Carcinoma Cuniculatum Arising in the Tongue

Carcinoma cuniculatum (CC) is a rare, distinct clinico-pathological variant of squamous cell carcinoma (SCC) that is defined histologically by the characteristic infiltrative pattern of a deep, broad, and complex proliferation of stratified squamous epithelium with keratin cores and keratin-filled crypts. Herein, we present a case report of CC of the oral tongue and discuss its diagnosis, management, and outcome, as well as briefly review the world literature. To our knowledge, this is the first documented case of CC of the tongue to be reported in the English literature. We draw attention to its clinico-pathological features and highlight that awareness of this entity as a distinct variant of SCC facilitates its correct management.     

Plexiform Schwannoma of the Oral Cavity: Report of Eight Cases and a Review of the Literature

Plexiform schwannoma represents an unusual schwannoma variant, characterized by multinodular growth grossly and/or microscopically. A review of the English-language literature reveals only 28 previously reported cases involving the oral cavity, and herein we present 8 additional cases. Among these 36 patients, the average age at diagnosis was 28 years (range 5 to 62 years), with a female-to-male ratio of 1.4:1. The most frequently involved sites were the tongue (n = 13) and lip (n = 11). Lesion duration prior to presentation averaged 5.3 years (range, 6 weeks to 26 years). The average lesion size was 2.1 cm (range, 0.3 to 16 cm). The typical clinical presentation was a painless mass, although infrequent findings included pain/discomfort, paresthesia, difficulty chewing, and limited buccal mobility. All cases clinically appeared as a solitary mass or localized cluster of tumor nodules, with the exception of one patient who had neurofibromatosis 2 (NF2) and exhibited two distinct nodules on the tongue and buccal mucosa. In addition, extraoral neural neoplasms were evident in four patients, including three with NF2. Typical microscopic findings included multiple well-circumscribed tumor nodules, each surrounded by a perineurium-derived capsule with immunoreactivity for epithelial membrane antigen. The nodules contained characteristically bland and diffusely S-100-positive spindle cells arranged in Antoni A and B patterns; however, modest nuclear pleomorphism was evident in three cases. Most patients (n = 23) were treated by excision or enucleation and curettage, and three patients experienced recurrence. Unlike plexiform neurofibromas, plexiform schwannomas exhibit only a weak association with neurofibromatosis and have no known malignant potential.     

Clinicopathologic Characteristics of Young Patients with Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) occasionally occurs in young patients and is likely to be distinct from OSCC in older patients. In this retrospective study, we described the clinicopathologic features and outcome of 150 OSCCs that were diagnosed in patients 40-year-old or younger. Most patients (63%) were non-smokers. The most common site of the primary tumor was oral tongue (n = 131, 87%), followed by gingiva (n = 9), buccal mucosa (n = 8) and lip (n = 2). The median patients'' age at presentation was 34 (range: 16–40). Seven patients (5%) had Fanconi anemia with the gingiva being the most common location (4/7, 57%). All OSCCs were of keratinizing type. All cases tested for high-risk HPV (n = 34) were negative. On univariate analysis, high tumor budding was associated with decreased overall survival (OS) and distant metastasis free survival (DMFS), pattern of invasion correlated with OS and tumors with high stromal tumor infiltrating lymphocytes (sTIL) were associated with improved locoregional recurrence free survival (LRFS). Compared with patients 31 to 40-year-old, OSCC in the younger group was associated with significant less alcohol consumption (p = 0.011) and decreased DSS (p = 0.003) and DMFS (p = 0.023). On multivariate analysis, younger age (30 years or younger) was an independent prognostic factor for worse OS and DSS, whereas histologic grade was an independent prognostic factor for DSS. In summary, most OSCC in young patients occurred in non-smokers and did not occur in association with Fanconi anemia. Independent prognostic factors included age at presentation (30 years or younger) for OS and DSS, and histologic grade for DSS.     

Distinguishing Parathyromatosis,Atypical Parathyroid Adenomas,and Parathyroid Carcinomas Utilizing Histologic and Clinical Features

Parathyromatosis is displaced parathyroid tissue in the neck and mediastinum related to prior surgery. Parathyromatosis can be difficult to distinguish from atypical adenoma and parathyroid carcinoma. The aim of this study is to evaluate clinical and morphologic features that may differentiate parathyromatosis, atypical adenoma, and parathyroid carcinoma. Cases of parathyromatosis, atypical adenoma, and parathyroid carcinoma were identified. Index cases were reviewed by consensus for histologic features, including stromal, cytologic/architectural, and invasive features. Ki67 was performed on index cases and scored using the Adsay method. Clinical information was gathered from the electronic medical record. 4 parathyromatosis, 17 atypical adenoma, and 6 parathyroid carcinoma were included. Parathyroid carcinomas were more likely to display coarse chromatin with nucleoli (P = 0.04), infiltrative invasion (P < 0.01), and metastasis (P < 0.01). Only parathyromatosis showed circumscribed invasion. Infiltrative invasion was more common in cases with progression (P = 0.046) and metastasis (P < 0.001). Necrosis and perineural invasion were only present in cases with progression and were more frequent in cases with metastasis (P = 0.079 and P = 0.19, respectively). There were no differences in presence of a fibrous capsule, capsular invasion, intralesional fibrous bands, random endocrine atypia, solid growth, Ki67 index, gland size/weight, serum PTH/calcium levels, and locoregional recurrence rates. There is overlap in the histologic features in parathyromatosis, atypical adenoma, and parathyroid carcinoma. While perineural, vascular, and infiltrative soft tissue invasion should remain diagnostic of malignancy, other atypical features such as solid growth, coarse chromatin with nucleoli, and necrosis should raise concern for recurrence and/or metastasis, and can be present in parathyroid lesions with and without recurrence.     

Carcinoma Cuniculatum of the Esophagus and Tongue: Report of Two Cases,Including TP53 Mutational Analysis

Carcinoma cuniculatum (CC) is a rare variant of extremely well differentiated squamous cell carcinoma. We present the clinicopathological features of two cases of CC; one lingual and one esophageal case with a molecular genetic study regarding the TP53 gene mutational status. Case 1 was a 62 year old male with enlarging chronic ulcer in the tongue. Case 2 was a 77 year old male with progressive dysphagia and odynophagia. Both patients were treated surgically. Both tumors showed deeply invaginating, keratin-filled, burrowing crypts lined by very well differentiated squamous epithelium. The esophageal tumor showed varying degrees of reactive nuclear atypia largely limited to the areas with dense intratumoral infiltration of neutrophils. No mutation of TP53 was identified in the esophageal case. Cytologic atypia limited to areas of significant acute inflammation may occur in CC and should, in the absence of aggressive stromal invasion, not preclude a diagnosis of CC.     

Parathyroid Carcinoma: A Single-Institution Experience with an Emphasis on Histopathological Features

Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004–2018. The study cohort comprised twenty cases of PC. The median age was 49 years (range 21–73 years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4 cm (range 0.8–3.5 cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months). Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.     

Orbit Solitary Fibrous Tumor: A Proposed Risk Prediction Model Based on a Case Series and Comprehensive Literature Review

Solitary fibrous tumors (SFTs) of the orbit are rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, 12 cases of orbital SFTs were analyzed in conjunction with a review of 263 cases reported from the English literature in order to develop a risk prediction model. SFTs of the orbit were equally distributed between males (n = 5) and females (n = 7) with a mean patient age of 46.8 years (median 44.5 years; range 18–76 years) at initial diagnosis. The patients typically presented with swelling or mass around the orbit, with proptosis (n = 10), ptosis (n = 5), and visual changes (n = 6). Tumors were orbital (n = 10) or upper eyelid (n = 2). Mean tumor size was 2.5 cm (median 2.6 cm). Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. By immunohistochemistry, all cases had a strong nuclear STAT6 expression. All patients were initially managed with excision or biopsy, three with presurgical embolization. The two patients with biopsy only had persistent disease (mean 37.2 months), but a third patient developed distant bone metastasis at 86.9 months. Overall mean follow-up was 73.1 months: 9 patients are alive or dead without disease (mean 77.9 months), two patients with persistent disease, and one patient with metastatic disease at last follow-up (102 months). Incorporating cases sufficiently reported in the literature, a risk prediction model based on age > 45 years, tumor size > 3 cm, tumor necrosis, mitoses of > 4/2 mm², moderate to high cellularity, and moderate to severe pleomorphism allows for risk stratification for the development of local recurrence and distant metastasis. In conclusion, orbital SFTs are rare, but can be reliably diagnosed based on the presence of characteristic morphologic features and STAT6 immunohistochemistry. Orbital tumors tend to show a higher frequency of local recurrence than distant metastasis, which can be predicted by a risk stratification model unique to orbital tumors. With late disease common, long term clinical follow-up is recommended.     

Neuroendocrine Neoplasms of the Larynx: A Clinicopathologic Analysis of 27 Neuroendocrine Tumors and Neuroendocrine Carcinomas

Laryngeal neuroendocrine neoplasms (NENs) are rare and heterogeneous, encompassing well-differentiated neuroendocrine tumors (NETs; grade 1, 2, and 3), neuroendocrine carcinomas (NECs, small cell and large cell types), and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). We aimed to study the clinicopathologic spectrum of these neoplasms. A retrospective review of all primary laryngeal NENs diagnosed from 2005 to 2017 was undertaken. Mitotic index was divided into < 2, ≥ 2–10, and > 10 mitoses/2 mm², with a Ki-67 labelling index of < 2%, ≥ 2–20%, and > 20% for the NET grade 1, 2 and 3 categories, respectively. A total of 27 patients were included. The median age at presentation was 60 years; the male-to-female ratio was 8:1. Supraglottis (n = 22) was the most frequently affected subsite. There were 9 NETs grade 2 (G2), and 18 NECs cases. There were no NET grade 1 or 3 cases in our cohort. Among the NETs G2, the morphology was epithelioid (2), plasmacytoid (3), clear (2), oncocytic (1), and rhabdoid (1). Unique ‘glomeruloid structures’ (n = 5), calcification (n = 3), lymphoid aggregates (n = 5), intranuclear inclusions (n = 2), hyaline globules (n = 3), and Leisegang rings (n = 2) were identified. NECs comprised 16 small cell neuroendocrine carcinoma and 2 large cell neuroendocrine carcinoma. On immunohistochemistry, tumor cells expressed AE1/AE3 (86%), synaptophysin (100%), chromogranin (100%), INSM1 (100%), calcitonin (33.3%). In the NEC group, p53 aberrant expression (87.5%), Retinoblastoma (Rb) loss (88.2%), and diffuse p16 immunoreactivity (66.7%) were additionally observed. Lymph-node metastasis was detected in 62.5% and 85.7%, while distant metastasis in 55.6% and 76.9%, respectively in NET G2 and NEC. Laryngeal NENs are aggressive neoplasms with a high rate of nodal and distant metastasis. Awareness of the wide pathologic spectrum of laryngeal NENs and appropriate use of IHC is needed to render an accurate diagnosis. Ki67 assessment is strongly recommended for laryngeal NEN prognosticationSupplementary InformationThe online version contains supplementary material available at 10.1007/s12105-021-01367-9.     

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

Intra-oral Acantholytic Squamous Cell Carcinoma: 55 Cases. Is this Variant more Aggressive?

We aimed to collect and analyze available cases of intraoral acantholytic squamous cell carcinoma (aSCC), that consisted of the authors’ cases and cases derived from the existing literature, with an emphasis on the pathological staging and patient outcome. Our research question was whether aSCC is more aggressive than conventional SCC. The literature was searched for documented cases of aSCC involving the intra-oral mucosa, excluding those from the lips and tonsils, and seven new cases were added from our files. The authors compared the obtained aSCC data to existing data for conventional SCC. Fisher Exact or Pearson’s χ² tests were used for categorical variables. Fifty-five cases of intraoral aSCC were reviewed, of which 48 were retrieved from the literature. Analysis of the published cases was reinforced by contacting the authors of all the papers with incomplete data for further clarifications. The most common sites of aSCC were the tongue (24/55) and the maxilla/maxillary gingiva and/or palate (11/55). The overall survival rate was 36/53 (67.9%) with a mean follow-up period of 22 months against 62.5% for conventional SCC (p = 0.6). No statistically significant difference between the two variants of the tumor with respect to the oral cavity was detected. The differences in age, sex, survival rate, staging, and locations were not statistically significant. Based on the available data from 55 cases, there is no evidence to suggest that aSCC is more aggressive than conventional SCC in intraoral cases.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12105-021-01368-8.     

Evaluation of Histopathological Risk Model in a Cohort of Oral Squamous Cell Carcinoma Patients Treated with Accompanying Neck Dissection

To investigate the applicability of the validated histological risk model in a cohort of oral cavity squamous cell carcinoma patients treated concurrently with neck dissections. Primary tumours from 85 patients with primary excision of T1 and T2 Oral Squamous Cell Carcinomas (TNM 7th edition) including neck dissection were scored by three pathologists in consensus according to the validated risk model. The risk score data, along with traditional dataset values, were analysed to determine possible association with nodal metastasis and extracapsular spread. Seventy-two patients (54%) were classified with low or intermediate risk and 62 (46%) patients were ‘high risk’. A chi squared test showed that cases with nodal metastasis were highly statistically significant with the overall risk model score (X² = 22.62 p = 0.0001). None of the neck dissections from tumours with low risk score showed evidence of metastasis (NPV = 100%) suggesting the risk score may also be a useful tool for predicting an absence of metastasis. Risk assessment of low-stage oral squamous cell carcinoma primary tumours may be predictive of the presence or absence of metastasis at presentation. Knowledge of the risk score and its constituent parts may inform treatment decisions at multidisciplinary meetings. Low risk squamous cell carcinoma may be a rare variant with low metastatic potential and excellent long-term survival.     

Efficacy of One‐stage Paravertebral Approach using a Micro‐Tubular Technique in Treating Thoracic Dumbbell Tumors

ObjectiveThe aim of the present study was to investigate the feasibility and efficacy of one‐stage surgical resection of thoracic dumbbell tumors using a paravertebral approach and a micro‐tubular technique.MethodsClinical data of thoracic dumbbell tumors resected using a paravertebral approach and a micro‐tubular technique (14 mm, non‐expandable type) in the Department of Neurosurgery at our hospital from July 2014 to July 2019 were retrospectively analyzed. Tumors were found between T1 and T12 vertebrae. Operation time, blood loss, hospitalization, recovery of neurological function, complications, the Japanese Orthopaedic Association (JOA) score, and the visual analogue scale (VAS) score were used to evaluate clinical efficacy.ResultsIn all 31 cases, tumors were completely resected in one operation, with a mean blood loss of 53.23 ± 33.08 mL (20–150 mL) and a mean operation time of 95.16 ± 20.31 min (60–180 min). According to the Eden classification, there were four type II cases, 16 type III cases, and 11 type IV cases. The incidence of tumors in the lower thoracic segment (T8–T12) was 51.6% (16/31 cases), while the incidences in the upper thoracic segment (T1–T4) and middle segment (T5–T8) were 25.8% (8/31 cases) and 22.6% (7/31 cases), respectively. Pathological diagnoses were schwannoma (n = 22), gangliocytoma (n = 4), metastatic tumor (n = 2), neurofibroma (n = 1), granuloma (n = 1), and lipoma (n = 1). After surgery, symptoms were relieved in all patients. VAS and JOA scores significantly improved (P < 0.001). There was no pleural or lung injury, and there were no complications, such as cerebrospinal fluid leakage. The average follow‐up duration was 29 months (13–59 months), during which time no tumor recurrence or spinal instability occurred. The group of Eden type II tumors had lower JOA scores at 12 months postoperatively, longer operation times, and more estimated blood loss compared with other groups (P < 0.05). There were no significant influences on VAS scores at 12 months postoperatively and postoperative hospital stay from the different types of tumors.ConclusionThe paravertebral approach with a micro‐tubular technique is a safe and effective minimally invasive surgical approach for thoracic dumbbell tumors that allows one‐stage tumor resection using a single incision. Using this approach significantly reduces intraoperative blood loss and postoperative complications, shortens hospital stay, and reduces the rates of postoperative spinal instability.     

Lateral Temporal Bone Resection in Advanced Cutaneous Squamous Cell Carcinoma: Report of 35 Patients

Objective To evaluate lateral temporal bone resection (LTBR) in the management of advanced cutaneous squamous cell carcinoma (SCC) with temporal bone invasion and patterns of failure.Methods This is a retrospective study of 35 patients undergoing lateral temporal bone resection for advanced cutaneous SCC at a tertiary care center between 1995 and 2006.Results The Pittsburgh tumor stage was T4 in 18 patients (51%), T3 in 5 (14%), T2 in 9 (26%), and T1 in 3 (9%). Clear margins were reported in 22 (63%) patients. Resection of the mandible and/or temporomandibular joint (TMJ) was required in 11 (31%) patients. Facial nerve involvement was seen in 10 (29%) patients. Survival outcomes at 2 and 5 years for overall survival were 72% and 49%; disease-free survival, 68% and 59%; and disease-specific survival, 79% and 62%, respectively. Pittsburgh T stage correlated significantly with disease-specific survival (p = 0.015) and margin status was significant for both disease-free survival (p = 0.0015) and disease-specific survival (p < 0.001).Conclusions Surgery with curative intent is justified for cutaneous SCC invading the temporal bone with extended LTBR. Margin status was a significant predictor of outcome. Surgeons should plan preoperatively to achieve clear margins by extending the LTBR with possible nerve resection.     

Salivary Gland NUT Carcinoma with Prolonged Survival in Children: Case Illustration and Systematic Review of Literature

NUT (midline) carcinoma is a rare, highly aggressive, poorly differentiated carcinoma that characteristically harbors a rearrangement of the NUTM1 gene. Most of these tumors occur in adolescents and young adults, arise from the midline structures of the thorax, head, and neck, and are associated with extremely poor outcomes. Rare cases originating from salivary glands have been reported with clinicopathologic features comparable to NUT carcinoma of other sites. Outcome studies regarding this subgroup are currently lacking. We report a case of NUT carcinoma arising in a submandibular gland of a 12-year-old boy. Diagnosis was confirmed by fluorescence in situ hybridization demonstrating fusion of the BRD4 (19p13.12) and NUTM1 (15q14) gene loci. A systematic review of all previously reported salivary gland NUT carcinomas (n = 15) showed exclusive occurrence of pediatric cases (n = 6) in males compared to adult patients (n = 9, male: female = 1:2; p < 0.05). The median survival was 24 and 4 months for pediatric and adult patients, respectively (95% confidence interval was 8–24 and 1–7 months, respectively; p < 0.01). The 1-year overall survival was 67% for pediatric and 11% for adult patients. Among all NUT carcinomas, pediatric salivary gland tumors may represent a distinct clinical subset associated with male predilection and comparatively prolonged survival.     

EGFR Protein Expression Relates with Tumor Histology,Methylation Status of EGFR and HPV16 E6 Viral Load in Oropharyngeal Carcinoma

The epidermal growth factor receptor (EGFR) pathway is important in tumorigenesis of oropharyngeal carcinoma (OPC). However, the molecular mechanisms contributing to EGFR expression in OPC are not well-known. To detect relating factors and clinicopathological impact of EGFR protein expression in OPC, gene amplification/loss, point mutations including synonymous mutations, and promoter methylation of EGFR, and the viral genome load of human papillomavirus type 16 (HPV16)-E5, -E6, and -E7, after extracting HPV16-related OPCs with qPCR of HPV16-E6 and E7, were investigated in 74 OPC surgical cases, including 52 HPV-related (HPV-OPC) and 22 HPV-unrelated (nHPV-OPC). Immunohistochemical (IHC) data of EGFR expression (high, weak, and negative), validated by the qPCR of EGFR mRNA, were compared with molecular, viral, and clinicopathological data of patients. All nHPV-OPC cases were EGFR-IHC-high, whereas 21.2%, 65.4%, and 13.5% of HPV-OPC cases showed EGFR-IHC-high, -weak, -negative (p < 0.01), respectively. In HPV-OPC cases, EGFR-IHC-weak/negative status was related to promoter methylation of EGFR (p = 0.009), but not with gene amplification/loss or the point mutation of EGFR and was more often seen in HPV16-OPC cases (p = 0.049). Among HPV16-OPC cases, EGFR-IHC-weak/negative was related to high E6 expression. EGFR protein-loss was related to the tumor histology of non-keratinizing squamous cell carcinoma (SCC) (p = 0.035) but not with patient prognosis. In conclusion, decreased EGFR protein expression was more frequent in HPV-OPC than in nHPV-OPC and was related to EGFR methylation, infection of HPV16, and the viral genome load of HPV16-E6. Clinicopathologically, it was related to the tumor histology of non-keratinizing SCC.Supplementary informationThe online version of this article (10.1007/s12105-020-01261-w) contains supplementary material, which is available to authorized users.     

Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12105-021-01335-3.     

The role of near‐infrared fluorescence imaging with indocyanine green dye in pedicle division with the paramedian forehead flap

The paramedian forehead flap is considered the gold standard for nasal reconstruction following oncologic surgery. During the 21‐day delay in two‐stage surgery protocols, many patients report considerably reduced quality of life because of the pedicle. This prospective case series study examined the usefulness of near‐infrared (NIR) fluorescence with indocyanine green (ICG) for flap perfusion assessment and identified variables associated with time to flap perfusion. Ten patients (mean age 75.3 ± 11.6 years) with diagnosis of basal cell carcinoma (n = 9) or squamous cell carcinoma (n = 1) underwent intravenous indocyanine injection and NIR fluorescence imaging for assessment of flap vascularisation 2 to 3 weeks after stage 1 surgery. NIR fluorescence imaging showed 90% to 100% perfusion areas in all patients after 14 to 21 days. Early pedicle division occurred in two patients on postoperative days 14 and 16. One minor complication (wound healing disorder) was seen following flap takedown after 14 days. There were no associations between time to flap perfusion and defect size or flap area. NIR fluorescence imaging with ICG dye is a useful method for non‐invasive perfusion assessment when used in conjunction with clinical assessment criteria. However, a decision for early pedicle division may raise risk of complications in specific patient groups and must therefore be made with great care.     

Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression

Peripheral localisation of papillary thyroid microcarcinoma (PTMC), in comparison with intraparenchymal PTMC (i-PTMC) is related to some clinicopathological features related with biological aggressiveness, including lymph node metastasis (LNM). The expression of PD-L1 in tumour cell has been associated with increased tumour survival, progression, and potentially an aggressive clinical course. This study evaluates the relation between clinicopathological features of PTMC, including tumour localisation, with PD-L1 immunoexpression. The study included 99 patients with the histological diagnosis of PTMC (≥ 5 mm). PD-L1 protein expression was assessed by immunohistochemistry. PTMCs were divided into the four following groups: G1– peripherally localised PTMC (p-PTMC) with PD-L1 expression; G2–p-PTMC without PD-L1 expression; G3–i-PTMC with PD-L1 expression and G4–i-PTMC without PD-L1 expression. G1 was the most frequent (n = 46; 46.5%), followed by G4 (n = 25; 25.3%) and similar distribution of G3 (n = 15; 15.2%) and G2 (n = 13; 13.1%). In comparison with other groups, G1 was significantly associated with classical morphology, invasive growth, lymphatic invasion (LI), vascular invasion (VI), psammoma bodies, intratumoral fibrosis, PD-L1 positive tumour-infiltrating lymphocytes, and multinuclear giant cells (MGCs). G4 more commonly exhibited follicular morphology, expansive/circumscribed growth, and absence of the following: intratumoural fibrosis, LI, VI, psammoma bodies, PD-L1 positive tumour-infiltrating lymphocytes, and MGCs. LNMs were significantly more frequent in G1 in comparison with the other groups (p = 0.000). In conclusion, morphology and tumour microenvironment of p-PTMC with PD-L1 expression is different from i-PTMC without PD-L1 expression. The differences between these two groups of PTMC include clinicopathological features related with biological aggressiveness such as the occurrence of LNM.