyoma. Similarly, malignant tumor cells have been shown to have a pericyte-like immunoprofile when present in a perivascular location, seen in malignant melanoma, glioblastoma, and adenocarcinoma. Here, we examine well-differentiated liposarcoma specimens, which showed some element of perivascular areas with the appearance of smooth muscle (n = 7 tumors). Immunohistochemical staining was performed for pericyte antigens, including smooth muscle actin, CD146, platelet-derived growth factor receptor β, and regulator of G-protein signaling 5. Results showed consistent pericytic marker expression among liposarcoma tumor cells within a perivascular distribution. MDM2 immunohistochemistry and fluorescence in situ hybridization for MDM2 revealed that these perivascular cells were of tumor origin (7/7 tumors), whereas double immunohistochemical detection for CD31/CD146 ruled out an endothelial cell contribution. These findings further support the concept of pericytic mimicry, already established in diverse malignancies, and its presence in well-differentiated liposarcoma. The extent to which pericytic mimicry has prognostic significance in liposarcoma is as yet unknown.

Survivin, cyclin D1, and p21hras in keratocystic odontogenic tumors before and after decompression.

The aim of this study was to investigate survivin, cyclin D1, and p21hras expression in keratocystic odontogenic tumors before and after decompression, as well as in pericoronal follicles. A potential correlation between the expression levels of these proteins was also investigated. We analyzed eighteen keratocystic tumors treated by decompression and subsequent enucleation along with seven pericoronal follicles using immunohistochemistry. Keratocystic tumor samples, both before and after decompression, were positive for each of the investigated proteins. In pericoronal follicles, survivin exhibited cytoplasmic staining in contrast to nuclear staining in keratocystic tumors. Cyclin D1 expression was negative in pericoronal follicles, and p21hras expression was similar in both groups. Survivin showed significantly higher expression after decompression, while cyclin D1 and p21hras remained unchanged (P = 0.039, P = 0.255, P = 0.913, respectively). There was no correlation between these proteins neither before nor after decompression. Within the limits of the study, we can conclude that following decompression, keratocystic odontogenic tumors preserve distinct immunohistochemical profiles of cyclin D1 and p21hras expression, despite substantial reduction in size of the lesions. Significant increase of survivin expression after decompression might be attributed to higher level of epithelial proliferation caused by this procedure.

Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features

We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers.Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC).In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC.BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies.

Canalicular Adenoma—Search for the Cell of Origin: Ultrastructural and Immunohistochemical Analysis of 7 Cases and Review of the Literature

Canalicular adenoma (CA) is a rare, benign epithelial neoplasm of the salivary glands. Historically considered to be a variant of basal cell adenoma, this “monomorphic” adenoma has a distinct clinical, morphologic, and immunohistochemical profile. The putative cell of origin remains a topic of debate. A combination of morphology, immunohistochemistry, and ultrastructural analyses have been employed to determine histogenesis, but the interpretations of these studies have implicated multiple different cell types along the salivary gland duct as the cell of origin. The authors sought to further characterize CA using electron microscopy, immunohistochemistry, and special and immuno-stains on 7 cases. Their morphologic, immunohistochemical, and ultrastructural findings support a cell of origin demonstrating features of both the intercalated duct cells and the striated duct luminal epithelial cells.

Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors

The current World Health Organization classification divides endometrial sarcomas into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma. Recent studies suggest undifferentiated endometrial sarcoma is a heterogeneous group and a subgroup with uniform nuclei is more akin to low-grade endometrial stromal sarcoma in terms of morphologic, immunohistochemical and genetic features. We classified endometrial sarcomas treated at our institution from 1998 to 2011 into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma, the latter being further categorized into a group with either uniform or pleomorphic nuclei. Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome. A total of 40 cases were evaluated comprising 23 low-grade endometrial stromal sarcomas, 10 undifferentiated endometrial sarcomas with nuclear uniformity and 7 undifferentiated endometrial sarcomas with nuclear pleomorphism. Low-grade endometrial stromal sarcomas were more often estrogen and progesterone receptor positive (83%) compared with undifferentiated endometrial sarcoma with nuclear uniformity (10%) or with nuclear pleomorphism (0%) (P<0.001). Positivity for p53 was restricted to undifferentiated endometrial sarcomas with more frequent expression in the group with nuclear pleomorphism (57%) than with nuclear uniformity (10%) (P=0.06). Ki-67 proliferation index in >10% of tumor cells more frequent in undifferentiated endometrial sarcoma than low-grade endometrial stromal sarcoma (P=<0.001). JAZF1 rearrangement was detected in 32% of low-grade endometrial stromal sarcomas and in none of the undifferentiated sarcomas. Rearrangement of PHF1 was found in two patients, one with JAZF1−PHF1 fusion. There were no significant differences in clinical behavior between undifferentiated endometrial sarcoma with nuclear uniformity versus nuclear pleomorphism. In conclusion, we found undifferentiated endometrial sarcoma subtypes and low-grade endometrial stromal sarcoma have distinct immunohistochemical and cytogentic profiles. Our data do not show any difference in clinical behavior between subgroups in undifferentiated sarcomas.

Solitary fibrous tumor of the scalp in a child

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that arise most commonly in the pleura but have been increasingly reported in extrapleural sites. The authors report the case of an SFT of the scalp that manifested as an enlarging scalp mass in a 2-year-old boy. The mass was surgically excised. Histological examination showed it to be composed of fusiform cells of variable cellularity with a central hyalinization zone. Immunohistochemical staining was positive for CD34 and negative for smooth muscle actin, S100 protein, desmin, and h-caldesmon. On 1-year follow-up, there was no recurrence of the mass. This case presented some diagnostic difficulty because of the wide range of possible diagnoses for a pediatric scalp mass; however, the distinct immunohistochemical profile helped to eliminate other more frequent fibrous tumors of the scalp. The behavior of scalp SFTs is usually benign, but their course can be unpredictable, and recognition of these lesions is essential.

The 3-layered Ductal Epithelium in Gynecomastia

Gynecomastia is the most common abnormality in the male breast and has been associated with male breast cancer, but whether there is an etiological role remains unknown. In the present study we conducted an immunohistochemical investigation to further characterize gynecomastia. A total of 46 cases of gynecomastia were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor, HER2, androgen receptor, cytokeratins (CK5, CK14, CK7, and CK8/18), p63, E-cadherin, BRST2, cyclin D1, Bcl-2, p53, p16, p21, and Ki67. In addition, 8 cases of male ductal carcinoma in situ and normal breast tissue obtained from autopsies (n=10) and adjacent to male breast cancer (n=5) were studied. Normal ductal male breast epithelial cells were very often ER and Bcl-2 positive (>69%), and progesterone receptor and androgen receptor expression was also common (>39%). Gynecomastia showed a consistent 3-layered pattern: 1 myoepithelial and 2 epithelial cell layers with a distinctive immunohistochemical staining pattern. The intermediate luminal layer, consisting of vertically oriented cuboidal-to-columnar cells, is hormone receptor positive and expresses Bcl-2 and cyclin D1. The inner luminal layer is composed of smaller cells expressing CK5 and often CK14 but is usually negative for hormone receptors and Bcl-2. Male ductal carcinoma in situ was consistently ER positive and CK5/CK14 negative. In conclusion, for the first time we describe the 3-layered ductal epithelium in gynecomastia, which has a distinctive immunohistochemical profile. These results indicate that different cellular compartments exist in gynecomastia, and therefore gynecomastia does not seem to be an obligate precursor lesion of male breast cancer.

Immunohistochemical expression profile of β-catenin, E-cadherin, P-cadherin, laminin-5γ2 chain, and SMAD4 in colorectal serrated adenocarcinoma

The immunohistochemical expression of cell adhesion molecules in colorectal serrated adenocarcinoma is still unknown. The immunostaining patterns of β-catenin, E-cadherin, P-cadherin, laminin 5γ2, and SMAD4 and their relationship to survival were studied in different tumor areas, namely, tumor center and invasive front, the latter comprising tumor bud and non-tumor bud clusters, as described in a previous study of 66 serrated adenocarcinomas and matched conventional carcinomas. Compared with conventional carcinomas, serrated adenocarcinomas showed significantly reduced nuclear β-catenin, membranous E-cadherin, and nuclear SMAD4 but an increased cytoplasmic expression of laminin-5γ2 at the invasive front that was particularly pronounced in the tumor buds. E-cadherin loss at the invasive front was identified as an independent prognostic factor for a poorer outcome in serrated adenocarcinoma. Serrated adenocarcinoma shows a distinct immunohistochemical profile at the invasive front compared with conventional carcinoma, which may account for its less favorable outcome. The lower frequency of nuclear β-catenin in SAC, especially in right-sided tumors, suggests that molecular mechanisms other than the canonical Wnt/β-catenin pathway may have a role in tumor bud formation.