Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

BACKGROUND: As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. METHODS: A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10 years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. RESULTS: Five hundred and ninety patients were included, with a median follow-up of 28 months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3 years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. CONCLUSION: Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Impact of review of histopathology specimens at a tertiary oncology hospital in Eastern India-lessons learnt.

A central review of histopathology specimens at tertiary oncology hospitals is important for optimum patient care in the modern era of personalised medicine. The challenges of healthcare delivery and access to ancillary investigations faced by a pathologist from the Indian subcontinent are different from the western world. We undertook an audit to analyse the differences of opinion between the diagnosis offered at peripheral hospitals and a tertiary oncology hospital in Eastern India. By analysing the differences, common pitfalls and diagnostic discrepancies are identified which need to be addressed in future. This audit also highlights the need of setting up of tertiary oncology diagnostic centres to help both peripheral pathologists and cancer care clinicians like a hub and spoke model. This is most needed for haematopathology, soft tissue and gynaecologic oncology where the need of ancillary investigations is high.

Papillary thyroid carcinoma with nodular fasciitis-like stroma: a rare variant.

Papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) or nodular fasciitis-like stroma (PTC-NFS) is a rare morphological variant of PTC with a favorable prognosis. There is a paucity of molecular data regarding this entity. We present the case of a 20-year-old female who presented with a palpable mass over the anterior aspect of the neck for the past 3-4 months, which was diagnosed as PTC-NFS. Ultrasonogram of the neck revealed a bulky left lobe of thyroid that contained a well-defined heterogenous lesion measuring around 24 × 26 × 36 mm with involvement of the adjacent isthmus. She underwent a total thyroidectomy with central compartment lymph node dissection. Histological examination revealed a biphasic tumor with epithelial and stromal components resembling nodular fasciitis. Two dissected lymph nodes showed metastasis of the epithelial component only. On immunohistochemistry, BRAF mutant protein expression was evident in the epithelial component only, while ß-catenin was negative in both the components. The histopathological diagnosis of papillary thyroid carcinoma with nodular fasciitis-like stroma was offered. Sanger sequencing revealed a BRAFV600E (c.1799T>A, Val600Glu) mutation. Post-operatively, no residual tumor was detected on ultrasound and radioiodine scans. The patient was doing well at follow-up of 9 months. PTC-NFS/DTF is a histological variant of PTC with a favorable prognosis. Our index case was associated with the BRAF mutation, which was restricted to the epithelial component. Thorough sampling of the excised specimen is essential in order not to miss the epithelial component, which, in most reported cases (including ours) appears to be small.

Trilogy Revisited: A Case Report of Co-Existing Nevus Sebaceous with Syringocystadenoma Papilliferum and Tubular Apocrine Adenoma.

Nevus sebaceous of Jadassohn is a cutaneous hamartoma that is associated with various benign and malignant cutaneous tumors. Syringocystadenoma papilliferum and tubular apocrine adenoma are rare benign adnexal tumors. Simultaneous occurrence of all three tumors at the same site is extremely rare, which has raised several questions regarding their origin and pose a diagnostic challenge owing to considerable overlap in clinical and histological features. However, limited case reports have hindered our understanding of these tumors and their natural behavior. Herein, we report a case of a hairless scalp plaque in a 43-year-old male which on histological examination showed presence of syringocystadenoma papilliferum and tubular apocrine adenoma in the background of nevus sebaceous. We also made an attempt to review the available literature and understand the origin and look for clues to aid in accurate diagnosis of such tumors.

SMILE-like lesion in the anal canal.

Stratified mucin-producing intraepithelial lesion (SMILE) is an intraepithelial lesion with overlapping features of the high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Currently, it is well described in the cervix. We present a case showing similar SMILE-like lesions in the polypectomy specimen from the anal canal along with invasive adenocarcinoma components. This lesion showed an immuno-profile characteristic of a SMILE lesion described in the cervix, such as p63 negativity, high ki67 index, and nuclear positivity for p16. It might be arising from the Human papillomavirus prone transitional region of the anal canal as described in the cervix. However, we could not assure this association and etiological link due to insufficient material in the formalin-fixed paraffin-embedded block. Notwithstanding, we strongly suggest that the HPV is the main driver for this SMILE-like lesion similar to what is described in the cervix. To our knowledge, this is the first case report of a SMILE lesion in the anal canal. Further studies will be required to elucidate the underlying pathogenetic mechanism of SMILE-like lesions described in the anal canal.

Clinical, morphological and immunohistochemical analysis of 13 cases of phosphaturic mesenchymal tumor - A holistic diagnostic approach.

BACKGROUND: Phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT) is a rare tumor characterized clinically by presence of tumor-induced osteomalacia (TIO), subsequent to elevated fibroblastic growth factor 23 (FGF23) levels. This study aims to analyse the morphological spectrum of PMT along with clinico-pathological correlation and immunophenotype profile of this rare tumor. MATERIALS AND METHODS: Detailed histological analysis of all tumors presenting with TIO over past 7 years was done retrospectively. Immunohistochemistry was performed in all cases for SATB2, STAT6, CD34, FGF23, ERG, S100 and smooth muscle actin (SMA). RESULTS: A total of 13 cases were analysed (8 female and 5 male) with mean age of 39.8 years. Five cases were arising from bone while 4 each from soft tissue and nasal cavity/paranasal sinus. All presented with hypophosphatemia, hyperphosphaturia, elevated serum FGF23 and features suggestive of osteomalacia. Histological examination revealed basophilic 'grungy' calcification seen in 7 (53.8%), osteoid formation in 8 (61.5%), chondroid matrix in 4 (30.8%), adipose tissue in 6 (46.2%), osteoclast-like giant cells in 9 (69.2%) and hemangiopericytomatous (HPC like) blood vessels in 7 cases (53.8%). HPC like vessels and adipose tissue were more common in nasal tumors while calcification was more common in tumors arising from bone. All cases showed immunoreactivity for SATB2 and clinical improvement following resection except one case with residual tumor. CONCLUSION: PMT shows varied histological pattern with various matrix components depending on the site of the tumor. Serum FGF-23 is a useful adjunctive marker for diagnosis.

Pathologist's perspectives on reporting of tumour budding in colorectal cancer.

PURPOSE: Tumour budding (TB) is an important adverse prognostic factor in colon cancer, which can also guide adjuvant treatment in stage II colorectal carcinoma. The International Tumor Budding Consensus Conference (ITBCC) recommended a three-tiered scoring system to streamline the scoring of budding across the globe. The goal of this survey is to understand the variation in reporting practice, globally. METHODS: A short survey was designed as an online questionnaire and shared via social media platforms and emails to pathology society groups in various countries. RESULTS: A majority of the 294 respondents (186/294; 63.3%) report budding in colorectal carcinoma. This figure differed significantly from 53.4% in Asia to 97.4% in North America. The most common (56.4%) reason for not reporting TB was because it is yet not a mandatory recommendation in the various datasets (e.g. The College of American Pathologists). The majority (78.9%) of the people who were reporting TB, used the ITBCC scoring system (scoring on a single hotspot 20× field). Most used 10× objective for screening (88.7%) and scored only at the invasive front (88.7%). Immunohistochemistry (8.6%) or deeper cuts (24.2%) were rarely used. TB scoring took 10 minutes or less in most (87.1%). CONCLUSION: Though budding is well accepted among specialist gastrointestinal pathologists, it is still not universally accepted as an important prognostic parameter across the globe. The hesitancy for reporting is due to a combination of lack of clinical demand and extra effort and time involved in counting the ITBCC score.

SMILE-like lesion in the anal canal

Stratified mucin-producing intraepithelial lesion (SMILE) is an intraepithelial lesion with overlapping features of the high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Currently, it is well described in the cervix. We present a case showing similar SMILE-like lesions in the polypectomy specimen from the anal canal along with invasive adenocarcinoma components. This lesion showed an immuno-profile characteristic of a SMILE lesion described in the cervix, such as p63 negativity, high ki67 index, and nuclear positivity for p16. It might be arising from the Human papillomavirus prone transitional region of the anal canal as described in the cervix. However, we could not assure this association and etiological link due to insufficient material in the formalin-fixed paraffin-embedded block. Notwithstanding, we strongly suggest that the HPV is the main driver for this SMILE-like lesion similar to what is described in the cervix. To our knowledge, this is the first case report of a SMILE lesion in the anal canal. Further studies will be required to elucidate the underlying pathogenetic mechanism of SMILE-like lesions described in the anal canal.

Papillary thyroid carcinoma with nodular fasciitis-like stroma: a rare variant

Papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) or nodular fasciitis-like stroma (PTC-NFS) is a rare morphological variant of PTC with a favorable prognosis. There is a paucity of molecular data regarding this entity. We present the case of a 20-year-old female who presented with a palpable mass over the anterior aspect of the neck for the past 3-4 months, which was diagnosed as PTC-NFS. Ultrasonogram of the neck revealed a bulky left lobe of thyroid that contained a well-defined heterogenous lesion measuring around 24 × 26 × 36 mm with involvement of the adjacent isthmus. She underwent a total thyroidectomy with central compartment lymph node dissection. Histological examination revealed a biphasic tumor with epithelial and stromal components resembling nodular fasciitis. Two dissected lymph nodes showed metastasis of the epithelial component only. On immunohistochemistry, BRAF mutant protein expression was evident in the epithelial component only, while β-catenin was negative in both the components. The histopathological diagnosis of papillary thyroid carcinoma with nodular fasciitis-like stroma was offered. Sanger sequencing revealed a BRAFV600E (c.1799T>A, Val600Glu) mutation. Post-operatively, no residual tumor was detected on ultrasound and radioiodine scans. The patient was doing well at follow-up of 9 months. PTC-NFS/DTF is a histological variant of PTC with a favorable prognosis. Our index case was associated with the BRAF mutation, which was restricted to the epithelial component. Thorough sampling of the excised specimen is essential in order not to miss the epithelial component, which, in most reported cases (including ours) appears to be small.

Cytodiagnosis of distant metastases from follicular thyroid carcinoma.

INTRODUCTION: Follicular carcinoma of the thyroid is second most common primary malignancy of the thyroid gland after papillary carcinoma and metastasis is uncommonly seen in these patients. AIMS AND OBJECTIVES: To describe the cytomorphologic features for the accurate diagnosis of distant metastases from follicular carcinoma of thyroid. MATERIALS AND METHODS: A total of 10 aspirates reported as metastatic follicular carcinoma of thyroid were reviewed for the available clinical and radiological details. RESULTS: All the patients were females. Six of these patients presented with subcutaneous and soft tissue swellings, one presented with a lung mass, one with right breast swelling, one with lumbar vertebral lesion and one with left iliac bone involvement. The cytology smears revealed tumour cells predominantly arranged in a repetitive microfollicular pattern with some scattered individually and in sheets. The tumour cells were small, had mild nuclear pleomorphism, round nuclei, low nuclear-cytoplasmic ratio, fine chromatin, inconspicuous nucleoli, and scanty to moderate amount of cytoplasm with some showing marginal vacuoles with "fire-flare" appearance. Occasional microfollicles showed scanty eosinophilic colloid in the center. CONCLUSIONS: Identification and establishment of a correct clinical diagnosis of a distant metastasis from a follicular thyroid carcinoma is a challenging task. We believe that with prior knowledge of characteristic cytologic features, such metastases can be rapidly and accurately diagnosed by fine needle aspiration cytology.