High Molecular Weight Keratin Research Articles

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-08.

Clinicopathological and molecular features of renal cell carcinomas with haemangioblastoma-like features distinct from clear cell renal cell carcinoma.

Haemangioblastomas arise in the central nervous system. Rarely, haemangioblastomas may develop in extra-neural sites, such as the kidneys. A few reported cases of renal cell carcinomas (RCCs) with haemangioblastoma-like features have exhibited both clear cell renal cell carcinoma (CCRCC)- and haemangioblastoma-like components. The clinicopathological and molecular characteristics of RCCs with haemangioblastoma-like features were analysed, focusing on VHL alterations, in comparison with CCRCCs partially resembling haemangioblastoma. Four RCCs with haemangioblastoma-like features and five CCRCCs partially resembling haemangioblastoma were included. The RCCs with haemangioblastoma-like features were indolent and lacked adverse prognostic factors. All RCCs with haemangioblastoma-like features had a well-circumscribed appearance and a thick fibromuscular capsule, with fibromuscular bundles extending into the tumour to varying degrees in the three tumours. Each RCC with haemangioblastoma-like features exhibited CCRCC-like areas with indistinct tubular structures and foci of haemangioblastoma-like areas, in which vessels and short spindle cells overwhelmed tumour cells. Whereas haemangioblastoma-like areas in the CCRCCs partially resembling haemangioblastoma exhibited sparse vessels and spindle cells and distinct clear cells. The RCCs with haemangioblastoma-like features exhibited a unique immunohistochemical profile, with positive staining for inhibin-α, S100, carbonic-anhydrase-9, keratin7, and high molecular weight keratin and negative staining for (alpha-methylacyl-CoA racemase) AMACR. RCC with haemangioblastoma-like features did not display any VHL alterations, including VHL mutation, 3p LOH, and methylation of the VHL promoter region, and the two tumours harboured a likely oncogenic missense variant of MTOR (c.7280T>G). The histopathological, immunohistochemical, and molecular findings suggest that RCC with haemangioblastoma-like features is a distinct entity from CCRCC.

An in vitro analysis of the hemostatic efficacy of fibrinogen precipitation with varied keratin fraction compositions

In preclinical studies, human hair has demonstrated effective hemostatic properties, potentially attributed to keratin proteins facilitating rapid conversion of fibrinogen to fibrin during coagulation. However, the rational use of human hair keratin for hemostasis remains unclear, given its complex mixture of proteins with diverse molecular weights and structures, leading to variable hemostatic capacity. To optimize the rational utilization of human hair keratin for hemostasis, we investigated the effects of different keratin fractions on keratin-mediated fibrinogen precipitation using a fibrin generation assay. Our study focused on high molecular weight keratin intermediate filaments (KIFs) and lower molecular weight keratin-associated proteins (KAPs) combined in various ratios during the fibrin generation. Scanning electron microscope analysis of the precipitates revealed a filamentous pattern with a broad distribution of fiber diameters, likely due to the diversity of keratin mixtures involved. An equal proportion of KIFs and KAPs in the mixture yielded the most extensive precipitation of soluble fibrinogen in an in vitro study, potentially due to structure-induced exposure of active sites. However, all hair protein samples exhibited diverse catalytic behaviors compared to thrombin, highlighting the potential of utilizing specific hair fractions to develop hair protein-based hemostatic materials with optimized capacity.

Keratin granuloma-associated giant cells in oral squamous cell carcinoma: A blessing in disguise?

Keratin spillage-associated foreign body giant cell granuloma formation is a well-known phenomenon in oral squamous cell carcinoma (OSCC) pathogenesis. It is mainly associated with well-differentiated grade and multi-nucleated giant cells (MGCs) with active engulfment and clearance of keratin debris from the tumor microenvironment. Although not widely investigated, these MGCs are genetically and immunologically programmed for keratin clearance. With this knowledge in mind, we propose that these programmed MGCs might also attack and degrade the tumor cells due to the presence of high and low molecular weight keratin inside the tumor cells. This process can reduce the tumor burden and improves the overall prognosis in OSCC patients. In support of this contention, an improved prognosis has been reported in OSCC patients with keratin granuloma and MGC formation. We also put forth the purposeful induction of keratin granuloma formation in well-differentiated squamous cell carcinoma as an interesting therapeutic opportunity in the future. This could be achieved through intra-lesional injection of natural or synthetic high molecular weight keratin in the stroma of OSCC tissue. Moreover, the possibility of syncytium formation with tumor cells along with granuloma-associated cytokines' impact have also been discussed in the present paper.

GATA binding protein 3 (GATA3) as a marker for metaplastic spindle cell carcinoma of the breast

Spindle cell lesions of the breast comprise a diverse set of tumors; harboring significant histological and immunohistochemical (IHC) overlap. Accurate diagnosis and classification of spindle cell lesions in the breast remains challenging, especially in core biopsies. In the current study, we evaluated a spectrum of spindle cell lesion of the breast with a panel of IHC antibodies in an effort to differentiate metaplastic spindle cell carcinoma from its benign and malignant mimickers. Our study included 92 patients who underwent breast core biopsies or breast resections at Northwell Health who were diagnosed with benign and malignant tumor/tumor-like spindle cell lesions. Tumors subtypes in this the study included: angiosarcoma, nodular fasciitis, fibromatosis, myofibroblastoma, phyllodes tumors (benign, borderline and malignant), primary sarcomas and metaplastic spindle cell carcinoma. Our biomarker panel included high molecular weight keratin (HMWK), CAM5.2, AE1/AE3, p63, CD34 and GATA3. GATA3 expression was significantly higher in metaplastic carcinomas (88.9 % vs 4.1 %, p < 0.001), when compared to other spindle cell lesions. The sensitivity and specificity for detecting metaplastic carcinomas reached 84.2 % and 97.3 %, respectively. Regarding cytokeratin panels, none of the three individual markers were as sensitive or specific for metaplastic breast carcinoma. GATA3 is the most specific and sensitive marker forfor the identification of metaplastic spindle cell carcinoma of the breast.

Primary Clear Cell Sarcoma of the Breast: A Case Report

Abstract Casestudy: Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a primary soft tissue neoplasm exhibiting evidence of melanocytic differentiation. It is an uncommon aggressive tumor that arises in tendons and aponeuroses of the distal extremities. Here, we report the first case of primary CCS of the breast. The patient was a 43-year-old female who presented with a left breast mass and underwent surgical resection at an outside hospital. No history of melanoma or any other malignancies was reported. Grossly, it was described as a 2 x 1.5 x 1.5 cm, well-demarcated, white nodular mass. Microscopic examination showed a malignant neoplasm composed of short spindle cells with ill-defined, eosinophilic cytoplasm and ovoid nuclei with finely stippled chromatin and exhibiting moderate pleomorphism. The lesional cells were arranged in short interlacing fascicles with abundant collagen, with brisk mitotic activity (&amp;gt;15/10 HPF). The differential diagnosis included spindle cell carcinoma, myoepithelial carcinoma and melanocytic neoplasm. The tumor cells were immunoreactive for S-100 protein, SOX10, Mart-1, HMB45 and MiTF, but negative for multiple cytokeratins (including high and low molecular weight keratins), p63, EMA, CEA, Caldesmon, smooth muscle myosin, calponin, desmin, ERG, and CD31, thus confirming melanocytic origin. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization analysis using break-apart probes. Overall, the histomorphology combined with the immunophenotype and cytogenetic characteristics, was most consistent with a CCS. To our knowledge, no primary CCS of the breast has been previously reported in the English language literature.

Xanthogranulomatous epithelial tumor: report of 6 cases of a novel, potentially deceptive lesion with a predilection for young women

Epithelial marker expression and/or epithelial differentiation, as well as “anomalous” expression of keratins, are features of some soft tissue tumors. Recently, we have encountered an unusual mesenchymal tumor composed of bland, distinctly eosinophilic, keratin-positive epithelial cells, which were almost entirely obscured by xanthogranulomatous inflammation. Six cases were identified (5 F, 1 M; 16–62 years (median 21 years)) arising in soft tissue (n = 4) and bone (n = 2) and ranging in size from 2 to 7 cm. The tumors were generally circumscribed, with a fibrous capsule containing lymphoid aggregates, and consisted in large part of a sheet-like proliferation of foamy histiocytes, Touton-type and osteoclast-type giant cells, and chronic inflammatory cells. Closer inspection, however, disclosed a distinct population of uniform, cytologically bland mononuclear cells with brightly eosinophilic cytoplasm arranged singly and in small nests and cords. Overt squamous and/or glandular differentiation was absent. By immunohistochemistry, these cells were diffusely positive with the OSCAR and AE1/AE3 keratin antibodies, and focally positive for high-molecular weight keratins; endothelial and myoid markers were negative and SMARCB1 was retained. RNA-seq identified a PLEKHM1 variant of undetermined significance in one case, likely related to this patient's underlying osteopetrosis. Follow-up to date has been benign. In summary, we have identified a novel tumor of soft tissue and bone with a predilection for young females, provisionally termed “xanthogranulomatous epithelial tumor”. These unusual lesions do not appear to arise from adnexa, or represent known keratin-positive soft tissue tumors, and the origin of their constituent epithelial cells is obscure. The natural history of this distinctive lesion appears indolent, although study of additional cases and longer term follow-up are needed.

Bioinformatics analysis of differentially expressed miRNAs in non-small cell lung cancer.

ObjectiveNon‐small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype‐specific molecular therapeutic procedures.MethodsA total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC.ResultsLUAD and LUSC appear sharply distinct at molecular and pathological level. Let‐7a‐5p, miR‐338, miR‐375, miR‐217, miR‐627, miR‐140, miR‐147b, miR‐138‐2, miR‐584, and miR‐197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2‐1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let‐7a‐5p was significantly down‐regulated in LUAD while miR‐338 was markedly down‐regulated in LUSC. Bioinformatics analyses appeared that let‐7a‐5p directly targets high–molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2‐1) which was associated with tumor progression in LUSC was identified as a target gene of miR‐338.ConclusionsDistinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype‐specific molecular therapeutic target to protect against LUAD and LUSC.

Insight into the Regulatory Function of Human Hair Keratins in Wound Healing Using Proteomics.

Keratins derived from human hair possess excellent wound healing qualities. However, their functional contribution to this process is poorly understood. In this study, the regulatory function of human hair keratins in wound healing is investigated using proteomic analysis by dividing keratins into different groups based on their molecular weight distributions: low molecular weight keratins (LMWK, 10-30 kDa), medium molecular weight keratins (MMWK, 30-50 kDa), and high molecular weight keratins (HMWK, >50 kDa). Keratin hydrogels with different molecular weights exhibit various morphologies, rheological properties, degradation rates, and wound healing activities. Using proteomic analysis, LMWK and HMWK hydrogels exhibit a stronger regulatory ability for wound healing at days 1 and 7, respectively. The major functions of LMWK during wound healing are regulation of cells communication and function. In contrast, proteins associated with energy metabolism are significantly expressed after HMWK hydrogel treatment at day 1, and these play an important role in cellular growth and reactive oxygen species scavenging at day 7. These results demonstrate that the wound healing qualities of human hair keratins are influenced by their molecular weight distribution, and the proteomic analysis sheds new light on the regulatory function of human hair keratins during wound healing.

Comparison of Immunostaining with Hematoxylin-Eosin and Special Stains in the Diagnosis of Cutaneous Macular Amyloidosis

BackgroundAlthough macular amyloidosis is a relatively rare disease, it is a common cutaneous disease in Asia and the Middle East. On hematoxylin and eosin (H&E) stained slides, early lesions could easily be missed without the use of special stains and/or immunohistochemistry.MethodsWe enrolled 42 patients with the clinical impression of macular amyloidosis who had undergone two 4-mm punch biopsies from 2015 to 2016 at a dermatology clinic affiliated to Shiraz University. Besides, 14 cases with a clinical diagnosis other than macular amyloidosis were selected as the negative control group. Congo red, crystal violet, and immunohistochemical (IHC) staining of CK5 and high molecular weight keratin (HMWK) were performed for each specimen.ResultsH&E slides showed globular depositions in 15 (35.7%) out of 42 patients. None of the patients showed apple-green birefringence with Congo red stain. Evaluation of crystal violet stained sections revealed purplish violet amyloid deposits in 15 (35.7%) patients. IHC study showed expression of CK5 in 52.4% and HMWK in 50% of the patients, which was not a significant difference (p = 0.715). The findings of both IHC markers had a significant difference with H&E stains (p = 0.039) and crystal violet (p = 0.008). Additionally, we found that two punch biopsies from two sites in the involved area did not have a significant preference over one punch biopsy. All of the cases in the control group were negative for amyloid deposition in H&E, special stains, and IHC stained slides as expected.ConclusionsIHC evaluation using CK5 and HMWK might be a useful tool for diagnosing macular amyloidosis.

Functionalized Keratin as Nanotechnology-Based Drug Delivery System for the Pharmacological Treatment of Osteosarcoma.

Osteosarcoma therapy might be moving toward nanotechnology-based drug delivery systems to reduce the cytotoxicity of antineoplastic drugs and improve their pharmacokinetics. In this paper, we present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma. The nanoparticles are prepared from high molecular weight and hydrosoluble keratin, suitably functionalized with the photosensitizer Chlorin-e6 (Ce6) and then loaded with the chemotherapeutic drug Paclitaxel (PTX). This multi-modal PTX-Ce6@Ker nanoformulation is prepared by both drug-induced aggregation and desolvation methods, and a comprehensive physicochemical characterization is performed. PTX-Ce6@Ker efficacy is tested on osteosarcoma tumor cell lines, including chemo-resistant cells, using 2D and 3D model systems. The single and combined contributions of PTX and Ce6 is evaluated, and results show that PTX retains its activity while being vehiculated through keratin. Moreover, PTX and Ce6 act in an additive manner, demonstrating that the combination of the cytostatic blockage of PTX and the oxidative damage of ROS upon light irradiation have a far superior effect compared to singularly administered PTX or Ce6. Our findings provide the proof of principle for the development of a novel, nanotechnology-based drug delivery system for the treatment of osteosarcoma.

A Rare Case of Uterine Leiomyosarcoma With Metastasis to the Colon

Laeeq Butt, MD, MBA, Rajiv Mallipudi, MD, Swami Nathan, MD A Rare case of Uterine Leiomyosarcoma with Metastasis to the Colon and Small Bowel Introduction: Uterine leiomyosarcoma is an extremely rare and aggressive malignancy with an overall poor prognosis. It typically metastasizes through hematogenous dissemination to the lungs, bones and brain. However, there have not been many cases of metastasis to the colon. In reported cases the patients presented with acute abdomen secondary to uterine leiomyosarcoma invasion of the small bowel or colon. Here we present an extremely rare case of a leiomyosarcoma of the uterus with metastasis to the colon.Figure: P1: Colonoscopy image of the tumor.Figure: P2: Colon mass pathology shows Spindle Cells (elongated narrow cells) indicative of Sarcoma.Case: 48 year old female with uterine leiomyosarcoma with metastasis presented with acute blood loss anemia, small bowel obstruction and intussusception. Colonoscopy showed a 20mm ascending colon mass with pathology consistent with high grade sarcoma consistent with metastatic leiomyosarcoma (P1,P2). CT scan showed hypodensity in the right quadriceps muscle of 1.2 x 1 cm and intraluminal metastatic lesions causing intermittent intussusception and dilated small bowel loops. Three metastatic lesions in the lung were also identified (P3). Immunohistological staining showed that the colon mass was strongly positive for C-kit, DOG1 and negative for CD34. Karetin stains (MN116, AE1.3 and high molecular weight Keratin) did not stain the tumor. Key sarcoma markers such as Desmin, Actin and smooth muscle were negative. Metastatic tumors on occasion can be dedifferentiated and fail to express expected markers; therefore, pathologist believed that given recent diagnosis this colon tumor must be metastasis from the uterine leiomyosarcoma. Patient was offered palliative chemotherapy and surgical treatment and was lost to follow up post discharge.Figure: P3: Chest X-Ray with metastatic lesions identified.Conclusion: Melenoma is the most comon tumor that metastesizes to the colon. Metastasis to small bowel and colon from uterine leiomyosarcoma is extremely rare and is a sign of advanced disease. The more common sites for metastasis are lung, liver, abdomen, pelvic/aortic lymph nodes. Bone and brain are less common. It is important to differentiate between primary tumors of the colon versus metastatic and immunohistochemistry can be utilized to differentiate between the two. Metastasis to the heart is also possible via direct extension, hematogenous spread, and implantation or via lymphatic route.

The diagnostic value of TTF1, P63, HMWK [34βE12], CK7, and CD56 immunostaining in classification of lung carcinoma

The histologic distinction of small cell from non-small cell lung carcinoma and correct identification of all subtypes of lung carcinoma are very important in treatment management. The main method for histologic classification of lung tumors is based on morphology. However, in small bronchoscopic biopsies in particular, distinction is very difficult upon morphology alone. The current study aimed at evaluating the utility of a panel of antibodies, consisting of thyroid transcription factor (TTF-1), P63, high molecular weight keratin [HMWK (34βE12)], cytokeratin (CK7), and cluster of differentiation (CD56) for accurate distinction of bronchogenic carcinomas. Bronchoscopic biopsies of 60 lung carcinoma cases including 20 small cell carcinomas, 20 adenocarcinomas, and 20 squamous cell carcinomas (SCCs) with typical morphologic features were selected. All these cases were immunohistochemically stained for TTF-1, P63, HMWK (34βE12), CK7, and CD56. All immunostained slides were scored as either positive or negative. The mean age of the patients was 60 years; ranged from 35 to 81. Sixteen patients were female and 44 were male. All adenocarcinomas were positive for CK7 and most of them (18/20; 90%) were positive for TTF-1. Most of small cell lung carcinomas were positive for TTF-1 (17/20; 85%), and CD56 (18/20; 90%). All squamous cell carcinomas (SCCs) were negative for TTF-1, but most of them were positive for HMWK (34βE12) and P63. The obtained data showed that TTF-1, P63, CK7, CD56 and/or 34βE12 represent a useful panel of antibodies to identify lung carcinoma subtypes in small bronchoscopicbiopsies.

Application of Dissolved Wool Keratin in Anti-Pilling Processing

In the current study, a novel wool dissolving system based on NaHSO3, azone and LKZ-610 (Trisubstituted organic phosphorus, an anti-shrink finishing agent for wool and cashmere) was prepared and employed to process wool fibers into keratin solution at 90°C for 7 hrs, where 65g wool fibers, 30g NaHSO3 and 5g azone were dissolved in 1L LKZ-610, resulting in high molecular weight keratin solution. The anti-pilling rating reached at Grade 4.5 with good hand when the cashmere fabric was treated for 50min at 50°C in the previously prepared wool keratin solution under the condition of 1:20 bath ratio, 8% owf keratin solution and 5% owf LKZ-610.

Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis.

Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), nuclear alignment (68%), small papillary tufts (32%), focal branching papillae (27%), and prominent papillary structures (9%). Carbonic anhydrase IX uniformly revealed diffuse positivity. Staining for cytokeratin 7 (CK7) was focal (64%) or negative (18%) in most tumors (82%); however, >50% labeling was present in 4 (18%). Reactivity for both CD10 and α-methyl-acyl-CoA-racemase (AMACR) was usually present (median 80% and 60% of cells). Seven tumors showed reactivity for high-molecular weight keratin (32%). Chromosome 3p loss was confirmed in 15 tumors (68%), including 4/7 with labeling for high-molecular weight keratin or >50% reactivity for CK7. A discordant immunohistochemical pattern typically correlates with loss of material from chromosome 3p in tumors with incomplete morphology of clear cell papillary renal cell carcinoma, supporting classification as clear cell renal cell carcinoma. Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR.

Clinicopathological features and prognosis of renal cell carcinoma with sarcomatoid differentiation

To study the clinicopathological features and prognosis of renal cell carcinoma with sarcomatoid differentiation (RCCS). The clinical data and pathological materials of 18 RCCS cases were retrospectively reviewed.The follow up data were available in 13 RCCS cases, and were compared with the follow up data of 20 cases of clear cell renal cell carcinoma (RCC). The 18 RCCS patients included 14 males and 4 females, and were 49-79 years old (mean age: 62 years old). On gross examination, the tumor size was 3-19 cm in diameter (mean diameter: 9.8 cm). Histologically, all tumors were composed of a mixture of typical RCC with sarcomatoid component, including 9 clear cell RCC, 3 chromophobe RCC and one papillary RCC. The sarcomatoid components included 9 cases of fibrosarcoma, 3 cases of leiomyosarcoma, 5 cases of malignant fibrous histocytoma and one case of undifferentiated sarcoma. Immunohistochemistry showed that the sarcomatoid components were strongly vimentin-positive in 18 cases, and one or more epithelial markers (EMA, AE1/AE3, CK7, CK18) were expressed to varying degrees in 14 cases, but the high-molecular weight keratin 34βE12 was scarcely expressed. The sarcomatoid components presented positive expressions of CAIX in 88.9% (16/18) and CD10 in 72.2% (13/18) cases. Among the 18 RCCS patients, 13 patients were followed-up: 9 patients died in 1-25 months after the surgery, of which 5 cases died of lung or bone metastasis, and 4 patients died of systemic failure. The twenty RCC cases without sarcomatoid differentiation were followed up for 3-65 months after the surgery, and the majority of them was alive uneventfully except for 2 cases who died of lung or bone metastasis of the tumor. The Kaplan-Meier survival analysis showed that the median survival time of the 18 RCCS patients was 8 months, while that of the 20 RCC cases without sarcomatoid differentiation was 62 months (P<0.001). The presence of sarcomatoid differentiation in renal cell carcinoma indicates highly aggressive behavior and poor prognosis. The positive expressions of the immune markers CAIX and CD10 may play important roles in the transformation from renal cell carcinoma to sarcomatoid component.

Ectopic Prostate in the Uterine Cervix / Female Genital Tract Including Vagina and Vulva: A Review of the Literature

Background: Men are known to have prostate glands but not women. The thought of prostate gland occurring in the female genital tract in women would be petrifying to all clinicians and people who are not aware of its biological behavior. Ectopic prostate in the uterine cervix (EPIUC) and the female genital tract (FGT) is very rare. Aim: To review the literature on EPIUC/FGT and to document its biological behavior. Methods: Information obtained from 17 references, was used for the literature review on EPIUC/FGT. Results: Few cases of EPIUC/FGT have been reported at ages ranging between 21 and 82 years EPIUCs/FGTs may be diagnosed incidentally in biopsies of the cervix/vagina/vulva, or in hysterectomy specimens or they may mimic leiomyomas. Histological examination of cervical biopsies or of the cervix in hysterectomy specimens reveals ducts and acini some papillary or cribriform, with prominent squamous metaplasia EPIUCs/FGTs show positive ImmunohistoReview Article Venyo; BJMMR, 9(12): 1-14, 2015; Article no.BJMMR.18101 2 chemical staining for prostate specific antigen (PSA), prostatic-specific acid phosphatase (PSAP [PAP]), high molecular weight keratin (for basal cells). EPIUCs reported so far have exhibited benign behavior. Conclusions: Information obtained from the literature would indicate that EPIUCs / FGTs are rare and so far have exhibited benign behavior. Clinicians should report cases of EPIUC/FGT in order to establish whether or not EPIUCs/FGTs may or may not develop into carcinomas in the future.

Remodelling of the skin during metamorphosis in the Italian newt (Lissotriton italicus) (Amphibia, Urodela): localization pattern of keratins, stromelysin-3 (MMP-11), and pan-cadherin

During amphibian metamorphosis, modifications of several important body systems take place involving different molecular mechanisms driving, among other, cell differentiation, cell–cell adhesion, and extracellular matrix turnover. Amphibians have been used as a classic model to investigate organs remodelling, including the skin; however, previous studies on metamorphosis have examined, for the most part, anurans, whereas only a few reports have considered urodeles. The main goal of this study was to evaluate the presence of keratins in the epidermis of the Italian newt (Lissotriton italicus). In order to assess the putative differential expression of keratins, we immunodetected cytokeratin type I, type II, and high molecular weight (HMW) during the larval, pre-metamorphic, and adult phase. Our results clearly indicated that keratins expression changes as the epidermis modifies during the functional maturation; interestingly, HMW keratins showed a strong immunopositivity in adult, thus suggesting that, in urodeles, these keratins become expressed in adult epidermis. Moreover, by using a monoclonal antibody against pan-cadherin, we demonstrated that in L. italicus epidermis during pre-metamorphic stages, the conversion from larval to adult type is not completed in whole epidermis; we also showed the strong spatiotemporal correlation of stromelysin-3 expression with tissue remodelling in L. italicus skin. Considering that skin remodelling in urodeles is a topic relatively neglected, our findings will contribute to fill a gap in the existing research literature; moreover, these data emphasize that unexpected results could be obtained when different model systems were used.

Microcystic variant malignant mesothelioma presenting as a localized paraspinal mass

A 58-year-old man presented with productive cough and fever. Computed tomography (CT) scan of the chest showed an upper right paraspinal mass. CT-guided fine-needle aspiration biopsy showed lobules of vacuolated cells against a background of myxoid material. The cells demonstrated moderate to severe nuclear atypia and occasional mitoses. Immunohistochemistry revealed tumor cells to be immunoreactive for calretinin, WT-1, D2-40, cytokeratin (CK) 7, AE1/AE3, high molecular weight keratin, vimentin and epithelial membrane antigen, and negative for thyroid transcription factor-1, Ber-EP4, carcinoembryonic antigen, S100 protein, CK20, and CDX2. The combined morphologic and immunohistochemical findings confirmed the diagnosis of microcystic variant of localized malignant mesothelioma. The subsequent lung resection showed a pleural-based mass in the right upper lobe and confirmed the diagnosis. Awareness of the existence of unusual morphologic variants and localized forms of mesothelioma are necessary to avoid misdiagnosis of fine needle biopsy samples. Recognition of characteristic cytomorphologic features along with optimal use of panel of immunohistochemistry studies is crucial for making a specific diagnosis.

A collecting duct carcinoma producing carcinoembryonic antigen and Ca-125 in a 29-year-old woman

Collecting duct carcinoma is a rare renal malignant neoplasm, arising from the medullary collecting duct and accounting for less than 1% of renal cell carcinomas. It is more common in middle-aged men and is usually presented with hematuria, abdominal mass and back or flank pain. Its immunohistochemical analysis detects the expression of various markers, such as low and high molecular weight keratins, Ulex europaeus agglutinin-1, epithelial membrane antigen and peanut lectin. Here, we present a case of a 29-year-old woman with CDC presented with back pain and supraclavicular lymphadenopathy that produced carcinoembryonic antigen and CA-125.