[A clinical case of piloleiomyoma]. / Klinicheskii sluchai piloleiomiomy.

The article describes a clinical case of a benign tumor from smooth muscle cells - piloleiomyoma. The incidence of leiomyoma in the skin is 3-5% of all leiomyomas. A 27-year-old patient applied to a medical institution with complaints about an intradermal formation in the ear region that occurred repeatedly within 5 months after surgical treatment. After the first surgical intervention, the patient was consulted in various medical organizations, where the following diagnoses were made: «nodular fasciitis¼, «smooth muscle tumor without signs of malignancy¼ and «non-epithelial spindle cell neoplasm¼. According to ultrasound examination, the formation with dimensions of 11×9×5 mm reached the mastoid process of the temporal bone and was characterized by increased internal blood flow. After surgical removal of the neoplasm, taking into account the difficulties of differential diagnosis, an immunohistochemical study was conducted. An accumulation of smooth muscle cells was detected in the surface layers of the dermis under the epidermis by the immunohistochemical study with the use of the marker SMA. A study on CD34 protein revealed a high density of blood capillaries and the absence of its expression in smooth muscle cells. The proliferative index (Ki-67) and mitotic activity (PHH-3) of cells was also studied. The index of proliferative activity was less than 2%, mitoses were isolated. Thus, the results of immunohistochemical study proved the conclusion of piloleiomyoma.

Nodular fasciitis: a comprehensive, time-correlated investigation of 17 cases.

The self-limited nature of nodular fasciitis (NF) is well-known but its precise mechanism has not yet been clarified. We observed that "young" NF (preoperative duration <1 month) consistently contains a higher percentage (~80%) of USP6 break-apart FISH signals than "old" NF (preoperative duration >3 months) (~20%). Thus, we hypothesized that our original observation may reflect a connection with the self-limited nature of NF. Seventeen cases with reliable data concerning the onset were selected, thus approximating the lifetime of each tumor. Besides the USP6 interphase FISH examination, we also checked the most common MYH9-USP6 fusion using RT-PCR. Because of the known pathways of the tumorigenesis of NF, the mRNA level of USP6, TRAIL, IFN-beta, JAK1, STAT1, STAT3, JUN, and CDKN2A was measured using qRT-PCR. Regarding proteins, USP6, p16, p27, TRAIL, and IFN-beta were examined using immunohistochemistry. Targeted gene panel next-generation sequencing (NGS) of three cases was additionally performed. We found a strong negative correlation (p = 0.000) between the lifetime and percentage of USP6 break-apart signals and a strong positive relationship (p = 0.000) between USP6 break-apart signals and mitotic counts. Results of immunostainings, along with qRT-PCR results, favored the previously-suggested USP6-induced negative feedback mechanism through activation of TRAIL and IFN-beta, likely resulting in apoptosis and senescence of tumor cells harboring USP6 fusions. Targeted-NGS resulted in the detection of several variants, but no additional recurrent changes in the pathogenesis of these tumors. We revealed on a cellular level the USP6-induced negative feedback mechanism. In conclusion, we emphasize that in "old" NF, the percentage of USP6 break-apart FISH signals can be as low as 14-27% which can be very important from a differential diagnostic point of view. We emphasize that a careful examination and interpretation of the NGS data is needed before clinical decision-making on treatment.

Low 68Ga-PSMA PET/CT Uptake in Chronic Intramuscular Nodular Fasciitis.

Nodular fasciitis is an uncommon benign mass-forming myofibroblastic proliferation, most frequently found in the upper limbs, with only rare intramuscular cases. We describe herein a case of chronic nodular fasciitis of the left triceps muscle with a low Ga-labeled prostate-specific membrane antigen (PSMA) ligand uptake on PET/CT. Ga-PSMA ligands bind to PSMA-expressing prostate cancer cells, but uptake has also been demonstrated in other solid neoplasms and various benign lesions. Nodular fasciitis should be included in the differential diagnosis of soft tissue lesions with variable Ga-PSMA uptake.

Nodular fasciitis, a forgotten entity.

BACKGROUND: Nodular fasciitis is a benign pseudosarcomatous, self-limited, and reactive process. Based on its clinical and histological features - a fast-growing, solitary tumor with high cellularity and mitotic count - nodular fasciitis is considered to be a benign mimic of sarcoma. METHODS: We present four cases of nodular fasciitis and a review of the literature. RESULTS: The cases we present were initially misdiagnosed as sarcoma; two as dermatofibrosarcoma protuberans, one as atypical fibroxanthoma, and one as leiomyosarcoma. CONCLUSION: Awareness of this entity among dermatologists is important as misdiagnosis may lead to unnecessary treatments associated with increased morbidity.

Papillary thyroid carcinoma with desmoid-type fibromatosis: A clinical, pathological, and immunohistochemical study of 14 cases.

Papillary thyroid carcinoma (PTC) with desmoid-type fibromatosis (DTF) is characterized by genetic alterations of the fibroblasts. PTC-DTF is extremely rare, and the reports on such cases have been sporadic. Immunohistochemical staining using the antibody for beta-catenin is useful in diagnosing the variant. This report aims to describe the clinical, pathological, and immunohistochemical findings in 14 cases of PTC-DTF and to clarify the diagnostic significance of the variant. The patients included 9 women and 5 men, with a mean age of 49.3 years. PTCs with focal DTF components and with extensive DTF components included 7 cases each. No significant differences were noted in terms of age, gender, and serum thyroglobulin levels between extensive and focal DTF cases. On aspiration cytology, 12 cases were reported as suspicious for malignancy or malignant, and schwannoma or fibroma was suggested in 1 case each. The DTF components were histologically classified into 4 types, namely, central (4 cases), peripheral (1 case), mixed (7 cases), and diffuse type (2 cases). The stromal components were consistent with those of DTF. Immunohistochemically, fibroblasts in the DTF components showed nuclear and cytoplasmic expression for beta-catenin in 12 cases. The features are observed even in cases in which stromal components focally exist. Neither carcinoma cells nor the fibroblasts with Ki-67 labeling index >5% were found in all cases. We agree that PTC with nodular fasciitis-like stroma should be renamed to PTC-DTF.

Cerebral 18F-FDG PET in macrophagic myofasciitis: An individual SVM-based approach.

INTRODUCTION: Macrophagic myofasciitis (MMF) is an emerging condition with highly specific myopathological alterations. A peculiar spatial pattern of a cerebral glucose hypometabolism involving occipito-temporal cortex and cerebellum have been reported in patients with MMF; however, the full pattern is not systematically present in routine interpretation of scans, and with varying degrees of severity depending on the cognitive profile of patients. Aim was to generate and evaluate a support vector machine (SVM) procedure to classify patients between healthy or MMF 18F-FDG brain profiles. METHODS: 18F-FDG PET brain images of 119 patients with MMF and 64 healthy subjects were retrospectively analyzed. The whole-population was divided into two groups; a training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy subjects). Dimensionality reduction was performed using a t-map from statistical parametric mapping (SPM) and a SVM with a linear kernel was trained on the training set. To evaluate the performance of the SVM classifier, values of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were calculated. RESULTS: The SPM12 analysis on the training set exhibited the already reported hypometabolism pattern involving occipito-temporal and fronto-parietal cortices, limbic system and cerebellum. The SVM procedure, based on the t-test mask generated from the training set, correctly classified MMF patients of the testing set with following Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%. CONCLUSION: We developed an original and individual approach including a SVM to classify patients between healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning algorithms are promising for computer-aided diagnosis but will need further validation in prospective cohorts.

HIF-1α, MDM2, CDK4, and p16 expression in ischemic fasciitis, focusing on its ischemic condition.

Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene. Seven cases of ischemic fasciitis from among the soft-tissue tumors registered at our institution were retrieved. Histopathological findings were as follows: poorly demarcated nodular masses, a proliferation of spindle-shaped fibroblastic or myofibroblastic cells with oval nuclei and eosinophilic or pale cytoplasm, zonal fibrinous deposition, pseudocystic degeneration, granulation-like proliferation of capillary vessels, ganglion-like cells, myxoid or hyalinized stroma, and chronic inflammatory infiltration. Immunohistochemically, the spindle cells were positive for HIF-1α (7/7 cases), MDM2 (4/7 cases), CDK4 (4/7 cases), p16 (7/7 cases), p53 (2/7 case), cyclin D1 (7/7 cases), and alpha-smooth muscle actin (6/7 cases). Neither MDM2 gene amplification nor USP6 gene split signal was detected in any case. Overexpression of the above proteins may be associated with the pathogenic mechanism of ischemic fasciitis. It is noted that the immunohistochemical positivity of MDM2, CDK4, and p16 do not necessarily indicate malignant neoplasm such as dedifferentiated liposarcoma.

Morin Stain Detects Aluminum-Containing Macrophages in Macrophagic Myofasciitis and Vaccination Granuloma With High Sensitivity and Specificity.

Macrophagic myofasciitis (MMF) is an inflammatory condition associated with the intramuscular (i.m.) injection of aluminum adjuvant-containing vaccines. It is clinically characterized by myalgia, weakness, and chronic fatigue and histologically by aggregates of cohesive macrophages with abundant basophilic, periodic acid-Schiff (PAS)-positive, diastase-resistant granules that percolate through the peri- and endomysium without eliciting substantial myofiber damage. The definitive diagnosis of MMF requires demonstration of aluminum within these macrophages. We evaluated the Morin stain, a simple, 2-step histochemical stain for aluminum, as a confirmatory diagnostic tool for MMF. Among 2270 muscle biopsies processed at UTSW between 2010 and 2015, a total of 12 MMF cases and 1 subcutaneous vaccination granuloma case were identified (11 pediatric, 2 adults). With the Morin stain, all 13 cases showed strong granular reactivity within the cytoplasm of macrophages but not in myofibers or connective tissue. Three cases of inflammatory myopathy with abundant macrophages (IMAM), 8 cases of granulomatous inflammation and 23 other deltoid muscle biopsies used as controls were all negative. Morin stain could be used in both formalin-fixed paraffin-embedded and cryostat sections. Thus, Morin stain detects aluminum with high sensitivity and specificity in human muscle and soft tissue and may improve the diagnostic yield of MMF and vaccination granuloma.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18F-FDG. Methods:18F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment (n = 42), those with frontal subcortical (FSC) dysfunction (n = 29), those with Papez circuit dysfunction (n = 22), and those with callosal disconnection (n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism (P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction.

68Ga-PSMA PET/MR Showing Intense PSMA Uptake in Nodular Fasciitis Mimicking Prostate Cancer Metastasis.

The recently introduced PSMA PET has developed as a powerful imaging tool for staging of prostate cancer. This case showed an intense uptake of Ga-PSMA in a soft-tissue mass of the rectus femoris muscle. Histopathology revealed the diagnosis of fasciitis nodularis. Therefore, it advises caution particularly in patients with solitary and atypical located lesions as they might not be indicative for metastatic prostate cancer, but eventually be caused by different conditions.

[Applying HIFU for the obliteration of the veins in the experiment ].

The effect of high-intensity focused ultrasound (HIFU) on venous wall structure was studied in the rabbit model. Special setup was developed for ultrasound generation and vessel targeting. Methods. The essential part of the setup is spherical focusing power irradiator with following characteristics: power supply voltage of 25 V, frequency of 1.9 MHz, ultrasound intensity in the focal spot ~8.7 kW/cm2. Results. Single 15-s exposure of the femoral vein to HIFU resulted in partial desquamation of the endothelium, vacuolization of myocyte cytoplasm, misarrangement and coagulation of collagen fibers. Pulsed HIFU (5 pulses for 5 s each) caused protein coagulation in all layers of venous wall (v. cava posterior) as well as the appearance of the areas of fibrinoid necrosis, severe endothelial desquamation, and intimal detachment. HIFU-induced collagen structural changes in media and adventitia of the vein suggest that HIFU exposure resulted in local temperature increase up to ~60°Ð¡. In some experiments, adjacent to the vein muscles were also exposed to HIFU. In this case, edema of the interstitium and muscle fibers was registered, as well as fragmentation and coagulation of some fibers, altered staining patterns and neutrophil infiltration. These changes could be attributed to the development of acute muscle injury (acute fasciitis). Perivascular adipose tissue also demonstrated edema and lipolysis, red blood cell diapedesis, and leukocyte infiltration. Conclusion. The observations on structural changes in the venous wall after HIFU exposure could lay the ground for future experiments on HIFU - mediated obliteration.

Articular nodular fasciitis of the right shoulder joint: report of an unusual case with focus on immunohistochemical differential diagnosis.

The mesenchymal lesion nodular fasciitis (NF) can affect various sites of the body but usually arises in subcutaneous tissue or occasionally skeletal muscle. NF is not commonly known to arise in joints, and articular NF is extremely rare. Herein, we present a case of a 54-year-old woman with articular NF. No sign of recurrence was observed after surgical piecemeal removal with a suspected positive surgical margin. In our case, a differential diagnosis of NF, desmoid-type fibromatosis, and low-grade myofibroblastic sarcoma was considered. Stromal hyalinization, a characteristic of articular NF, made the diagnosis somewhat difficult, although typical NF morphology was present. Immunohistochemical analysis of α-smooth muscle actin, desmin, ß-catenin, and protein gene product 9.5 expression along with close morphological examination provided a reliable distinction.

Proliferative fasciitis in the abdominal region.

A 30-year old man with no trauma history presented to our department of dermatology with a 2-year history of abdominal painful masses. The spontaneous pain and tenderness in the abdominal region gradually worsened. Physical examination revealed 3 firm, irregular subcutaneous nodules measuring 1 x 0.5 cm, which were movable and unattached to the overlying skin. One of the nodules was ulcerated (Figure 1). Histopathologic examination showed spindle-shaped fibroblast cells intermingled with gangliocyte-like giant cells in the hypodermis with an infiltrate made of lymphocytes and histiocytes (Figure 2 and Figure 3). The immunohistochemical staining showed the negativity of the fusiform cells and the gangliocyte-like cells to anti-S100 protein and to anti-smooth muscle actin.

A report of three cases of pediatric proliferative fasciitis.

Proliferative fasciitis is a rapidly growing myofibroblastic proliferation that more commonly presents in adults as a subcutaneous mass. Cases in children can cause diagnostic difficulty, as histological features often differ from classic proliferative fasciitis. We present three cases of pediatric proliferative fasciitis, in children age 5-7. Case 1 involved the subcutis and resembled conventional proliferative fasciitis. The lesion was focally positive for desmin. Case 2 involved the subcutis and was more cellular with focal sheet-like areas of ganglion-like fibroblasts. Case 3 involved the dermis and subcutis with a diffuse, solid sheet-like pattern of ganglion-like myofibroblasts with numerous mitotic figures (4 per 10 high power fields), necrosis and foci of acute inflammation. This case had a circumscribed pushing border rather than the more common infiltrating border seen in proliferative fasciitis. The cells were positive for desmin but negative for cytokeratin and had retained SMARCB1 expression. Proliferative fasciitis in childhood can have a varied histological appearance that can cause confusion with malignancies. Awareness of these histological pitfalls is critical to avoid potentially serious diagnostic errors.

Intravascular fasciitis involving the flank of a 21-year-old female: a case report and review of the literature.

BACKGROUND: Intravascular fasciitis is an uncommon variant of nodular fasciitis, which is a reactive proliferative lesion of myofibroblasts. Since its identification in 1981, only 32 cases of intravascular fasciitis have been reported in the English literature. The lesion is commonly located in the head, neck, and extremities, with only three cases arising from the trunk. Here we report the fourth case involving the trunk (the flank area). CASE PRESENTATION: A 21-year-old African-American female presented with a subcutaneous mass on her flank. Grossly, the mass was red-tan, oval, and well-demarcated, measuring approximately 0.5 cm in diameter. Microscopically, the mass was composed of spindle cells arranged in a swirling and intersecting pattern inside the lumens of two blood vessels. It extended through the vascular walls into the surrounding fibroadipose tissue; in some sections, the spindle cells were intermixed with the perivascular fibrous tissue. Elastin stain revealed remnants of elastic lamina partially surrounding the lesion. The nuclei of the spindle cells were relatively uniform with tapered ends and prominent nucleoli. No significant mitotic activity was observed. Multinucleated giant cells were scattered among the spindle cells, along with infiltrating lymphocytes and extravasated red blood cells. Immunohistochemical stains showed the spindle cells were positive for smooth muscle actin, focally positive for muscle specific actin, and negative for S-100, confirming their myofibroblastic differentiation. The overall morphological and immunohistochemical features are consistent with intravascular fasciitis. CONCLUSION: By reporting this rare case, we would like to raise the awareness of this non-neoplastic lesion to avoid misdiagnosing it as a sarcoma with vascular invasion. Previously reported similar cases were also reviewed and compared with this case.

A huge nodular fasciitis in parapharygneal space in a 7-year-old girl: a case report and review of literature.

Nodular fasciitis (NF) is a benign and reactive fibroblastic growth extending from the superficial fascia into the subcutaneous tissue or muscle, with a morbidity of less than 20% in children. We report a case of a 7-year-old girl presented with a 3-month history of snore and mouth breathing. Image findings demonstrated a large soft-tissue mass in the right parapharyngeal space. The lesion was successfully eradicated by surgical removal. Pathological analysis established NF as the final diagnosis. Histopathological findings were notable for a reactive spindle-cell process composed of proliferative fibroblasts with extravasated red blood cells and interstitial edema. Immunohistochemical stains showed that the lesional cells were positive for smooth muscle actin (SMA), muscle-specific actin (HHF35), and epithelial membrane antigen (EMA), and negative for S100 protein. No clinical evidence of recurrence was noticed after 2 months of follow-up. Being the first report of NF in the parapharyngeal space of a child, this rare pediatric case points out the importance for otolaryngologists to keep NF in mind for differential diagnosis to avoid unnecessary wide resection.

Podoplanin (D2-40) is a reliable marker of urinary bladder myofibroblasts (telocytes).

Podoplanin, D2-40, has been described in a variety of normal and neoplastic tissues. It is often used for highlighting lymphatics. We evaluated the expression of podoplanin in α-smooth muscle actinpositive myofibroblasts producing the suburothelial layer in tunica propria of the urinary bladder that have some similar features with telocytes. Our results showed that these cells demonstrate distinct D2-40 immunoreactivity from telocytes occurring in the renal pelvis and ureter. We observed positive reaction not only in bioptic specimens from women with interstitial cystitis, but also in a control group of women and men treated for pathological bladder lesion different from interstitial cystitis. It is interesting that identical staining reaction was observed in the ureters only exceptionally. In addition, we examined samples from myofibroblastic tumoriform lesions of soft tissue such as nodular fascitis and fibromatosis (desmoid) and we obtained negative results. It means that the so-called myofibroblasts of urinary bladder tunica propria have a unique immunophenotype that has probably not been described until now. Our findings suggest that D2-40 can be used as a complementary immunostainer to α-smooth muscle actin on urinary bladder biopsies from patients with interstitial cystitis. The role of D2-40 as an immunohistochemical marker is still being investigated.

Variable Ki67 proliferative index in 65 cases of nodular fasciitis, compared with fibrosarcoma and fibromatosis.

Nodular fasciitis is the most common pseudosarcomatous lesion of soft tissue. Ki67 was considered as a useful marker for distinguishing some benign and malignant lesions. To study the usefulness of Ki67 in diagnosis of nodular fasciitis, the expression of Ki67 was examined by using immunostaining in 65 nodular fasciitis specimens, 15 desmoid fibromatosis specimens and 20 fibrosarcoma specimens. The results showed that there was a variable Ki67 index in all 65 cases of nodular fasciitis, and the mean labeling index was 23.71±15.01%. In majority (70.77%) of all cases,the index was ranged from 10% to 50%, in 6.15% (4/65) of cases the higher Ki67 index (over 50%) could be seen. The Ki67 proliferative index was closely related to duration of lesion, but not to age distribution, lesion size, sites of lesions and gender. Moreover, the mean proliferative index in desmoid fibromatosis and fibrosarcoma was 3.20±1.26% and 26.15±3.30% respectively. The mean Ki67 index of nodular fasciitis was not significantly lower than fibrosarcoma, but higher than desmoid fibromatosis. The variable and high Ki67 index in nodular fasciitis may pose a diagnostic challenge. We should not misdiagnose nodular fasciitis as a sarcoma because of its high Ki67 index. The recurrence of nodular fasciitis is rare; and the utility of Ki67 immunostaining may be not suitable for recurrence assessment in nodular fasciitis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4782335818876666.