The Impact of COVID-19 Pandemic Restrictions on Musculoskeletal Pathology Services.

BACKGROUND AND OBJECTIVES:  The COVID-19 pandemic has had a negative impact on healthcare in musculoskeletal pathology. There is no standard protocol for pathology services during a pandemic. The study aimed to assess the impact of COVID-19 restrictions on the workload of the musculoskeletal pathology service and the hurdles faced in collaboration with the orthopedic oncology unit in a tertiary reference center in a developing country. MATERIALS AND METHODS:  The pathology reports from mid-March to mid-June 2019, 2020, and 2021 were retrospectively reviewed. RESULTS:  Significant differences were found between the pandemic period (2020) and the non-pandemic periods (2019-2021) in benign bone and soft tissue lesions, resection surgeries, and soft tissue tumors, which were more prevalent in the non-pandemic periods. However, there was no significant decrease in biopsy procedures. Conclusion: During the pandemic period, the biopsy procedure appears to be feasible for bone and soft tissue lesions without the need for anesthesia.

Chronic recurrent multifocal osteomyelitis: A multidisciplinary experience of 22 pediatric cases with a mean follow-up of 27 months.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is not a well known disorder among nonpediatricians. The aim of this study is to retrospectively evaluate the clinical outcomes of twenty-two CRMO patients presenting to two referral centres. METHODS: This retrospective study included twenty-two children (12 males, 10 females; mean age 13 years; range 7-17 years). The diagnosis was based on clinical, radiological, and pathological findings. Data were retrieved from hospital charts. RESULTS: The mean delay in diagnosis was 26 months (range, 0-96 months). The mean follow-up after diagnosis was 27.4 months (range, 6-47 months). Symptoms included pain, limping, local swelling, morning stiffness, and fever. 18 patients had multifocal and 4 patients had unifocal disease. Bone lesions were detected with whole-body or local MRI (Magnetic Resonance Imaging). The mean number of bone lesions was 2.5 (range, 1-8). Ten cases underwent biopsy to exclude malignancy and infection. Prior to diagnosis, cast immobilization or curettage was erroneously performed in four patients. One patient suffered from vertebral compression fracture. There is no growth disturbance or deformity in any patient. CONCLUSION: This study demonstrated that early recognition of the disease can be improved by using Bristol criteria which should be evaluated by a multidisciplinary team rather than one single specialist. In this way, the reliability of these criteria is improved and the treatment could be given earlier with decreased delay in diagnosis. This multidisciplinary approach is also important for decision for biopsy, timely aggressive medical treatment, and follow-up of the disease to minimise possible complications.

PD-L1 Status in Tenosynovial Giant Cell Tumors.

Background and Objectives: Tenosynovial giant cell tumors (TSGCTs) are benign soft tissue tumors that are divided into localized- and diffuse-type tumors, according to the World Health Organization classification of soft tissue tumours. The diffuse-type TSGCT sometimes behave aggressively and poses treatment challenges especially in patients with neurovascular involvement. Symptomatic patients who are not good candidates for surgery due to high morbidity risk may benefit from medical therapy. Objectives: Drugs that target programmed death ligand 1 (PD-L1) are among a new generation of medical therapy options, which, recently, have been explored and have displayed promising results in various cancer types; therefore, we aimed to investigate the PD-L1 status of TSGCTs as a possible therapeutic target. Materials and Methods: We assessed the PD-L1 status of 20 patients (15 men and 5 women, median age = 39 years) that had been diagnosed with TSGCTs in a single institution, between 2018 and 2020. The patients had localized- (n = 7) and diffuse-type (n = 13) TSGCTs. Formalin-fixed paraffin-embedded (FFPE) blocks were retrospectively retrieved from the pathology department. An immunohistochemical analysis was performed in sections of 3 micron thickness from these blocks. Results: Seventy-five percent of our patients with TSGCTs were immunopositive to PD-L1 staining. Conclusions: Taking into consideration the high positivity rate of PD-L1 staining in TSGCTs, PD-L1 blockage may be used as a valuable medical treatment for TSGCTs; however, further studies are needed.

Predictive value of KRAS/NRAS, IL-4 VNTR and HPV alterations in metastases of colorectal cancer.

PURPOSE: The main aim of the study was to evaluate the potential roles of KRAS/NRAS proto-oncogenes, IL-4 VNTR variants and HPV prevalence in colorectal cancer metastasis. As the second aim, the interactions of the analyzed genes and viral sequences with both clinicopathological variables and each other were targeted. METHODS: DNA was extracted using AmoyDx FFPE DNA Extraction kit from paraffin-embedded colorectal tumor tissue samples (n = 60). NRAS/KRAS mutational profiles were determined with real-time polymerase chain reaction using AmoyDx KRAS/NRAS Mutation Detection Kit. Genotyping of IL-4 VNTR was made with PCR. HPV detection was analyzed by PCR with both GP5+/GP6+ consensus primers and type-specific primers for HPV-16 and HPV-18. SPSS v22 (IBM) statistics software was used for all statistical analyses. RESULTS: From the demographical/clinicopathological parameters, age and biopsy specimens revealed an association with metastasis. KRAS mutation rate was as high as 65 % in the patients and the most prevalent mutation type was G12D. Metastasis risk was 3.19-fold increased in KRAS-mutated patients compared to KRAS-negative ones. IL-4 VNTR genotypes/alleles were not associated with metastasis in our analysis.  The frequency of HPVs in our colorectal cancer cohort was 36.7 %, but HPV positivity was not found to be associated with metastasis.  A significant association was found between HPV and NRAS mutations; NRAS wild-type status acted as a protective factor by 7.5-fold for HPV negativity. CONCLUSION: Our study comprehensively and concomitantly evaluated several potential molecular risk factors. Future studies designed in such combined approaches will substantially contribute to better manage colorectal cancer tumorigenesis from molecular biological perspective (Tab. 6, Fig. 2, Ref. 40).

The Effect of Platelet-Rich Fibrin and Hyaluronic Acid on Perforation of Nasal Septum.

BACKGROUND: Conservative approaches and surgical methods have been tried for the treatment of nasal septum perforations (NSPs), but a satisfactory method has not yet been determined. OBJECTIVE: Our study aimed to investigate the effect of platelet-rich fibrin (PRF) and hyaluronic acid (HA) in repairing NSPs, which were experimentally created in rabbit septum. METHODS: A total of 36 white New Zealand rabbits were included in the study. Perforations measuring 0.7 × 0.7 cm were created in their nasal septa. No additional intervention was made to the control group, which was the first group. For the second, third, and fourth groups, respectively, HA, PRF, and HA + PRF were used in the NSP region. Macroscopic and histopathological evaluations were performed after 40 days. RESULTS: In the first group, closure was observed in none of the rabbits' NSPs. In the second group, 6 rabbits (66.7%) had full closure in their NSPs. In the third group, the NSP of 6 rabbits (66.7%) was completely closed. In the fourth group, the NSP of 7 rabbits (77.8%) had full closure. CONCLUSION: Statistically significant closure was achieved with PRF and/or HA in rabbits in which NSP was established. These materials can be used to increase the likelihood of perforations closing.

Primary T-Cell Lymphoma of the Parotid Gland.

Primary malignant lymphomas of parotid gland are very rare. Most are B-cell lymphomas, and T-cell lymphomas are very rare. Unfortunately, fine needle aspiration biopsy is non-diagnostic. We, herein, present a case of a 51-year male, who presented with a large mass in the left parotid gland that had rapidly grown over a few months. As fine needle aspiration biopsy was non-diagnostic, we decided to take an incisional biopsy to disclose the pathology. The lesion was diagnosed as T-cell lymphoma after immunohistochemical examination of the specimens. Following 2-[18F] fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT), the disease was staged as 'Stage I'. The patient received six sessions of cyclophosphamide, doxorubicin, vincristine and prednisone protocol as chemotherapy management. After the completion of chemotherapy, complete remission was achieved. In suspected cases, an incisional open parotid core biopsy should be considered for a definite diagnosis. As the treatment of lymphomas is not surgical, this approach avoids a parotidectomy, which in turn, avoids facial nerve complications. Key Words: T-cell lymphoma, Parotid gland, Malignant lymphoma, Incisional biopsy, Fine needle aspiration biopsy.

Inhibitory effect of mesna and 5-fluorouracil on propylene glycol-induced cholesteatoma in rats.

OBJECTIVE: The aim of this study was to investigate the inhibitory effect of different doses of sodium-2-mercaptoethanesulphonate (MESNA) and 5-fluorouracil on cholesteatoma formation. METHODS: Fifty-six Wistar albino male rats were divided into seven groups with eight rats in each. On the first, eighth and fifteenth days, 0.2 ml of saline was administered to the group 1 (control group), and propylene glycol to induce cholesteatoma the other groups. On the 22nd day of the study, 0.2 ml saline was given to Group 1 and Group 2. Groups 3 to 7 were treated with 0.2 ml 100% MESNA, 0.2 ml 50% MESNA, 0.2 ml 20% MESNA, 0.2 ml 5-fluorouracil and 0.1 ml 100% MESNA plus 0.1 ml 5-fluorouracil, respectively, with all applications performed by intratympanic injection. RESULTS: Significant differences were found between Group 1 and all other groups except Group 3. Significant differences were also found between Group 3 and Groups 2, 5 and 6 (P < 0.05). CONCLUSIONS: According to the results of this study, experimental cholesteatoma induced with propylene glycol may be inhibited by MESNA at 100% concentration.

Prognostic and clinicopathologic value of ki-67 and profilin 1 immunohistochemical expression in primary pT1 urothelial bladder cancer.

PURPOSE: To investigate the prognostic and clinicopathologic value of Ki-67 and profilin 1 immunohistochemical expression in primary pT1 papillary urothelial bladder cancer. MATERIALS AND METHODS: This study included 88 male and 13 female pT1 primary bladder cancer patients. Demographic characteristics, tumor histological grade, tumor number, presence of concomitant carcinoma in situ, tumor size, and status of recurrence or progression were recorded for each patient. Expression of Ki-67 and profilin 1 was evaluated by immunohistochemical analysis of paraffin-embedded tumor tissues. The Pearson's Chi-square test was used for the analysis of qualitative data, and the Kaplan-Meier method and the log-rank test were used for the survival analysis. RESULTS: In the mean follow-up period of 52 months, 52 (51.5%) patients experienced recurrence, 24 (23.8%) patients experienced progression, and 17 (16.8%) patients died from bladder cancer-related causes. Ki-67 expression was significantly associated with tumor histological grade (P = 0.001). In multivariate analysis, Ki-67 positivity had significantly worse outcome for recurrence (P = 0.006) and mortality (P = 0.022). Ki-67-positive (Ki-67 index ≥15%) patients had shorter recurrence-free (P = 0.003), progression-free (P = 0.002), and cancer-specific (P = 0.003) survival. However, no statistically significant relationship was found between profilin 1 expression and clinicopathologic features and prognosis. CONCLUSIONS: Ki-67 is a highly predictive biomarker for recurrence-free, progression-free, and cancer-specific survival in pT1 bladder cancer patients, in whom prediction of recurrence and progression are difficult. Ki-67 expression can be safely combined with other prognostic factors. However, in pT1 bladder cancer patients, no significant relationship was found between profilin 1 expression and tumor characteristics or prognostic parameters.

Comparison of miRNA expressions among benign, premalignant and malignant lesions of the larynx: could they be transformation biomarkers?

BACKGROUND: The malignancy potential of the laryngeal lesions are one of the major concerns of the surgeons about choosing the treatment options, forming surgical margins, deciding the follow-up periods. Finding a biomarker to overcome these concerns are ongoing challenges and recently microRNAs (miRNAs) are attributed as possible candidates since they can regulate gene expressions in the human genome. The objective of our study was to investigate their capability as a transformation biomarker for malignant laryngeal lesions. MATERIALS AND METHODS: We investigated mature miRNA expressions in paraffin-embedded surgical specimens of human laryngeal tissues grouped as benign, premalignant or malignant (n = 10 in each). miRNA profiling was carried out by quantitative Real-Time polymerase chain reaction (RT-qPCR) and data were analyzed according to fold regulation. RESULTS: Our results demonstrated that 9 miRNAs were upregulated as the lesions become more malignant. Among them Hs_miR-183_5p, Hs_miR-155_5p, and Hs_miR-106b_3p expressions were significantly 4.16 (p = 0.032), 2.72 (p = 0.028) and 3.01 (p = 0.022) fold upregulated respectively in premalignant lesions compared to the benign lesions. Moreover, their expressions were approximately 2.76 fold higher in the malignant group than in the premalignant group compared to the benign group. Besides them, significant 7.57 (p = 0.036), 4.45 (p = 0.045) and 5.98 (p = 0.023) fold upregulations of Hs_miR-21_5p, Hs_miR-218_3p, and Hs_miR-210_3p were noticed in the malignant group but not in the premalignant group when compared to the benign group, respectively. CONCLUSION: MiRNAs might have important value to help the clinicians for their concerns about the malignancy potentials of the laryngeal lesions. Hs_miR-183_5p, Hs_miR-155_5p, and Hs_miR-106b_3p might be followed as transformation marker, whereas Hs_miR-21_5p, Hs_miR-218_3p, and Hs_miR-210_3p might be a biomarker prone to malignancy.

A Case of Inverted Papilloma Originating from the Middle Ear and Review of the Literature.

Inverted papilloma (IP) with malignant transformation is rarely seen in the middle ear. Up to now, there have been 16 primary middle ear IPs reported in the English literature. Even though it is very rare in the middle ear, this pathology should be kept in mind for the differential diagnosis of middle ear masses. In this case, we report a 77-year-old female who had recurrent IP with malignant transformation and complication.

Testis-sparing surgery of unilateral testicular large-cell calcifying Sertoli cell tumor: a sporadic case.

Testicular sex cord-stromal tumors constitute a small portion of all types of testicular tumors. Only 1% of these tumors are pure Sertoli cell tumors. Sertoli cell tumors have three identified subgroups: large-cell calcifying (LCCSCT), sclerosing Sertoli cell and general type. Up to 40% of LCCSCT are associated with the genetic syndromes like Carney complex, Peutz-Jeghers syndrome. These lesions are usually benign, only 17% of the cases show malignant behaviour. Herein, we report a case of unilateral LCCSCT in a 37 year-old man without any hormonal symptoms or inherited diseases which was succesfully treated with testis-sparing surgery.

Grinspan's Syndrome: A Rare Case with Malignant Transformation.

AIM: Oral lichen planus (OLP) is one of the common chronic inflammatory, noninfectious, and precancerous oral mucosal diseases that affect the stratified squamous epithelium in adults. Grinspan et al. reported an association of OLP with diabetes mellitus and vascular hypertension and called that Grinspan's syndrome in 1966. We aim to present a case of Grinspan's syndrome with malignant transformation. CASE PRESENTATION: A 60-year-old man who presented with a ten-year history of OLP diagnosed clinically and histologically was referred to our otolaryngology department with a painless swallowing in the left buccal mucosa for 3 months. Clinical examination revealed several plaques, striated white lesions in the buccal mucosa bilaterally, and an exophytic tumor in the left buccal mucosa. Histopathological examination showed lichen planus bilaterally and oral squamous cell carcinoma in the left buccal mucosa. The tumor had been developed on the preexisting areas of lichen planus which had been histologically proven before. The tumor was removed completely, and the tissue defect on the buccal mucosa was repaired with a split-thickness skin graft. CONCLUSION: Patients with OLP should be followed up periodically in a long term at close intervals for early diagnosis of malignant transformation.

Nasopharyngeal Pleomorphic Adenoma: A Rare Case Report and Review of the Literature.

Salivary gland tumors are rare among all head and neck tumors. Pleomorphic adenoma (PA) is the most commonly seen subtype, and 85% of the cases are located in the parotid gland. PA may very rarely be seen in minor salivary glands. Minor salivary gland PAs are mostly located in the hard and soft palates. Nasopharyngeal PA is very rare, and a total of 8 cases have been published to date. In this case report, a 51-year-old female patient who had nasopharyngeal PA with chondroid metaplasia is presented, and we review the relevant literature.

Papillary Thyroid Microcarcinoma with a Large Cystic Dilated Lymph Node Metastasis to the Neck Mimicking a Branchial Cleft Cyst: A Potential Pitfall.

Lateral cervical cystic mass in a young adult very rarely could be a first sign of an occult thyroid papillary microcarcinoma metastasis. In this paper, we presented a 37-year-old male patient whose preoperative 6 cm left lateral cervical cystic mass was initially diagnosed as branchial cleft cyst, but then the postoperative histopathological examination of the mass was revealed as papillary thyroid carcinoma metastasis. Preoperative fine needle aspiration biopsy was relevant with a branchial cleft cyst. In the left thyroid lobe there were 3 solid nodules with 4, 6, and 12 mm dimensions, respectively. One of the nodules had malignant well-differentiated cells diagnosed after fine needle aspiration biopsy. After total thyroidectomy, histopathologic evaluation of biopsy material's showed papillary thyroid microcarcinomas. This case indicates that especially in a young adult lateral cervical cystic mass should be carefully considered preoperatively for the possibility of metastatic occult thyroid carcinoma, especially for papillary carcinoma in differential diagnosis, and evaluation of the thyroid gland should be taken into account.

Three years of retrospective evaluation of skin biopsy results in childhood.

OBJECTIVE: In our study, we aimed to evaluate retrospectively histopathological diagnoses of children based on their skin biopsies, and determine the prevalence of the disease in question. METHODS: Among patients who applied to Medeniyet University Goztepe Training and Research Hospital between January 2011 and February 2014, we retrospectively evaluated demographic data and histopathological diagnoses of patients aged between 0-17 years whose skin punch biopsy samples were obtained. RESULTS: The study population (n=566) with skin biopsy results consisted of 287 (50.7%) male, and 279 (49.2%) female patients with a mean age of 10.04±4.84 years. Biopsy materials were obtained from the various age groups as follows: 0-2 years, n=31 (5.4%); 3-5 years, n=67 (11.8%) 6-11 years, n=165 (29.1%), and 12-17 years, n=303 (53.5%). Among all age groups, we took biopsies mostly from patients with noninfectious erythematous squamous (24%) and vascular (21.2%) diseases. The determined histopathological diagnoses were leukocytoclasis vasculitis (18.9%), psoriasis (7.4%), melanocytic nevus (5.4%), and contact dermatitis (5.1%) respectively. CONCLUSION: We determined that skin punch biopsy examinations were done most frequently during adolescence and are mostly necessary for diagnosis of erythematous squamous and vascular diseases. If clinical evidence-based prevalence studies are supported with histopathological data, more significant results can be obtained.

A comparative study of histopathological findings in skin biopsies from patients with psoriasis before and after treatment with acitretin, methotrexate and phototherapy.

INTRODUCTION: Psoriasis is a chronic and inflammatory skin disease. Few studies in the literature evaluate the responses to the treatment histopathologically. OBJECTIVES: In this study, we evaluated and compared skin biopsies taken from patients with psoriasis before and after phototherapy and therapy with acitretin and methotrexate. MATERIAL AND METHODS: We included 64 patients with a diagnosis of psoriasis vulgaris in our study. We performed phototherapy on 33 patients (51.6%), while 19 patients (29.7%) were treated with methotrexate and 12 patients (18.8%) were treated with acitretin. RESULTS: All of the patients had chronic plaque psoriasis, and they had skin lesions on more than 10% of their total body surface area and a score of PASI of 7.2-21.8 (average: 12.2). The histopathological parameter scores were similar in the initial evaluations of the pre-treatment treatment groups. When the biopsy specimens of all cases were evaluated together, a significant decrease was observed in terms of parakeratosis, Munro's microabscesses, regular acanthosis, pustules of Kogoj, lymphocyte infiltration in the papillary dermis, loss of the granular layer, spongiosis, suprapapillary thinning, vascularity in the papillary dermis and neutrophile infiltration in the papillary dermis. CONCLUSION: We found in our study that conventional treatment modalities provided histopathologically significant recovery in psoriasis, but they did not have an effect on some histopathological findings. To our knowledge, it is one of the few studies to assess these parameters in psoriasis under the continuous effect of acitretin, methotrexate and phototherapy for three months. There is a need for studies with larger series to examine the histopathological effects of these treatment modalities in terms of immunopathology.

Gleason score at the margin can predict biochemical recurrence after radical prostatectomy, in addition to preoperative PSA and surgical margin status.

BACKGROUND/AIM: To evaluate the relation between biochemical recurrence (BCR) of prostate cancer and the extent of positive surgical margins (PSMs), Gleason score (GS) of the tumor at the margins, and preoperative prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: A total of 94 patients who underwent radical prostatectomy were recruited for this study and received postoperative follow-up care for 2 years. All specimens were evaluated for surgical margin status, PSM length, GS at positive margin, size of tumor, multifocality, invasion of seminal vesicle, lymphovascular invasion, and perineural invasion. PSM was defined as a prostate tumor. RESULTS: Out of 94 patients, 34 patients (36.2%) had PSMs and 46 patients (48.9%) had BCR. A statistically significant relation between having a high risk of BCR of prostate cancer and having high preoperative PSA levels (P < 0.001), PSMs (P < 0.001), or a high GS at the surgical margin (P = 0.024) was found. CONCLUSION: High preoperative PSA levels, PSMs, and tumors with high GS at the margins have a poor prognostic impact, and they correlate with a higher rate of BCR. Close follow-up of patients with PSMs with high GS and high levels of preoperative PSA is recommended.