Comparative expression profile of CD10 and cyclin D1 in cutaneous histiocytofibroma and dermatofibrosarcoma.

Dermatofibrosarcoma protuberans (DFSP) and histiocytofibroma (HF) are two rare fibrohistiocytic tumors, with some overlapping pathologic features. Immunohistochemistry is very useful in these cases. CD34 is a commonly used marker. However, the increasing cases of CD34 negative DFSP make it pressing to test other immunohistochemical markers that could help in the differential diagnosis. DFSP is known to harbor COL1A1-PDGFB rearrangement. Tumors in the differential diagnosis of DFSP usually lack this molecular signature. Recent studies suggested the interaction of PDGFB and PDGF receptor b with various signaling pathways, including the Akt-mTOR pathway. Cyclin D1, one of the oncoproteins activated in this pathway, may represent a promising useful biomarker in the differential diagnosis. On the other hand, CD10 expression in specialized mesenchymal skin cells, and especially in fibrohistiocytic skin tumors has been reported, which raises the interest of using this biomarker in HF and DFSP. In this study, we aimed to compare the expression of CD10 and cyclin D1 in 15 cases of DFSP and 15 cases of HF and discuss their potential contribution in the differential diagnosis.

Tumor budding is a prognostic factor linked to epithelial mesenchymal transition in pancreatic ductal adenocarcinoma. Study report and literature review.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastatingly poor prognosis. Surgical resection is undertaken in only 20% of patients. Most of well-known prognostic factors reflect tumor stage more than its biology. So it is important to identify new biological indicators related to survival in order to develop new therapies. OBJECTIVE: To determine the relation between tumor budding and Epithelial Mesenchymal Transition (EMT) and to evaluate their impact on survival for patients after resection of PDAC. METHODS: We herein report a retrospective study of 50 patients with resected PDAC. Tumor budding, immunohistochemical expression of vimentin and other standard factors were correlated with survival using the Kaplan-Meier method and Cox multivariable survival analysis. For tumor budding assessment, an inter-observer variability study was performed using 100 images of tumor slides stained with Hematoxylin & Eosin and Pan-Cytokeratin. RESULTS: Tumor budding was present in all tumors. A substantial agreement between six pathologists was established in distinguishing high-grade from low-grade budding (κ = 0.6 and 0.73 for H&E and PCK images respectively). High-grade budding was identified in 56% of tumors (28/50). It was an adverse prognostic factor independent of tumor size, resection margins status, nodal status and vascular invasion (p = 0.008). Tumor budding was significantly associated with vimentin expression (p = 0.002). CONCLUSIONS: The association of tumor budding with vimentin expression supported the idea that EMT is a key process in PDAC responsible for progression and drug resistance. Consequently, the elucidation of EMT molecular biology and development of new targeted therapy may improve disease outcome.

Papillary thyroid tumors: Diagnostic value of CD56 and Cytokeratin 19.

INTRODUCTION: Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features (NIFTP) is a tumor composed exclusively of follicles lined by cells having nuclear characteristics of papillary carcinoma. Morphological diagnosis is often difficult especially in the cases in which these nuclear abnormalities are focal. AIM: To investigate the contribution of the immunohistochemical study with anti CD56 and anti cytokeratin 19 in the positive diagnosis of NIFTP. METHODS: This is a diagnostive, retrospective study of 40 thyroid specimens including 15 NIFTP, 10 classical form papillary carcinoma (CPC) and 15 vesicular adenomas (AV), collected over a period of eighteen months (December 2013-May 2015). RESULTS: Negativity with anti-CD56 was noted in 16 cases: 9 cases of NIFTP and 7 cases of CPC. A diffuse staining was noted in 14 cases of AV. Positivity with anti-Cytokeratin19 was noted in 38 cases: 14 NIFTP, 10 CPC and 14 AV. For the diagnosis of NIFTP, the sensitivity of CD56 was 60% and specificity of 100%. The sensitivity of the Cytokeratin 19 was 93,3 % and specificity of 33,3%. CONCLUSIONS: Considering the good sensitivity and specificity of the CD56, it is possible to apply immunohistochemistry for definitive diagnosis of NIFTP and to differentiate it from adenoma. The cytokeratin 19 does not have a big contribution to distinguish between benign and malignant lesions.

Intracranial grade I meningiomas: Confrontation between histological examination and magnetic resonance imaging.

INTRODUCTION: Meningiomas are tumors derived from arachnoid cells. More than 90% of cases have a benign clinical course and are classified as grade I according to the World Health Organization. A confrontation between radiologic findings and pathological examination is necessary to predict the grading of meningiomas. OBJECTIVES: To study the radiological presentation by magnetic resonance imaging (MRI) and pathological features of intracranial meningiomas grade I. METHODS: This was a retrospective descriptive study of a series of 35 cases of grade I meningiomas. A review of MRI images was performed in this study. RESULTS: Our series consisted of 25 female and 10 male patients with a mean age of 49.2 years.The tumor was localized at the base of the skull in 20 cases (57.14%). The average size was 49 mm. At MRI, all meningiomas were solid showing enhancement after injection of contrast agent. This enhancement was homogeneous in 21 cases and heterogeneous in 14 cases. The edema was broad and extended in 15 cases, reduced in 8 cases and absent in 12 cases. The mean minimum apparent diffusion coefficient was 0.77 and the mean maximum average diffusion coefficient was 0,8. On histological examination, the meningioma was of meningotheliomatous type in 23 cases (65.7%), fibroblastic in 8 cases (22.9%), transitional 3 cases (8.6%) and angiomatous in one case (2,8%). CONCLUSION: Although the final diagnosis of meningioma is mainly based on pathological examination, comparison with imaging is also important to orient the pathologist.

Neuroendocrine differentiation in basal cell carcinoma.

Basal cell carcinoma (BCC) is the prototypical basaloid tumor of the skin. It may show various patterns simulating other cutaneous tumors due to its pleomorphism. It may have an unusal pattern of differentiation such as squamous, sebaceous, apocrine, eccrine, pilar, and endocrine differentiation. In order to establish the relative frequency of neuroendocrine differentiation in BCC, we performed a retrospective study of 33 consecutive BCCs using conventional immunohistochemistry with two neuroendocrine antibodies: Chromogranine A and synaptophysine. The age of the patients ranged from 17-83 years with mean of 65 years. The male to female ratio was 16:17. In immunohistochimestry, Chromogranine A was seen in 72.2% (24/33) while Synaptophysine was positive in 9.09% (3/33). Their expression was cytoplasmic and membranous and was seen in the periphery of these tumors in the overlying cells. Positive staining of chromogranine A was high (75-100% of tumors cells) in 9%, intermediate (25-75% of tumors cells) in 33% of cases and relatively low (<25%) in 30.3% of cases.

Gastrointestinal neuro-endocrine tumors: retrospective study of 36 cases.

BACKGROUND: Neuroendocrine tumors (NETs) of the gastrointestinal tract are a heterogeneous group of tumors which have different malignant potential and evolution. The World Health Organization (WHO) has set up a new classification of gastrointestinal NETs in 2010. However, it does not evaluate the risk of malignancy for each tumor. AIM: To evaluate the prognostic impact of the WHO classification in 2010 by reclassifying the tumor according to new recommendations and to identify histoprognostic factors to better predict changes. METHODS: This is a descriptive retrospective study of 36 cases of gastrointestinal NETs, collected at the pathological anatomy department in Rabta hospital, over a period of 11 years from 2003 to 2013. RESULTS: Our series included 11 NETs of Appendix, nine of the pancreas, seven of the small bowel, four of the stomach, three of the rectum, one of the colon and one of the esophagus. The mean age of patients across all sites, was 50.3 years old and the sex ratio was 0,44. The tumors were classified according to the 2010 WHO classification. They were divided into: G1 in 27 cases (75%); G2 in three cases (8.3%); G3 small cell carcinoma in two cases (5.6%); G3 large cell carcinoma in one case (2.8%) and mixed adeno-neuroendocrine carcinoma in three cases (8.3%). CONCLUSION: Our study has shown limits of the latest 2010 WHO classification of NETs. The prognosis of these tumors could be better predicted by the evaluation of other histoprognostic factors and by the improvement of criteria defining histological degrees including tumor size.

Prognostic value of Ki67: comparison of the proliferation index between meningiomas with and without infiltration of glial tissue.

BACKGROUND: Although generally considered benign, meningiomas can cause significant morbidity and mortality.  Histologic grade is the most useful morphologic predictor of recurrence. OBJECTIVES: To compare Ki67 labeling index between meningioma grade I and meningioma grade II with brain invasion. METHODS: We analyzed 20 primary meningioma, 10 of which were grade I and 10 of which were grade II. Ki67 proliferative indices were determined in all cases. RESULTS: The patient population consisted of 9 males and 11 females with mean age of 60 years. For meningioma grade I, the Ki67 labeling index varied between 1 and 15% with an average of 3.1%. A diagnosis of gradeII meningiomas was made solely on the basis of brain invasion. The immunohistochemical study noted that the Ki67 index varied between 1 and 20% with an average of 6,8%. CONCLUSION: The Ki67 labeling index shows a significant increase from grade I to grade II.  It may provide useful prognostic information.

Malignant transformation of nasal inverted papilloma into sarcomatoid carcinoma.

A 57 year-old, male presented with a chronic unilateral nasal obstruction and epistaxis. Intranasal endoscopy showed multiple polypoid lesions. The computed tomography exam revealed a heterogeneous mass that occupied the right nasal cavity with osteolysis of the middle and lower cone causing fluid retention of the right maxillary sinus. He underwent resection of these lesions. Pathological examination revealed malignant transformation of nasal inverted papilloma into sarcomatoid carcinoma. This case report highlights the importance of considering malignant transformation in the differential diagnosis of polypoid lesions.

A Challenging Cutaneous T-Cell Lymphoma.

Cutaneous peripheral T-cell lymphomas not otherwise specified (CPTL-NOS) are rare neoplasms accounting for just 2% of cutaneous peripheral T-cell lymphomas (CPTL). Only very few case series have been reported. They represent a phenotypically and prognostically heterogenous group of CPTL that do not fit into any of CPTL well-defined subtypes. The authors report a case of a 64-year-old man with simultaneous plaque-like lesions and disseminated nodules growing rapidly on the face, trunk, and extremities over a 6-month period. There was no a history of preceding patches, erythematous plaques, rash, or pruritic lesions. These lesions were extending over 80% of the skin surface. Histopathologic analysis revealed dense diffuse infiltrates composed of mostly medium-sized to large lymphoid cells throughout the entire dermis without epidermotropism. Neoplastic cells were atypical with markedly pleomorphic nuclei. Immunohistochemistry showed that the tumor cells were positive for CD3, CD4, and CD5 with a loss of CD7. They were negative for CD20, CD8, CD56, CXCL13, PD1, TIA-1, granzyme-B, perforin, CD25, and CD30. The proliferative fraction was low, with MIB-1 labeling less than 10% of cells. The authors diagnosed the patient with primary CPTL-NOS. Despite the rarity of these tumors, clinicians as well as dermatopathologists and pathologists should be familiar with these rare CPTL especially because most of these lymphomas have an aggressive behavior and exhibit an unfavorable prognosis.

Lipomembranous Panniculitis Associated With Venous Insufficiency, Morphea, and Psoriasis.

A 45-year-old obese woman diagnosed with morphea on her leg, presented with a 7-year history of cutaneous depressions on her thigh, chest, and back. She recalled that the lesions followed a three-phase course: edema, hardening, and atrophy. Clinical examination revealed a cutaneous indurated depression localized to the thigh, chest, and the back (Figure 1).

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.

Overlap syndrome of seronegative primary biliary cholangitis and small duct primary sclerosing cholangitis: a first case report and literature review.

Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) are distinct liver diseases. Cases combining PBC and PSC, are extremely rare. Here, we present a case of a 39-year-old woman with a history of colonic Crohn's disease treated with azathioprine. Discontinuation of the medication was prompted by abnormal liver function tests, but subsequent evaluations revealed persistent liver injury. Extensive diagnostic investigations, including imaging, serological tests, and liver biopsy, were conducted leading to a diagnosis of PBC-PSC overlap syndrome based on the presence of concentric lamellar fibrosis and chronic non-suppurative destructive cholangitis. The patient responded well to ursodeoxycholic acid treatment. This case emphasizes the importance of recognizing and diagnosing rare overlap syndromes, particularly those involving PBC and PSC, to ensure appropriate management and improve patient outcomes.

Intracranial inflammatory pseudotumour related to IgG4: A very rare case.

Background: Intracranial inflammatory pseudotumours (IPT) are rare entities that frequently lead to misdiagnosis with malignant lesions. The identification of these lesions is difficult, but important to avoid inadvertent iatrogenicity and to adjust therapeutic protocols. Case Presentation: We report the case of a 30-year-old man who presented a single tonic-clonic seizure. Brain imaging showed a right frontal lesion with intra and extra axial components. Facing the radiologic presentation, a brain tumor was suspected, thus the patient underwent surgery. Pathological exam concluded to a plasma cell granuloma. A whole-body CT-scan showed only a thoracic aortitis. Complete blood work studies came back negative. The patient was also tested for an array of antibodies among which antinuclear antibodies were positive (blood level superior to 1/100). CSF evaluation revealed clear fluid with normal glucose concentration, normal protein levels and lymphocytic pleocytosis. Finally, IgG-4 plasma levels were elevated which led to the diagnosis of an IgG4-RD. The patient was put under prednisolone with a favorable outcome. Conclusion: IPT have several etiologies, among which IgG4 related disease may be one of the less known as only 2 cases have previously been reported. Herein, we report a new case of a young man who presented for seizures related to an intracranial lesion of an IgG4 related disease. The challenge is to suspect such conditions to avoid unnecessary surgeries.

Evolution and prognosis of bladder papillomatosis managed by endoscopic resection and endovesical BCG therapy : about 24 cases.

BACKGROUND: Bladder papillomatosis is a diffuse tumor proliferation even up almost all of the bladder mucosa. We analyzed prognosis of this rare entity after conservative treatment. METHODS: We retrospectively analyzed epidemiological, clinical, therapeutic and evolutive data in 24 patients with newly diagnosed bladder transitional cell carcinoma papillomatosis. All patients underwent a complete endoscopic transurethral resection (TUR) with curative intent. A second look was performed within 30 days. The intravesical therapy regimen consisted on weekly instillations for 6 weeks, and then monthly for 6 months. If the tumor recurred without muscle invasion, TUR was repeated with a second intravesical BCGtherapy regimen. Parameters investigated included age, gender, risk factors, cystoscopic findings (aspect, multiplicity and location of bladder lesion), tumor stage, tumor grade, recurrences and progression times from diagnosis to last follow up. RESULTS: The mean age of the patients at initial diagnosis was 64,9±6,1 years. They were males in 23 cases. Initial cancer staging was as follow: pTa (n=6) and pT1 (n=18). The recurring tumors were reported in 17 patients (70,8%). They were stage Ta in 5 patients and stage T1 in 12. The median interval of time between the initial TUR and the first recurrence was 10,3 months. Six patients remain tumor free. From the 17 recurrences, 6 patients developed progression with muscle invasion in 4 of them. Radical cystectomy with ileal conduit was performed in 3 patients and one patient died before radical treatment. Univariate analysis didn't reveal any prognostic factor: age (p=0,7), tumor location and aspect (p= 0,7 and p= 0,5 respectively), tumor stage (p=0,7) and grade (p=0,09). CONCLUSION: TCC bladder papillomatosis is a rare entity. TUR with intravesical BCG therapy may be indicated as a first option despite correct follow up. Radical cystectomy should be considered in cases of recurrent or non-resectable tumours.

[Cutaneous carcinoma induced by radiotherapy: a report of 31 cases]. / Carcinomes cutanés induits par la radiothérapie: a propos de 31 cas.

BACKGROUND: Depilatory radiotherapy was used in the sixties as a treatment for ringworm in Tunisia. Subsequently some of these patients developed radio-induced carcinomas of the scalp. AIM: To present the epidemiological, clinical, pathological,therapeutic features and out come of radio-induced cutaneous carcinomas. METHODS: We conducted a retrospective study performed in the dermatology department of the La Rabta hospital of Tunis over a 6- year-period recording all histologically confirmed carcinomas in patients irradiated in childhood for tinea capitis. RESULTS: Thirty one patients were included with 49 tumors: 47 basal cell carcinomas and 2 squamous cell carcinomas. The average latent period between the irradiation and the appearance of the carcinomas was of 35.7 years. The average age was 53 years. A male predominance was noted, with a sex ratioM/F of 6.75. Clinically, basal cell carcinomas were nodular in all cases. Surgery was indicated in 90% of cases. Cryosurgery and radiotherapy were used respectively in 1 and 2 patients. CONCLUSION: Our study shows that radio-induced cutaneous carcinomas are widely dominated by basal cell carcinoma. They arise, approximately, ten years earlier than carcinoma in patients with no history of scalp irradiation. However X-ray exposure does not seem to influence clinical or histological presentation, therapeutic modalities nor prognosis of these tumors. The prognosis of radioinduced cutaneous carcinomas was globally similar to that of other cutaneous carcinomas with same histological type and equivalent degree of invasion.