Foreign Body Giant Cells Research Articles

Identification of a Unique Morphological Pattern for the Diagnosis of Fungal Rhinosinusitis.

Fungal rhinosinusitis (FRS) is a relatively common, but often misdiagnosed disease of paranasal sinuses. The FRS is classified into invasive and non-invasive forms. The non-invasive form includes fungal ball and allergic FRS, and invasive form includes acute invasive FRS, chronic invasive FRS, and granulomatous FRS. Invasive fungal infections are associated with high morbidity and mortality, hence requiring urgent medical and surgical intervention. The histomorphology can help identify certain fungal organisms that cannot be cultured or are rarely visible in exudates. The morphologic diagnosis of tissue invasive and non-invasive fungal infection is essential for appropriate treatment. We analyzed cases of rhinosinusitis from 2017 to 2019 in Pathology Department at a tertiary care cancer hospital, Lahore, Pakistan. All clinical information was retrieved from patient records. Paraffin-embedded tissue blocks were stained with hematoxylin and eosin (H&E), special Grocott methenamine silver stain (GMS), and periodic acid Schiff stain (PAS) according to standard protocol. They were reviewed by two pathologists blinded by fungus status. A total of 169 cases of rhinosinusitis were reviewed. FRS comprised 146 (86.4%) of them. The mean age of patients with FRS was 32.8±14 years. The male:female ratio was 1.4:1. Maxillary sinus was the main site of involvement in 39 (27%) FRS cases. Aspergillus was identified in 117 (80.1%) cases of FRS. The culture reports were available in 44/146 (30.14%) FRS cases. They were negative in 22/44 (50.0%), and Aspergillus species were isolated in 18/44 (40.9%) cases of FRS. There were 84 (57.5%) cases of non-invasive FRS and 59 (40.4%) cases of invasive FRS. Among invasive FRS, there were 56 (38.4%) chronic granulomatous FRS cases including mixed patterns. Majority cases, 54 (96.4%), of chronic granulomatous FRS showed a unique crowded giant cell pattern comprising of foreign body and Langhans type giant cells. These giant cells were arranged closely forming irregular non-caseating granulomas surrounded by lymphocytes and fibrosis. Interestingly, the giant cells were scattered haphazardly without forming a granuloma as well. Fungal organisms were identified in all 56 cases of chronic granulomatous FRS. Histologically, predominant organism was Aspergillus in 48 (85.7%) on GMS and PAS stain. Our study observed a unique crowded giant cell pattern, which is a hallmark of invasive fungal infection. If pathologists are familiar with this unique pattern, they can make a quick and accurate diagnosis on histology. The physician can start antifungal treatment timely for better prognosis.

Histopathological changes in tissues surrounding vagal nerve stimulation generators: A retrospective analysis of revision surgeries.

Vagal nerve stimulation (VNS) is an effective treatment for patients with epilepsy, depression, and other neuropsychiatric conditions. Understanding the tissue changes associated with VNS devices is crucial for optimizing patient outcomes and device development. This study aimed to investigate the histopathological changes in the tissues surrounding the VNS generator and explore potential correlations with clinical factors and battery performance. A total of 23 patients who underwent VNS generator revision surgery owing to battery depletion were included. Tissue samples from the areas surrounding the VNS generator were obtained and analyzed for histopathological changes. Demographic and device-related variables were also recorded. Capsule formation was observed in all patients. Acute inflammation were not detected in any case. Perivascular lymphocytic infiltration, foreign-body giant cell reaction (FBGCR), and calcification were observed in 8.7%, 26.1%, and 43.5% of patients, respectively. Crystalloid foreign body appearance was noted in 4 patients. The median output current of the generator was higher in patients with lymphocytic infiltration than in those without lymphocytic infiltration. The median off time was higher in patients with skin retraction than in those without skin retraction. Moreover, discomfort was associated with the presence of FBGCR. Our study provides insights into the tissue changes associated with the VNS generator, with capsule formation being a common response. Crystalloid foreign body appearance was not reported previously. Further research is needed to understand the relationship between these tissue changes and VNS device performance, including the potential impact on battery life. These findings may contribute to VNS therapy optimization and device development.

Nanotextured porous titanium scaffolds by argon ion irradiation: Toward conformal nanopatterning and improved implant osseointegration.

Stress shielding and osseointegration are two main challenges in bone regeneration, which have been targeted successfully by chemical and physical surface modification methods. Direct irradiation synthesis (DIS) is an energetic ion irradiation method that generates self-organized nanopatterns conformal to the surface of materials with complex geometries (e.g., pores on a material surface). This work exposes porous titanium samples to energetic argon ions generating nanopatterning between and inside pores. The unique porous architected titanium (Ti) structure is achieved by mixing Ti powder with given amounts of spacer NaCl particles (vol % equal to 30%, 40%, 50%, 60%, and 70%), compacted and sintered, and combined with DIS to generate a porous Ti with bone-like mechanical properties and hierarchical topography to enhance Ti osseointegration. The porosity percentages range between 25% and 30% using 30 vol % NaCl space-holder (SH) volume percentages to porosity rates of 63%-68% with SH volume of 70 vol % NaCl. Stable and reproducible nanopatterning on the flat surface between pores, inside pits, and along the internal pore walls are achieved, for the first time on any porous biomaterial. Nanoscale features were observed in the form of nanowalls and nanopeaks of lengths between 100 and 500 nm, thicknesses of 35-nm and heights between 100 and 200 nm on average. Bulk mechanical properties that mimic bone-like structures were observed along with increased wettability (by reducing contact values). Nano features were cell biocompatible and enhanced in vitro pre-osteoblast differentiation and mineralization. Higher alkaline phosphatase levels and increased calcium deposits were observed on irradiated 50 vol % NaCl samples at 7 and 14 days. After 24 h, nanopatterned porous samples decreased the number of attached macrophages and the formation of foreign body giant cells, confirming nanoscale tunability of M1-M2 immuno-activation with enhanced osseointegration.

Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.

Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites. Human innate immune macrophages were verified as essential to biomaterial rejection in this model and were capable of cross-talk with mouse fibroblasts for collagen matrix deposition. Cytokine and cytokine receptor array analysis confirmed core signaling in the fibrotic cascade. Foreign body giant cell formation, often unobserved in mice, was also prominent. Last, high-resolution microscopy coupled with multiplexed antibody capture digital profiling analysis supplied spatial resolution of rejection responses. This model enables the study of human immune cell-mediated fibrosis and interactions with implanted biomaterials and devices.

CLINICAL AND HISTOPATHOLOGICAL FEATURES OF ORAL COMPLICATIONS AFTER INJECTABLE DERMAL FILLER: A CASE REPORT

A 55-year-old female patient that sought the stomatology clinic complaining of a nodule that appeared near the lower gum about one month ago. The patient reported that after compressing the nodule, a visible pink mass appeared on the oral mucosa near the lower gingiva. During anamnesis, the patient reported that she had undergone facial dermal filling with hydroxyapatite microspheres about one year ago. On physical examination, a well-delimited, irregularly shaped, solid-consistent, pinkish-yellowish mass was observed, covered by intact mucosa, measuring approximately 8 × 12mm. The main diagnostic hypothesis was foreign body reaction to filling material. During an incisional biopsy, it was observed that the material had a rubbery consistency and was adhered to the mucosa and underlying muscle tissue. Anatomopathological examination revealed rounded structures containing granular material surrounded by mononuclear inflammatory infiltrate and foreign body-type giant cells. The diagnosis was foreign body granuloma. Patient remains under clinical follow-up. A 55-year-old female patient that sought the stomatology clinic complaining of a nodule that appeared near the lower gum about one month ago. The patient reported that after compressing the nodule, a visible pink mass appeared on the oral mucosa near the lower gingiva. During anamnesis, the patient reported that she had undergone facial dermal filling with hydroxyapatite microspheres about one year ago. On physical examination, a well-delimited, irregularly shaped, solid-consistent, pinkish-yellowish mass was observed, covered by intact mucosa, measuring approximately 8 × 12mm. The main diagnostic hypothesis was foreign body reaction to filling material. During an incisional biopsy, it was observed that the material had a rubbery consistency and was adhered to the mucosa and underlying muscle tissue. Anatomopathological examination revealed rounded structures containing granular material surrounded by mononuclear inflammatory infiltrate and foreign body-type giant cells. The diagnosis was foreign body granuloma. Patient remains under clinical follow-up.

A Curious Case of Omental Oxalate Crystals in a Patient With Struma Ovarii: Pointers to an Unusual Clinicopathological Scenario.

Percutaneous image-guided biopsies are becoming increasingly common in routine pathology practice, with the greater omentum emerging as a common target. We present herein an account of a middle-aged lady with a complex ovarian mass, omental thickening, and raised serum CA125; clinically suspected to have advanced ovarian malignancy. Fine needle aspiration cytology (FNAC) from the ovarian mass was inconclusive. Omental biopsy revealed only refractile, birefringent crystalline material with surrounding foreign body giant cell reaction; thus surprising the clinical team. Subsequent resection of the ovarian mass showed a teratoma composed exclusively of thyroid tissue, diagnosed as struma ovarii. The omental crystals, interpreted as calcium oxalate crystals, were possibly a consequence of colloid seeding during the ovarian mass FNAC.

(112) An Experimental Animal Study of the Histopathological Effect of Collagen Fleece (TachoSil) Patch of Tunica Albuginea Defects Associated with Penile Surgery

Abstract Introduction A penile tunica defect may arise during penile prosthesis surgery or reconstruction of the penis in patients with Peyronie’s disease. Collagen fleece (TachoSil) was recently reported in penile surgery to cover the tunica defect with reported clinical success. However, it is not known what the histological outcomes of these grafts are in the penis. Objective We study the novel application of TachoSil graft in an experimental animal model. We looked at the regeneration of tunica albuginea, development of inflammation and fibrosis, and histopathological effect on the underlying cavernous tissue. Methods Seven adult male Sprague Dawley rats were used. All procedures were carried out under general inhalation anesthesia. The penis was degloved through a circumferential subcoronal incision. A longitudinal 1x10 mm defect was created at the base of the lateral aspect of the penis. A TachoSil patch (Takeda, Japan) was applied to the defect in six rats and Surgicel (Ethicon) in one. The penile skin covering is then restored and fixed with interrupted 5-6 zero absorbable sutures. At two months, the rat penis was evaluated for excision. Euthanasia was carried out with an overdose of inhalation anesthesia and chest opening. The excised penis was examined by hematoxylin and eosin and trichrome stains. Results At the time of surgery, the rats’ weight was 390 gm (SD 33.8). All rats with TachoSil showed normal-looking penis at two months with complete healing, no scaring, tethering, or gross inflammatory features. The penis of three rats with a Tachosil patch was harvested at two months postoperatively. It showed histopathology of fibrosis, chronic inflammation, and foreign body giant cell reaction at the site of the patch. There was no generation of a new tunica albuginea, no new vascularity or distinct fibrous layer development. The underlying corpus cavernous tissue was not affected by any inflammatory or pathological reaction. One rat died on the 6th postoperative day. Postmortem showed massive gastrointestinal bleeding, intraperitoneal hemorrhage, and punctate hemorrhages of the parenchyma of both suprarenal glands, both kidneys, and the liver. A clinical diagnosis of DIC was made. Histopathology of the penis, however, did not show micro thrombosis. The fifth rat with a Surgicel patch showed immediate hematoma of the penis controlled by compression. After two months, during harvesting of the penis, large pockets of pus were seen spreading from the site of the patch to surrounding structures. Histopathology showed chronic inflammation and fibrosis extending into the corpus cavernosum. The sixth and seventh rats showed normal penis external appearance at two months and were left surviving for harvest at four months. Conclusions Tachosil patching of penile tunica albuginea defect forms a distinctive barrier against inflammation protecting the underlying corpus cavernosum. However, no regeneration of tunica defect is observed at two months. DIC is a potential complication of systemic absorption of TachoSil. Disclosure No

IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells

BackgroundThe biomaterial integration depends on its interaction with the host immune system. Monocyte-macrophage lineage cells are immediately recruited to the implant site, polarized into different phenotypes, and fused into multinucleated cells, thus playing roles in tissue regeneration. IL-1R-associated kinase 4 (IRAK4) inhibition was reported to antagonize inflammatory osteolysis and regulate osteoclasts and foreign body giant cells (FBGCs), which may be a potential target in implant osseointegration.MethodsIn in-vitro experiments, we established simulated physiological and inflammatory circumstances in which bone-marrow-derived macrophages were cultured on sand-blasted and acid-etched (SLA) titanium surfaces to evaluate the induced macrophage polarization, multinucleated cells formation, and biological behaviors in the presence or absence of IRAK4i. Then, bone marrow stromal stem cells (BMSCs) were cultured in the conditioned media collected from the aforementioned induced osteoclasts or FBGCs cultures to clarify the indirect coupling effect of multinucleated cells on BMSCs. We further established a rat implantation model, which integrates IRAK4i treatment with implant placement, to verify the positive effect of IRAK4 inhibition on the macrophage polarization, osteoclast differentiation, and ultimately the early peri-implant osseointegration in vivo.ResultsUnder inflammatory conditions, by transforming the monocyte-macrophage lineage cells from M1 to M2, IRAK4i treatment could down-regulate the formation and activity of osteoclast and relieve the inhibition of FBGC generation, thus promoting osteogenic differentiation in BMSCs and improve the osseointegration.ConclusionThis study may improve our understanding of the function of multinucleated cells and offer IRAK4i as a therapeutic strategy to improve early implant osseointegration and help to eliminate the initial implant failure.

Cd13 controls myeloid cell-cell fusion

Abstract Macrophages have the ability to undergo phenotypic and functional changes in response to microenvironmental cues. One such change is the formation of multinucleated giant cells (MGCs) via intercellular fusion triggered by certain bacterial or parasitic infections or implantation of medical devices that induces deleterious MGC formation in response to the foreign body. Despite advances in biomaterials, implants ultimately corrode to produce particles that initiate a foreign body response characterized by macrophage fusion into pro-inflammatory, Foreign Body Giant Cells that directly define the pathology of loosening of medical implants. We have shown that the transmembrane protein CD13 is a multifunctional molecule that regulates diverse processes such as cell-cell adhesion, receptor endocytosis and recycling and organization of the actin cytoskeleton, all of which are critical in cell-cell fusion. We demonstrate that subcutaneous foreign implants in CD13 KOmice produce significantly more MGCs with increased levels of plasma pro-inflammatory cytokines. In vitro induction of fusion in CD13-deficient myeloid progenitors generated from bone marrow resulted in hyperfusion to generate MGCs that were considerably larger in size and contained many more nuclei than those from wild type progenitors, suggesting that CD13 regulates MGC formation at the stage of fusion. While expression of the key fusion proteins are typically downregulated in mature cells post-fusion, expression of these proteins is sustained at high levels in multinucleated cells lacking CD13. Thus, CD13 acts as a brake to prevent aberrant myeloid cell-cell fusion and may be a novel therapeutic target in pathological conditions mediated by abnormal cell fusion. Supported by grants from NIH (1R21 AI15 )

The Influence of Design Modifications and Microstructured Surface Topographies on Bleb Survival after Glaucoma Tube Shunt Implantation.

Lowering intraocular pressure (IOP) by placement of a glaucoma shunt is an effective treatment for glaucoma. However, fibrosis of the outflow site can hamper surgical outcome. In this study, the antifibrotic effect of adding an endplate (with or without microstructured surface topographies) to a microshunt made of poly(styrene-block-isobutylene-block-styrene) is investigated. New Zealand white rabbits are implanted with a control implant (without endplate) and modified implants. Afterward, bleb morphology and IOP is recorded for 30 days. After killing of the animals, eyes are collected for histology, Addition of an endplate extended bleb survival, Topography-990 has the longest recorded bleb-survival time. Histology reveals that the addition of an endplate increases the presence of myofibroblasts, macrophages, polymorphonuclear cells, and foreign body giant cells compared to the control. However, an increased capsule thickness and inflammatory response are observed in the groups with surface topographies, The addition of an endplate results in prolonged bleb survival, demonstrating that engineering of the shape of glaucoma implants could prolong bleb functionality. Future research should further elaborate the effect of surface topographies on long-term bleb survival, since an increased presence of pro-fibrotic cells and increased capsule thickness are observed compared to the control.

Granulomatous reaction as a postherpetic isotopic response after primary varicella infection in a healthy adult

We report the first case of post-herpetic isotopic reaction (PHIR) after primary varicella infection in a healthy adult. PHIR refers to the development of new skin lesions at sites where prior herpetic skin lesions have been resolved. Herpes zoster is the most common cause of PHIR; however, only a few cases of PHIR due to primary varicella infections have been reported. Postherpetic isotopic reaction (PHIR) refers to the development of new skin lesions at sites where prior herpetic skin lesions have been resolved. Herpes zoster (HZ) is the most common cause of PHIR; however, only a few cases of PHIR due to primary varicella infections have been reported. A 22-year-old Japanese man with no relevant medical history presented with multiple vesicles throughout the body. The patient was diagnosed with primary varicella infection based on a positive Tzanck test. Three weeks after onset, new skin eruptions appeared in the regions affected by the primary rash. He had multiple nodules of 5–8 mm size and hues ranging from red to normal skin on his face, trunk, and limbs (Figure 1A,B). He had been vaccinated against varicella during childhood. No abnormal findings were observed except for slightly low immunoglobulin (Ig) A and IgG (IgM: 37 mg/dL, IgA: 63 mg/dL, IgG: 734 mg/dL) in blood tests. Viral antibody examination revealed varicella-zoster virus (VZV)-IgM enzyme-linked immunosorbent assay (EIA) and VZV-IgG EIA titers of 0.03 and 6.8, respectively (both tests are positive at ≥4.0), indicating a previous infection. Histological findings showed epithelioid cells and granulomatous foreign body giant cells within the upper dermis, surrounded by marked neutrophilic and lymphocytic infiltration. No caseous necrosis, inclusion bodies, or residual viral particles were observed (Figure 1C,D). The patient was diagnosed with granulomatous reaction as PHIR after primary varicella infection. The nodules gradually improved with topical steroid, and no recurrence was noted. Postherpetic isotopic reaction is a type of Wolf's isotope reaction (WIR), and some argue that WIRs are Koebner reactions.1 However, Koebner reactions generally indicate the appearance of the same preexisting dermatosis on the injured skin. In the present case, a completely different eruption appeared after the primary rash. Thus, it was appropriate to describe it as a PHIR. Various skin manifestations have been reported in PHIR, with granulomatous dermatitis being the most common. According to Wang et al., the pathogenesis of granulomatous reaction as PHIR possibly encompasses post-infection nerve damage and residual virus particles, which may induce secretion of interleukin-4 and other chemokines, promote infiltration of inflammatory cells, and locally modulate immune and angiogenic responses.2 Less nerve damage associated with primary varicella compared to that associated with HZ may be a reason for the infrequent PHIR phenomenon following primary varicella infection. Several pediatric cases of granulomatous reactions as PHIR after primary varicella have been reported previously.3-6 Two PHIR cases in adults were previously reported, but the patients were immunosuppressed hosts with myelogenous leukemia. Immunocompromised patients are susceptible to greater nerve damage by VZV.7 This is the first case of PHIR after varicella infection in a healthy adult. Histological findings supported the possibility of a hyperimmune response to residual viral particles, resulting in granulomatous dermatitis. Blood samples showed a slightly low level of immunoglobulins, but no other abnormalities were observed. Although the cause is unclear, the patient should be followed carefully for the future development of immune system diseases. Further studies are required to understand the mechanisms underlying PHIR after varicella infection. The authors declare no conflict of interest. Informed consent: Informed consent was provided by the patient, and approval was received. Approval of the research protocol: N/A. Registration No. of the study/trial: N/A. Animal studies: N/A. The data that support the findings of this study are available from the corresponding author, Y. W., upon reasonable request.

IN VIVO LIGAMENTOGENESIS IN EMBROIDERED POLY(LACTIC-CO-Ε-CAPROLACTONE) / POLYLACTIC ACID SCAFFOLDS FUNCTIONALIZED BY FLUORINATION AND HEXAMETHYLENE DIISOCYANATE CROSS-LINKED COLLAGEN FOAMS

Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This given study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or gas fluorination combined with the foam (F+coll). Cell free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, biomechanical properties, cell vitality and content, histopathology of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed.Implantation of the scaffolds did not negatively affect mice weight development and organs, indicating biocompatibility. All scaffolds maintained their size and shape for the duration of the implantation. A high cell viability was detected in the scaffolds prior to and following implantation. Coll or F+coll scaffolds seeded with cells yielded superior macroscopic properties when compared to the controls. Mild signs of inflammation (foreign-body giant cells, hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable in vivo, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in the in vivo compared to the samples cultured 1 week in vitro, but did not differ between scaffold subtypes, except for a higher maximum force in F+coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering.(shared first authorship)Acknowledgement: The study was supported by DFG grants SCHU1979/9-1 and SCHU1979/14-1.

Epidermoid Cyst: An Esthetic Challenge, If Neglected-A Comprehensive Analysis of 217 Cases.

An epidermoid cyst is a benign keratin-filled cyst, commonly located in the face, scalp, neck, and trunk. Although it is a common benign cystic neoplasm, large series of analyses in English literature are still scarce. To comprehend the clinical and pathological variation of epidermoid cysts in the sub-Himalayan region of India, as well as their clinical implications for late diagnosis, a retrospective study on epidermoid cysts was conducted. This was a retrospective observational study conducted on 217 cases of epidermoid cyst subjected for fine-needle aspiration cytology over a period of 3.6 years (from 2018 to 2021). The clinical details and other epidemiological data were archived from the pathology requisition forms. It showed slight male preponderance with head and neck site as the most common area. Most patients were adults. Few uncommon sites were also seen namely breast, parotid, epididymis, and tonsils. Few large lesions were identified measuring up to 10 cm. The skin changes were seen in 5.5% cases, 0.9% cases show extreme ulceration, and 4.1% cases show foreign body giant cell reactions. Due to the province's steep terrain and limited access to medical services, the majority of patients arrived at out patient department (OPD) late. The findings suggest that fine-needle aspiration can be used as a quick diagnostic test even in remote areas by the general practitioner who can send the slides for evaluation to a pathologist. Many times, clinically looking epidermoid cyst can reveal certain challenging entities such as a biphasic fibroepithelial tumor with cystic squamous metaplasia and proliferating pilar tumor in our series. The study of this lesion is also needed for early diagnosis as long-standing lesion may rupture and cause requirement of extensive treatment followed cosmetic impairment.

Betadine Soaking of Silicone Coupons Minimally Impacts Acellular Dermal Matrix Incorporation in a Preclinical Primate Model.

Microbial pathogens local to prosthetic breast devices may promote infection, inflammation, and capsular contracture. Although antimicrobial solutions have been used, their effects on human acellular dermal matrix (HADM) incorporation when used with prosthetic devices are unknown. The authors' objective was to histologically assess the effect of 10% povidone iodine (PI)-saturated tissue expander (TE) exposure on HADM biological response in a primate model. They hypothesized that PI exposure would not negatively affect the HADM biological response. Samples (1.5 × 1.5 cm) from smooth silicone TEs were saturated in saline or PI for 2 minutes and sutured to HADM to create HADM/TE constructs. Primates implanted subcutaneously with saline ( n = 9) and PI-treated HADM/TE ( n = 9) construct pairs were evaluated histologically for biological response after 2 or 4 weeks by means of a host response scoring scale (1 to 9), including recellularization, neovascularization, and inflammation. Inflammatory cells (eosinophils, lymphocytes, neutrophils, histiocytes, foreign-body giant cells) and evidence of HADM remodeling (fibroblasts, vessels) were further evaluated by means of a cell-specific scoring scale (0 to 4) and corroborated by immunostaining (CD3, CD20, CD68, FSP-1, collagen type IV). Mean histology scores were similar between saline- and PI-exposed HADM at 2 weeks (5.3 ± 0.9 and 5.6 ± 0.5; P = 0.52) and 4 weeks (4.6 ± 1.0 and 4.2 ± 0.9; P = 0.44). There was no difference in inflammatory cell presence at 2 and 4 weeks between groups. Fibroblast infiltration differences were insignificant between groups but exhibited trends toward an increase between time points for saline (1.6 ± 0.7 to 1.8 ± 0.8) and PI (1.3 ± 0.8 to 1.8 ± 1.0) groups, suggesting HADM incorporation over time. Data suggest that HADM exposure to PI-treated TEs does not negatively affect inflammation, vascularization, recellularization, incorporation, or host response to HADM in this model. PI is a surgical pocket irrigant used to address bacterial colonization, but its impact on ADM incorporation is unknown. This study demonstrates similar biologic response to ADMs adjacent to PI- or saline-saturated TEs in a primate model.

Cytomorphological spectrum of pilomatricoma - A series of 28 cases.

Pilomatricoma is a benign tumour that originates in the outer sheath of the hair follicle root. The clinical diagnosis of this rare entity is often missed, possibly due to a lack of awareness. Its characteristic cytomorphological features are sheets of ghost cells, basaloid cells, calcification and foreign body giant cell reaction. However, the above features may not all be present in all cases, rendering cytological diagnosis difficult. This retrospective study included all cases of pilomatricoma diagnosed on fine needle aspiration over a period of 4 years. The histopathological diagnosis was retrieved for the cases wherever possible. A detailed histopathological and cytological evaluation was performed for the various components-basaloid cells, ghost cells, calcified debris, foreign body giant cells, bare nuclei, neutrophils, and macrophages-and they were graded on a scale of 0 to 3+. The 28 cases included 8 female and 20 male patients with a mean age of 34.6 years. Most cases (22 cases; 78.6%) were located in the head and neck, with the scalp being the most common site. Twenty-five cases were cytologically diagnosed as pilomatricoma based on a variable admixture of the various components-nests of basaloid cells, ghost cells, foreign body giant cell reaction, calcified debris and viable squamous cells. However, in two cases which showed an absence of basaloid cells, a differential diagnosis of epidermal inclusion cyst was also included. Another case showed a predominance of basaloid cells with a paucity of ghost cells, so a differential diagnosis of adnexal tumour was also included. Among all the cytological parameters, sheets of ghost cells followed by nests of basaloid cells and foreign body giant cell reaction had the highest sensitivity in the cytological diagnosis of pilomatricoma. The presence of sheets of ghost cells is the most sensitive parameter for the cytological diagnosis of pilomatricoma. It is important that pilomatricoma should be considered in the differential diagnosis of subcutaneous masses, particularly in the head and neck region.

Mechanisms of Foreign Body Giant Cell Formation in Response to Implantable Biomaterials

Long term function of implantable biomaterials are determined by their integration with the host's body. Immune reactions against these implants could impair the function and integration of the implants. Some biomaterial-based implants lead to macrophage fusion and the formation of multinucleated giant cells, also known as foreign body giant cells (FBGCs). FBGCs may compromise the biomaterial performance and may lead to implant rejection and adverse events in some cases. Despite their critical role in response to implants, there is a limited understanding of cellular and molecular mechanisms involved in forming FBGCs. Here, we focused on better understanding the steps and mechanisms triggering macrophage fusion and FBGCs formation, specifically in response to biomaterials. These steps included macrophage adhesion to the biomaterial surface, fusion competency, mechanosensing and mechanotransduction-mediated migration, and the final fusion. We also described some of the key biomarkers and biomolecules involved in these steps. Understanding these steps on a molecular level would lead to enhance biomaterials design and improve their function in the context of cell transplantation, tissue engineering, and drug delivery.

Cutaneous Rhinosporidiosis Masquerading as a Soft Tissue Tumour Diagnosed on FNAC

Background: Rhinosporidiosis refers to a granulomatous inflammation of mucocutaneous sites caused by Rhinosporidium Seeberi, presenting most frequently as polypoidal lesions in the nose and nasal cavity. Involvement of sites like the conjunctiva, trachea, nasopharynx, skin, and genitourinary tract are rare. Cases of nasal rhinosporidiosis with satellite skin nodules around head and neck region has been reported. Primary cutaneous involvement is however extremely rare [1]. We report the case of a 58 year old male who came with complaints of anterior chest wall swelling since 2 months with sudden increase in size. The patient was sent for FNAC with a clinical diagnosis of a soft tissue tumor. FNAC however revealed sporangia of varying sizes with endospores along with foreign body giant cell reaction. Histopathological examination confirmed the diagnosis. Cutaneous rhinosporidiosis may mimic a soft tissue tumor. FNAC being a minimally invasive and less expensive procedure gave a definitive diagnosis, and also aided to initiate prompt management of the condition.

Idiopathic calcinosis cutis with unusual histomorphology and negative von Kossa stain: A diagnostic pitfall

Introduction: Calcinosis cutis is characterized by basophilic crystalline or amorphous calcium within the dermis/subcutis. Calcinosis cutis has many different clinical subtypes and associated etiologies that may lead clinicians to consider this diagnosis. Von Kossa and/or Alizarin red special stains may be used by pathologists to highlight deposition of insoluble calcium salts, especially in histologically ambiguous or subtle cases. Case Report: We report the case of a 27-year-old male who presented with an inferior right buttock mass clinically diagnosed as epidermal inclusion cyst(s). Gross pathology revealed a gray-white pasty substance within a cyst-like structure. Histopathologic examination demonstrated pools of amorphous blue-gray material with rare deposits of admixed coarse calcifications surrounded by foreign-body giant cells. No cyst wall was seen in the specimen. Special stains, including von Kossa, were initially negative. Following additional review, it was discovered that surface decalcifying solution had been applied to the paraffin block in the histology lab prior to microtome sectioning. Hypothesizing that this could be the cause of the unusual morphology, the paraffin block was reprocessed and subsequent H and E stained sections displayed characteristic basophilic calcium deposits, which were correspondingly positive by von Kossa stain. Conclusion: The histopathologic diagnosis of calcinosis cutis is apparent by HandE in most cases, though von Kossa and/or Alizarin red special stains can be used to aid the pathologist. Given the unusual histomorphology following surface decalcification and initial lack of von Kossa stain prior to reprocessing, this report serves to make pathologists aware of this potential diagnostic pitfall.

Triple-layered composite mesh for managing anterior abdomen wall defects in ventral hernia

Introduction: In managing ventral hernia, using mesh for the anterior abdominal wall defect closure has become a standard. Different types of materials have been used as a mesh, each with its own benefits and drawbacks. This study aimed to investigate the potential of a triple-layered composite mesh made from amniotic membrane-coated polypropylene mesh (AMPM) with an adhesion barrier as an alternative for anterior abdominal wall defect closure. Methods: An experimental study was conducted using Sprague-Dawley mice, imposed with a mechanical ventral hernia and divided into four groups with different treatments: sham surgery, mesh polypropylene, AMPM composite, and AMPM with adhesion barrier (triple-layered composite mesh). After 7 and 30 days of the procedure, the mice were evaluated for the recurrence of anterior abdominal wall defects, the histological profile of polymorphonuclear (PMN) cells, foreign body giant cells (FBGC), fibroblast cells, neovascularization, and adhesion of mesh to surrounding tissue in each group. Results: No anterior abdominal wall defect recurrence was observed in all groups at 7- and 30-days post-procedure. We found no significant difference in histological profiles of PMN, FBGC, and fibroblast cells from each group. There was a statistically significant difference in the neovascularization (p=0.025) and adhesion (p=0.034) between the polypropylene mesh group and the triple-layered composite mesh group. Conclusion: Triple-layered composite mesh has the potential to be an alternative to cover anterior abdominal wall defects, with triple-layered composite mesh and AMPM mesh groups showing a significantly higher rate of neovascularization and a lower rate of adhesion than the polypropylene mesh group.

SPTing across condensates: SEC-mediated translocation of SPT complex from pausing condensates to elongation condensates.

Several independent studies in the last few years have suggested that phase separation and biomolecular condensation play a critical role in regulating different transcription steps from initiation to pausing and elongation. However, how components of the transcription machinery translocate among different types of condensates during transcription remains poorly understood. Guo etal have now identified a potential mechanism underlying translocation of the DSIF complex from pausing to elongation condensates during promoter pause release, as reported in this issue of EMBO reports.