Constitutional mismatch repair deficiency syndrome with atypical features caused by a homozygous MLH1 missense variant (c.1918C>A, p.(Pro640Thr)): a case report.

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive genetic disorder caused by biallelic germline mutations in one of the mismatch repair genes. Carriers are at exceptionally high risk for developing, typically in early life, hematological and brain malignancies, as well as cancers observed in Lynch syndrome. We report a homozygous MLH1 missense variant (c.1918C>A p.(Pro640Thr)) in a Tunisian patient with CMMRD syndrome and a family history of early-age colorectal cancer. The proband presented initially with colonic oligopolyposis and adenosquamous carcinoma of the caecum. He later developed several malignancies, including undifferentiated carcinoma of the parotid, grade 4 IDH-mutant astrocytoma, and ampulla of Vater adenocarcinoma. The patient was older than typical for this disease and had a remarkably prolonged survival despite developing four distinct aggressive malignancies. The current report highlights the challenges in assessing the pathogenicity of the identified variant and the remarkable phenotypic diversity in CMMRD.

PIK3CA mutations in breast cancer: A Tunisian series.

BACKGROUND: The aim of this study was to analyze PIK3CA mutations in exons 9 and 20 in breast cancers (BCs) and their association with clinicopathological characteristics. METHODS: Mutational analysis of PIK3CA exon 9 and 20 was performed by Sanger sequencing in 54 primary BCs of Tunisian women. The associations of PIK3CA mutations with clinicopathological characteristics were analyzed. RESULTS: Fifteen exon 9 and exon 20 PIK3CA variants were identified in 33/54 cases (61%). PIK3CA mutations including pathogenic (class 5/Tier I) or likely pathogenic (class 4/Tier II) occurred in 24/54 cases (44%): 17/24 cases (71%) in exon 9, 5/24 cases (21%) in exon 20 and 2/24 cases (8%) in both exons. Of these 24 cases, 18 (75%) carried at least one of the three hot spot mutations: E545K (in 8 cases), H1047R (in 4 cases), E542K (in 3 cases), E545K/E542K (in one case), E545K/H1047R (in one case) and P539R/H1047R (in one case). Pathogenic PIK3CA mutations were associated with negative lymph node status (p = 0.027). Age distribution, histological SBR tumor grading, estrogen and progesterone receptors, human epidermal growth factor receptor 2, and molecular classification were not correlated with PIK3CA mutations (p > 0.05). CONCLUSION: The frequency of somatic PIK3CA mutations in BCs of Tunisian women is slightly higher than that of BCs of Caucasian women and more observed in exon 9 than in exon 20. PIK3CA mutated status is associated with negative lymph node status. These data need to be confirmed in larger series.

Pathologically confirmed women's breast cancer: A descriptive study of Tunisian and Algerian series.

BACKGROUND: Breast cancer (BC) is the most frequent malignancy among women in Tunisia and Algeria. Clinical and pathological characteristics of this cancer among these populations are not widely reported. The aim of the study was to report clinical and pathological characteristics of women's BC in a Tunisian and Algerian series. METHODS: Pathologically confirmed 1089 BCs were gathered in the pathology departments of three Northern Tunisian hospitals: Tunis military, Charles Nicolle and Jendouba and in the pathology department of Alger Douera hospital between January 2015 and December 2020. Clinical and pathological findings of the two series: age, tumor size, histological type, grading according to Scarff-Bloom Richardson grading system, lymph node status at the time of diagnosis in axillary lymphadenectomy specimens and the immunohistochemical expression of estrogen and progesterone receptors (ER/PR), HER2 and Ki-67, were collected from the pathological reports. RESULTS: The median age at diagnosis was 50 and 48 years in Tunisian and Algerian series, respectively (p = 0.016). The diagnosis of BC was made on surgical specimens (lumpectomy or mastectomy) in 373/491 (76%) cases of the Tunisian series and in 225/598 (37.6%) cases of the Algerian one. Median tumor size was 2.8 cm and 2.5 cm in Algerian and Tunisian series, respectively (p = 0.252). Invasive BCs not otherwise specified was observed in 440/481 (91.5%) BCs in Tunisian series and in 519/586 (88.6%) BCs in Algerian series. Axillary lymph node positive tumors were observed in 64.6% and 58.8% of Tunisian and Algerian women, respectively (p = 0.926). BCs were ER positive in 311/385 (80.8%) and 486/571 (85.1%) cases and HER2 positive in 86/283 (30.4%) and 60/385 (15.6%) cases of Tunisian and Algerian series, respectively. CONCLUSIONS: In Tunisia and Algeria, BC has poor prognostic factors with large tumor sizes and high rates of lymph nodes involvement at diagnosis.

A rare case report of sacral epidural angiolipoma: Diagnosis and treatment.

BACKGROUND: Spinal angiolipomas are rare benign tumors composed of mature adipose tissue and anomalous vascular channels. The sacral localization is extremely rare. To the best of our knowledge, there have been only two cases reported in the literature. Herein, we present an additional case of sacral angiolipoma. CASE DESCRIPTION: We present a case of a 54-year-old woman who presented with the right lumbosciatica and distal crural weakness. Spinal MRI showed an epidural lesion at the level of L5-S1 extending to the first right sacral foramen. The patient had total resection of the tumor and the histological study concluded to an angiolipoma. The patients' neurologic symptoms improved postoperatively and follow-up revealed no signs of tumor recurrence. CONCLUSION: Despite the rarity of sacral localization in angiolipomas, it is a diagnosis to be considered in the case of an epidural tumor with foraminal extension. Magnetic resonance imaging is important for detecting and characterizing spinal angiolipomas despite diagnosis is not always obvious. After surgical removal, the functional prognosis is generally favorable.

New-onset guttate psoriasis secondary to COVID-19.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is associated with flares of psoriasis in patients with well-documented disease. Both viral infection and medications used for treatment, like hydroxychloroquine, were incriminated. Herein, we report the case of a 25-year-old male patient who presented a first-onset guttate psoriasis following a COVID-19 infection. We have not found previous descriptions of de novo guttate psoriasis post-COVID-19.

Multiple endocrine neoplasia type 1 revealed by a hip pathologic fracture.

Multiple endocrine neoplasia type 1 is a rare autosomal inherited syndrome that affects a variety of endocrine tissues such as the parathyroid, endocrine pancreas, and anterior pituitary. Osseous complications are often misdiagnosed. We presented a case of a 46-year-old woman with pathological fractures of the lower limb. She had a history of type 1 diabetes and galactorrhea. Laboratory examinations showed hypercalcemia and an increased level of parathyroid hormone related to hyperparathyroidism. Serum chromogranin A level was increased at 9369 ng/mL (N < 102). A somatostatin receptor scintigraphy (octreoscan) revealed pathological uptake in the gastric wall, later cave adenopathy, and liver. The diagnosis of multiple endocrine neoplasia type 1 was made based on radiological and histological findings. The patient underwent a subtotal parathyroidectomy associated with somatostatin analog treatment leading to significant improvement. A literature review was conducted by searching PubMed using these following terms: multiple endocrine neoplasia type 1, hyperparathyroidism, fracture, menin, osteoporosis. We emphasized bone involvement related to multiple endocrine neoplasia type 1 syndrome. This diagnosis should be considered when pathological fractures occur in young patients with a history of endocrine disorder. We highlighted the importance of imaging features in making the diagnosis of multiple endocrine neoplasia type 1. Early management of this disease is necessary. Treatment including parathyroidectomy and somatostatin analogs leads to bone preservation and functional improvement.

Hemorrhagic synovial cyst: An unexpected cause of acute cervical spinal cord compression. Case report.

INTRODUCTION: Cervical synovial cysts are uncommon. They are most often responsible for a chronic clinical picture. Rarely, intracystic hemorrhage occurs, and may acutely present as radicular - or even spinal cord compression syndrome leading to irreversible neurological impairment. CASE: We reported a case of bleeding synovial cyst located in the cervico-thoracic spine causing spastic paraparesis in a 68-year-old male patient. MRI revealed narrowing of perimedullary subarachnoid space by a well circumscribed, extra-axial, homogeneous mass located posterolaterally to the right of the spinal cord at the level C7-T1. The cyst was removed thoroughly by laminectomy. Pathological findings were consistent with the diagnosis of hemorrhagic synovial cyst. The patient had an excellent recovery. DISCUSSION: Synovial cysts of the spine are rare and usually asymptomatic. It is extremely rare for intracystic bleeding to occur and be responsible for an abrupt presentation. Diagnosis of spinal synovial cyst relies on MRI but may not be evident as it depends on consistency and density of the cystic fluid. Surgery remains the best therapeutic alternative, especially in the case of neurological impairment. CONCLUSION: Surgery should be considered for any cervical synovial cyst. This is motivated by the risk, although rare, of bleeding and the resulting irreversible neurological damage that may occur.

Transformation of a prostatic adenocarcinoma into squamous cell carcinoma after luteinizing hormone-releasing hormone (LHRH) agonist and radiotherapy treatment.

Squamous cell carcinoma of the prostate is rare and represents 0.5% to 1% of prostatic carcinomas. Transformation of prostatic adenocarcinoma into squamous cell carcinoma after LH-RH agonist intake has been reported in only 8 cases in the literature. To our knowledge, our case is the second pure squamous cell carcinoma observed after hormonotherapy and radiotherapy. We reported a case of a patient with prostatic adenocarcinoma treated by radical prostatectomy followed by radiotherapy. Eleven years later, he had a vesical recurrence of prostatic adenocarcinoma. Our patient had an endoscopic resection followed by injections of Triptorelin. Six months later, he developed a local recurrence of a squamous cell carcinoma.

Evaluation of concordance of Gleason score between prostate biopsy and radical prostatectomy.

BACKGROUND: Histological Gleason score grading is a main determinant of prostate cancer treatment. However, the final histological examination may reveal that concordance rates between biopsy and pathological Gleason sums are inadequate. AIM: To evaluate the concordance of Gleason score between prostate biopsy and radical prostatectomy specimen and to study factors predictive of up-grading of Gleason score at radical prostatectomy. METHODS: We conducted a descriptive and retrospective study including cases of patients who underwent  prostatectomy between 2008 and 2015. We proceeded to a histological examination of 30 cases of radical prostatectomy and 17 corresponding biopsies. The data of the remaining 13 prostate biopsies, not performed in our hospital, have been picked from detailed histological reports. RESULTS: Our results showed that the concordance in the Gleason score was 43% (kappa = 0.11, poor agreement).Gleason score was upgraded in 54% of the cases. At radical prostatectomy, it increased by two  points in one case and by one point in 14 cases. The Gleason score was under-graded on prostatic biopsies in an only 1 case. Using the new classification ISUP 2014, the concordance rate was 26% (kappa = 0.04,  very poor agreement). Gleason score was upgraded in 78% of the cases for Group 1 (SG 3 + 3) and 63% for group 2 (SG 3 + 4). The concordance rate was highest for Group 4 (4 + 3). Variables as age, serum PSA (prostate specific antigen) , numbre of cores, percentage of positive cores, or prostate volume were not significant predictors of upgrading of Gleason score on radical prostatectomy specimen. CONCLUSION: Thus, the high rate of discordance of Gleason score between prostate biopsy and radical prostatectomy specimen implies an understanding of factors predictive of discordance of this score allowing urologists, pathologists and oncologists to support patients in a more suitable way, choosing the appropriate therapeutic modality for each patient.

Paratesticular Angiomyofibroblastoma-Like Tumor: Unusual Case of a Solidocystic Form.

The angiomyofibroblastoma-like tumor of the male genital tract is a rare benign tumor. A total of 34 cases have been reported in the literature. We herein report an exceptional case of solidocystic form in its paratesticular location, in a 79-year-old man. Clinical examination objectified a right testicular induration. Macroscopic examination of the orchidectomy objectified a paratesticular solidocystic tumor formation. Microscopically, the solid area was composed of vessels with small caliber and turgidity of endothelial cells. These vessels were surrounded by clusters of epithelioid cells, sometimes having the appearance of giant cells. They were associated with spindle cells. The cystic area was uncoated. Immunohistochemically, the fusiform cells expressed Desmin and Smooth Muscle Actin. Endothelial cells and clusters of cells surrounding large vessels expressed CD34. The expression of receptors for estrogen and progesterone was negative. To our knowledge, this is the second solidocystic case of angiomyofibroblastoma-like tumor of male genital tract.

Reclassification of gastrointestinal mesenchymal tumors.

BACKGROUND: Gastrointestinal stromal tumors - commonly called GISTs - are rare; yet, they represent an important type of mensenchymal tumors arising within the gastrointestinal tract. The acronym GIST was introduced in 1998 to define a well established pathological entity which bears a highly specific marker called KIT (CD117). Scientific interest for these tumors in recent years is mainly due to the progress in identification by immunohistochemistry and the advent of targeted molecular therapy. AIM: To reclassify mesenchymal tumors of the digestive tract using advanced immunophenotyping. METHODS: We examined the digestive tissue tumors operated at the Principal Military Hospital of Instruction of Tunis over a 19-year period from 1992 to 2011. RESULTS: We collected 22 cases of benign mesenchymal tumors of the digestive tract. Tumors were initially diagnosed as leiomyomas (4 cases), schwannomas (2 cases), gastrointestinal stromal tumors (14 cases), a leiomyoblastoma and a mesenchymal tumor with fusiform cells. The immunohistochemical study has allowed to correct some diagnoses and, in one case, the block has been exhausted. In total, we selected 18 cases of gastrointestinal stromal tumor, a tumors. The final diagnosis of GIST was confirmed by the positivity of C-kit or DOG1. CONCLUSIONS: The combined use of C-kit and DOG1 ensures accurate diagnosis of GIST. The DOG1 has allowed us to detect the 3 stromal tumors negative for C-kit. This antibody has achieved a diagnostic gain of 15 %. The rate of GIST tumors labeled increased from 71 % to 86 % among mesenchymal tumors.