Cribriform-morular variant of papillary thyroid carcinoma with poorly differentiated features: report of a case and review of the literature

Introduction Cribrifrom-morular variant of papillary thyroid carcinoma (CMVPTC) is an uncommon thyroid neoplasm that occurs predominantly in women and is sometime associated with familial adenomatous polyposis (FAP). Some of these tumors may undergo dedifferentiation to poorly differentiated thyroid carcinoma (PDTC). We describe a rare case of this carcinoma in a women without a history of FAP. Case presentation A 49-year-old woman with a history of breast carcinoma presented with a thyroid mass. A CMVPTC was diagnosed after excision. There was no history of FAP. Histological examination showed classical features of CMVPTC in most areas, but about 20% of the carcinoma showed features of a poorly differentiated carcinoma with a solid pattern of growth, increase mitotic activity and a high Ki-67 proliferative index (25%). Immunohistochemical stains were positive for nuclear and cytoplasmic beta catenin staining. These special studies supported the diagnosis. Conclusion CMVPTC with dedifferentiation to PDTC is a rare carcinoma with only 4 previous documented cases in the literature. This aggressive variant of thyroid carcinoma is more common in females, as is CMVPTC, and is often associated with an aggressive biological course. The cases usually express nuclear beta catenin and estrogen, progesterone and androgen receptors have been reported in some cases. Some cases may have somatic alterations of the APC gene and TERT promoter mutations. These carcinomas may metastasize to lung, bones and lymph nodes. Because of its aggressive behavior, patient with this diagnosis should be treated aggressively to control disease spread and mortality from the carcinoma.

Erosive acute colitis associated with intestinal spirochetosis

Background Although usually believed to be harmless, intestinal spirochetosis may active erosive colitis associated with intestinal spirochetosis that may mimic idiopathic chronic inflammatory bowel disease. Case presentation. A 49-year-old homosexual male patient sought medical assistance due to asthenia, rectal bleeding, tenesmus, and diarrhea for one month. He had been using corticosteroids for nine months to treat sciatic nerve pain. Colonoscopy showed rectum and distal sigmoid with diffuse erythema with many surface erosions. Rectal biopsy showed inflammatory changes including chronic changes such as architectural distortion and basal plasmacytosis, and active inflammation including crypt microabscesses. In all large bowel sample, dense colonization of intestinal spirochetosis was observed. Patient also had a positive PCR testing for Chlamydia trachomatis. The patient was treated with metronidazole for 14 days, ciprofloxacin for 14 days and azithromycin (single dose). Symptoms improved and the patient is asymptomatic after two months of follow-up. Conclusion In some high-risk groups, intestinal spirochetosis may cause colonic manifestations with overlapping features with intestinal bowel diseases. Awareness of this association is importance since proper antibiotic therapy against Brachyspira (metronidazole) is highly effective. Coinfection with other sexually transmitted infections is common and proper treatment is required.

Malignant giant solitary fibrous tumour of the mediastinum; masquerading Triton tumour

Background Malignant Solitary fibrous tumour (SFT) is an uncommon mesenchymal tumour with aggressive clinical behaviour as compared to its benign counterpart. There are only a handful of reports of extra-pleural malignant SFT arising from the mediastinum. Case presentation A 68-year-old male, presented with a history of cough and breathlessness for 2 weeks. Computed tomography (CT) scan revealed a large 11.6 × 11.3x18cm anterior mediastinal mass with extension to right hemithorax. The patient underwent excision of the mass after a biopsy confirmation of mesenchymal tumour. Histological examination of resection specimen revealed a spindle cell tumour with hypo and hypercellular areas, arranged in fascicular, focal storiform and hemangio-pericytomatous vasculature pattern. Moderate to marked nuclear atypia, frequent mitosis and areas of necrosis were noted. On immunohistochemistry (IHC), the tumour cells were positive for CD34, Bcl2, MIC2 (dot-like) and focally for S100 and Desmin. Although, the possibility of a malignant peripheral nerve sheath tumour with heterologous rhadomyosarcomatous differentiation (Triton tumour) was considered, however IHC for STAT6 confirmed it to be a malignant SFT. The patient developed recurrence within 1 year after surgery and despite multi-modality treatment (Re-excision, Chemotherapy and Radiotherapy) succumbed within 14 months from point of presentation. Conclusion Malignant SFT is a rare aggressive tumour that should be considered as a differential diagnosis in the mediastinum and a broad panel of IHC markers including STAT6 may be required to confirm the diagnosis.

A call to action: molecular pathology in Brazil

Background Adoption of molecular pathology in Brazil is currently very limited. Of note, there are no programs for training new molecular pathologists in the country; thus, documents compiling nationally applicable information on molecular pathology are few. Methods A selected panel of Brazilian experts in fields related to molecular pathology were provided with a series of relevant questions to address prior to the multi-day conference. Within this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion until a consensus was achieved. Results The panel proposes specific and realistic recommendations for implementing molecular pathology in cancer care in Brazil. In creating these recommendations, the authors strived to address all barriers to the widespread use and impediments to access mentioned previously within this manuscript. Conclusion This manuscript provides a review of molecular pathology principles as well as the current state of molecular pathology in Brazil. Additionally, the panel proposes practical and actionable recommendations for the implementation of molecular pathology throughout the country in order to increase awareness of the importance molecular pathology in Brazil.

TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers

Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups.

Recurrent lymphangioleiomyomatosis in a lung allograft with COVID-19: autopsy case report and literature review

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease of the lung with a characteristic feature of diffuse cystic changes in bilateral lungs. Lung transplantation is considered to be one of the effective treatments in end stage disease. Patients with LAM who underwent lung transplant tend to have more favorable outcome compared to other end stage lung diseases. We report a case of a female patient who was diagnosed with LAM and received bilateral lung transplantation at 45 years of age. Subsequent allograft biopsies were significant for mild acute cellular rejection (Grade A2), for which the immunosuppressive regimen was adjusted accordingly. At 7 years post-transplant, she presented with shortness of breath, cough, and fatigue, and diagnosed with a viral infection. Her chest imaging was unremarkable. However, a transbronchial biopsy was performed to rule out rejection and revealed foci of spindle cells proliferation, with positive HMB-45 and smooth muscle actin immunohistochemical studies, confirming the diagnosis of recurrent LAM. After she was discharged, she was re-admitted 1 week later with severe COVID-19. Her clinical course was complicated by acute respiratory distress syndrome, respiratory failure, and gastrointestinal hemorrhage. The patient passed away on day 36 of hospital stay. Autopsy was requested and confirmed the pathology of recurrent LAM and diffuse alveolar damage from COVID-19.

Assessing viability of a minimally invasive autopsy technique in ascertaining the probable cause of death in patients who were SARS CoV19 positive at the time of their demise

Background SARS CoV-19 was declared as a pandemic by the World Health Organization (WHO), raising up challenges on various levels ranging from therapeutics to diagnostics. The conventional autopsy technique may pose a health hazard to health care workers. A minimally invasive autopsy technique can diminish this hazard. Materials and methods Between August and November 2020, 51 patients who were suffering from Covid-19 at the time of their demise were included. A novel minimally invasive ultrasound-guided technique for procuring tissue samples of major organs was employed which were thereafter subject to histopathological examination. A detailed review of the course in hospital was noted. An analysis was performed to correlate the cause of death ascertained from our minimally invasive technique with the cause of death ascertained clinically. Results There was adequate tissue sampling in 45 cases, where the minimally invasive autopsy technique confirmed the cause of death in all 45 cases (100%) and made it more specific in 5 cases (11.11%). Conclusion Minimally Invasive Autopsy is an easily reproducible technique which has the potential to strengthen the probable the cause of death with reasonable certainty while ensuring safety and ethics.

Applicability of PD-L1 tests to tailor triple-negative breast cancer treatment in Brazil

Background Triple-negative breast cancer (TNBC) is a heterogeneous disease that represents 10–20% of breast cancer cases. The prognosis for advanced TNBC is usually poor, with a median overall survival of approximately 18 months or less. Main text New targeted therapies such as anti-PD-L1 agents are emerging as an option to treat advanced TNBC. A panel of 6 national experts with an active interest in breast cancer convened online. Panel members had either clinical or pathology experience in breast cancer. The experts pre-defined critical questions in the management of PD-L1 in TNBC, and a literature review was performed for selected topics before the online meeting. Conclusion The experts led active discussions involving a multidisciplinary team comprising pathologists and clinical oncologists. The meeting served to discuss the most relevant issues. A total of 10 critical questions for PD-L1+ TNBC were debated and are presented in this review. This article discusses the current landscape for PD-L1 tests in TNBC in Brazil.

Assessment of lymphovascular invasion in early stage endometrial carcinoma -a retrospective study

Introduction Endometrial carcinoma is associated with several known prognostic factors. Recently, lymphovascular invasion (LVI) has gained a prominent position in the risk assessment of early endometrioid endometrial carcinoma, in identifying patients who can benefit from adjuvant radiation therapy. This study aims to assess LVI in early-stage endometrioid endometrial carcinoma accurately with emphasis on its extent /grading. We also propose a few local recommendations for improving LVI reproducibility in endometrial carcinoma to guide future studies. Methods The duration of this retrospective study was 2 years. Early-stage I (Ia and Ib), and grade 1 and 2 endometrioid endometrial carcinomas were included. 03 reviewers independently recorded their findings on H&E stained slides. LVI was graded as none, focal and substantial. In discordant cases, immunohistochemical stain CD 31 was used. All the data was entered in the statistical software SPSS version 26 and analyzed for frequencies. The relationships between various histological parameters assessed and the degree of reproducibility for LVI amongst various observers were also determined. Results Out of a total of 70 cases of endometrioid carcinoma diagnosed on hysterectomy specimen, only 32 met our inclusion criteria. The rate of LVI positivity was 6.3 %, 34.4 %, and 37.5 % respectively for reviewers 1, 2, and 3. The degree of reproducibility in LVI assessment and LVI grading was significant amongst reviewers 2 and 3. Also, a significant association was drawn between tumor grade and LVI. Conclusion Despite limitations in our study we recommend including both LVI assessment and grading in routine reporting formats locally. By adding a second reviewer in LVI assessment and using CD31 in discrepant cases LVI positivity can be significantly increased.