Atypical Mitoses Research Articles

PSAT017 A Case of Aldosterone- and Cortisol Co-secreting Adrenal Corticol Neoplasm with Lipomatous and Myeiolipomatous Metaplasia

Abstract Background Adrenal lipomatous tumors are uncommon fatty tumors of theadrenal glands with myelolipoma being the most common histologic feature.Adrenal myelolipoma is a benign adrenal cortical neoplasm composed of fat andmyeloid tissue, commonly diagnosed if fat composition of tumor is more than 50% on cross-sectional imaging studies. The myelolipomatous metaplasia is asecondary degenerative change in primary adrenal tumor, usually seen in benignadrenocortical adenomas and rarely in adrenocortical carcinomas and corticalneoplasms of uncertain malignant potential. Adrenocortical neoplasms areclassified as benign or malignant based on modified Weiss score, when the criteriaare not clear, the tumor is classified as a neoplasm of uncertain malignant lesion.As adrenal lipomatous tumors are usually benign and non-functional, patients withthese tumors often do not undergo hormonal evaluation. Clinical Case A 58-year-old female with a history of hypertension diagnosed atage 35 years, on five antihypertensive agents and a history of intermittentspontaneous hypokalemia, was found to have a 6 cm left adrenal myelolipoma onnon-contrast computed tomography of the abdomen performed when she presentedfor left flank pain due to nephrolithiasis. The biochemical evaluation showedpotassium of 2.8 meq/l, plasma aldosterone of 65.9 ng/dl with plasma renin activityof 0.1 ng/ml/hr. An overnight 1 mg dexamethasone suppression test showed nonsuppressible serum cortisol of 10.8 μg/dl. DHEAS, and ACTH were measured at24.5 μg/dl and <5 pg/ml, respectively. Left adrenalectomy was performed and onthe following day, morning serum cortisol was 2.3 μg/dl with aldosterone of 6.2ng/dl and plasma renin activity of 4.2 ng/ml/hr. Expectedly patient beganexperiencing nausea, and postural dizziness. Patient systolic blood pressure was inlow100 mmHg. Thus, hydrocortisone therapy was initiated. Immediatelypostoperatively and thereafter, her blood pressure was controlled with noantihypertensive agent, and morning cortisol measured without hydrocortisone for∼36 h remained low at 1.2 μg/dL. Pathology showed adrenal cortical neoplasm ofuncertain malignant potential with associated lipomatous and myelolipomatousmetaplasia without atypical mitoses, or lymphovascular invasion, or necrosis, orcapsular invasion, with negative surgical margins. Although mitotic activity in thetumor is lacking, the tumor was designated uncertain malignant potential due to thelarge size (7 cm), and lack of clear cells < 25% according to modified Weiss score. Conclusion We report a rare case of aldosterone and cortisol co-secreting adrenalcortical neoplasm of uncertain malignant potential with lipomatous andmyelolipomatous metaplasia. While the majority of cases of myelolipoma arebenign and non-functioning, this case emphasizes the importance of looking forsymptoms and signs pointing to adrenal hyperfunction, thorough hormonal andmorphologic evaluation and, definitive treatment is curative unilateraladrenalectomy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The characteristics and clinical significance of atypical mitosis in breast cancer

AbstractAtypical mitosis is considered a feature of malignancy, however, its significance in breast cancer (BC) remains elusive. Here, we aimed to assess the clinical value of atypical mitoses in BC and to explore their underlying molecular features. Atypical and typical mitotic figures were quantified and correlated with clinicopathological variables in a large cohort of primary BC tissue sections (n = 846) using digitalized hematoxylin and eosin whole-slide images (WSIs). In addition, atypical mitoses were assessed in The Cancer Genome Atlas (TCGA) BC dataset (n = 1032) and were linked to the genetic alterations and pathways. In this study, the median of typical mitoses was 17 per 3 mm2 (range 0–120 mitoses), while the median of atypical mitoses was 4 (range 0–103 mitoses). High atypical mitoses were significantly associated with parameters characteristic of aggressive tumor behavior. The total number of mitoses, and a high atypical-to-typical mitoses ratio (>0.27) were associated with poor BC specific survival (BCSS), (p = 0.04 and 0.01, respectively). The atypical-to-typical mitoses ratio dichotomized triple negative-BC (TNBC) patients into two distinct groups in terms of the association with the outcome, while the overall number of mitoses was not. Moreover, TNBC patients with high atypical-to-typical mitoses ratio treated with adjuvant chemotherapy were associated with shorter survival (p = 0.003). Transcriptomic analysis of the TCGA-BRCA cohort dichotomized based on atypical mitoses identified 2494 differentially expressed genes. These included genes linked to pathways involved in chromosomal localization and segregation, centrosome assembly, spindle and microtubule formation, regulation of cell cycle and DNA repair. To conclude, the atypical-to-typical mitoses ratio has prognostic value independent of the overall mitotic count in BC patients and could predict the response to chemotherapy in TNBC.

S1686 Primary Pancreatic Diffuse Large B Cell Lymphoma: A Rare and TreaTable Malignancy

Introduction: Pancreatic lymphoma comprise less than 1 % of pancreatic malignancies. Most common location of diffuse large B cell lymphoma (DLBCL) are lymph nodes. Clinical symptoms and imaging studies have significant similarity resulting in delayed diagnosis or early initiation of comfort care measures. It is important to determine the histology of pancreatic tumor given the differences in management and prognosis. Here we report a rare case of primary DLBCL arising from pancreas. Case Description/Methods: 62-year-old female with history of HTN and DM presented with 30 lbs unintentional weight loss epigastric abdominal pain and early satiety. CT abdomen with IV and oral contrast demonstrated pancreatic mass. Core biopsy of pancreatic head mass demonstrated infiltration by large atypical lymphoid cells with high N/C ratio, round nuclear contour, fine chromatin and variably prominent nucleoli (Figure A). Atypical mitosis and apoptosis seen in background. Lymphoma cells positive for CD 19, CD 20 (Figure B). Final diagnosis Large B cell lymphoma germinal center type. FISH for BCL 2, C MYC were normal ruling out possibility of double or triple hit lymphoma. Cancer antigen 19-9 at the time of diagnosis was within normal limits. FDG PET/CT prior to initiation of treatment showed main foci of increased tracer activity appears to be in the proximal body of the pancreas just medial to the stomach, measures greater than 4 cm in diameter, and has a maximum SUV of 11.86 (Figure C). Rituximab- Cyclophosphamide HydrOxyadriamycin Prednisone (R-CHOP) every 3 weeks initiated. After one cycle of R-CHOP reported significant improvement in epigastric pain and started gaining weight. She completed 6 cycles of R-CHOP. Post treatment FDG PET/CT complete resolution of upper abdominal lymph node mass (Figure D). She remains in remission for the past 1 year. Discussion: Our case is an example of successful biopsy and treatment with aim to cure pancreatic malignancy. Despite radiological differences between pancreas adenocarcinoma and lymphoma, it is crucial to obtain adequate tissue sampling during from pancreas to establish histological diagnosis prior to discussion of prognosis and treatment plan. In general, DLBCL germinal center type has a 5-year survival of 70% with R-CHOP. Differential diagnosis of pancreatic mass that confer better prognosis than adenocarcinoma include neuroendocrine tumor, solid pseudopapillary tumor and lymphoma. Therefore, it is important to obtain biopsy and direct therapy based on histology.Figure 1.: A: Core biopsy of pancreatic head mass demonstrated infiltration by large atypical lymphoid cells with high N/C ratio, round nuclear contour, fine chromatin and variably prominent nucleoli. B: Lymphoma cells positive for CD 19, CD 20. C: FDG PET/CT prior to initiation of treatment showed main foci of increased tracer activity appears to be in the proximal body of the pancreas just medial to the stomach, measures greater than 4 cm in diameter, and has a maximum SUV of 11.86. D: Post treatment FDG PET/CT complete resolution of upper abdominal lymph node mass.

♣Evaluation of clinicopathological profiles and development of a risk model in renal epithelioid angiomyolipoma patients: a large-scale retrospective cohort study

BackgroundTo identify the malignant potential and prognostic indicators of renal epithelioid angiomyolipoma (eAML), clinicopathological and molecular features as well as the drug efficacy of 67 eAML cases were analyzed.Materials and methodsSixty-seven renal eAML patients were enrolled and the immunohistochemical features of these patients were examined. FFPE slides of all patients were re-examined. 21 patients with metastasis received Everolimus 10 mg orally once daily. Responses were evaluated with RECIST criteria by three authors. A risk stratification model was constructed using the following factors: pT3 and pT4, presence of necrosis, mitotic count ≥ 2; the presence of atypical mitoses; severe nuclear atypia, SMA negative, Ki-67 ≥ 10%.ResultsThe average percentage of the epithelioid component was 85.6% (range 80–95%). Immunohistochemically, Ki-67 ≥ 10% and negative SMA staining were significantly correlated with malignant characteristics (Ki-67: p < 0.001; SMA: p = 0.001). Survival analysis suggested that pT3-pT4 stage, presence of necrosis, severe nuclear atypia, presence of atypical mitoses, mitotic count ≥ 2, Ki-67 ≥ 10% and negative SMA expression were significantly associated with poorer PFS and OS (p < 0.05). The risk model sufficiently discriminated recurrence/metastasis (AUC = 0.897) and cancer-specific mortality (AUC = 0.932) of renal eAML patients in different risk groups. 21 patients had received Everolimus targeted therapy after recurrence/metastasis. The best response for Everolimus treatment was 8/21 (38.1%) partial responses (PR), 9/21 (42.9%) stable disease (SD) and 4/21 (19.0%) progressive disease (PD).ConclusionThe risk stratification model could well distinguish eAML patients at high risk of recurrence/metastasis. Everolimus targeted treatment showed good efficacy in patients with recurrence/metastasis.

Histomorphological and Demographic Profile of Breast Carcinoma in Anatomical Pathology Department FKUI/RSCM 2016-2019

BackgroundInvasive breast carcinoma (IBC) is the most commonly diagnosed cancer in woman in the world and Indonesia. IBC is classified into two main categories: IBC of no special type (NST) and special types. This retrospective study aims to provide histomorphological profile of mastectomy cases of IBC in Anatomical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital (PA FKUI/RSCM) 2016-2019.MethodsThis is a descriptive research with cross-sectional design of mastectomy cases, using secondary data from the archives of PA FKUI/RSCM, starting from 2016- 2019. Collecting clinical data as well as observing several histopathologic parameters including histological type, grade, atypical mitotic features, lymphovascular invasion, and lymph node metastases. Tumour classification was made based on the WHO breast criteria in 2019.ResultsDuring the 2016-2019 period there were 144 cases of IBC. 99.3% of cases occurred in female patients, mostly in the age group from 40 to 59 years and unilateral. The majority had tumour sizes ranging &gt;2-5 cm and were stage II. About a third of cases had received neoadjuvant chemotherapy, most commonly in advanced local stage tumors. Most histologic type (65.3%) were IBC of NST and 52.8% of cases were grade 2. There were 92 (63.4%) cases with atypical mitotic features, most commonly found in stage III. Lymphovascular invasion was found in 38.9% of cases and lymph node metastasis was found in 63.2% of cases.ConclusionIBC is the most common cancer in woman, with the most common histologic type were IBC, grade 2, stage II or more. Most of the cases show atypical mitosis, which is most commonly found in stage III. The findings of lymphovascular invasion did not always coincide with the findings of lymph node metastases.

Secretory carcinoma of the salivary gland: a multi-institutional clinicopathologic study of 90 cases with emphasis on grading and prognostic factors.

A detailed clinicopathologic review was conducted on 90 SCs from the major and minor salivary glands. The median age at presentation was 50 years (range: 7-93). Sixty-nine (77%) tumours originated from major salivary glands, whereas the remaining 21 involved minor salivary glands.Six cases (7%) had cervical nodal metastasis. Only lymphovascular invasion (LVI) was associated with a risk of nodal metastasis (P < 0.05). The 5-year disease-specific survival and disease-free survival (DFS) were 98% and 87%, respectively. On univariate survival analysis, adverse prognostic factors associated with decreased DFS included minor salivary gland origin, atypical mitosis, high mitotic index, high-grade transformation (HGT), necrosis, nuclear pleomorphism, infiltrative tumour border, fibrosis at the invasive front, LVI, positive margin, and advanced pT stage (P < 0.05). When adjusted for pT stage and margin status, mitotic index, LVI, nuclear pleomorphism, and HGT remained as independent prognostic factors. We therefore propose a two-tiered grading system for SC. The low-grade SC is defined as those with <5 mitoses /10 high-power fields and no tumour necrosis, and high-grade SC as those with ≥5 mitoses /10 high-power fields and/or necrosis. This proposed grading system can be useful to risk stratify patients with SC for appropriate clinical management.

ORAL SQUAMOUS CELL CARCINOMA WITH MANDIBULAR BONE INVASION: CASE REPORT

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. Bone invasion by OSCC can have different clinical behavior and a variable prognosis. A 58-year-old man was referred to the Dental Specialties Center with complaint of a rapidly developing oral wound. On intraoral examination, leukoplakia associated with ulcerated areas on the lateral tongue and lower right alveolar ridge was observed. Computed tomography revealed a hypodense and infiltrative lesion in the mandibular bone and disruption of the cortical bone. After biopsy, microscopic examination showed malignant epithelial neoplasia composed of islands of neoplastic cells with intense pleomorphism, nuclear hyperchromatism, atypical mitoses, and prominent nucleoli. The final diagnosis of OSCC with mandibular bone invasion was obtained. The patient underwent surgical resection with an adequate tumor margin and neck dissection. Currently, the patient is in follow-up without recurrence. Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. Bone invasion by OSCC can have different clinical behavior and a variable prognosis. A 58-year-old man was referred to the Dental Specialties Center with complaint of a rapidly developing oral wound. On intraoral examination, leukoplakia associated with ulcerated areas on the lateral tongue and lower right alveolar ridge was observed. Computed tomography revealed a hypodense and infiltrative lesion in the mandibular bone and disruption of the cortical bone. After biopsy, microscopic examination showed malignant epithelial neoplasia composed of islands of neoplastic cells with intense pleomorphism, nuclear hyperchromatism, atypical mitoses, and prominent nucleoli. The final diagnosis of OSCC with mandibular bone invasion was obtained. The patient underwent surgical resection with an adequate tumor margin and neck dissection. Currently, the patient is in follow-up without recurrence.

LANGERHANS CELL SARCOMA INVOLVING THE ORAL CAVITY

Langerhans cell sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. Only one previous case has been reported in the oral cavity. A 79-year-old male patient presented for evaluation of multiple lesions affecting the lower lip, hard palate, upper alveolar mucosa, and skin. Biopsy of the lesions affecting the lower lip and palate showed a proliferation of histiocytic cells presenting atypia, pleomorphism, and atypical mitoses. Diagnosis of LCS was supported by immunoreactivity of the neoplastic cells for S-100, CD1a, CD207, and CD83. The patient died from widespread disease 3 months after diagnosis. Due to its rarity, LCS poses a diagnostic problem in the oral cavity and should be considered in the differential diagnosis of histiocytic proliferations.

SARCOMATOID CARCINOMA: A CASE REPORT

Sarcomatoid carcinoma (SC) is an infrequent variant of squamous cell carcinoma. A 62-year-old male patient with a long smoking and drinking history reported difficulty swallowing due to a rapidly growing mass in the floor of the mouth for 5 weeks. Intraorally, an exophytic mass of 2 cm was observed. After biopsy, histopathologic examination revealed a proliferation of neoplastic cells with epithelial differentiation, organized in nests and islands, as well as fascicles of spindle cells, exhibiting intense cellular pleomorphism and the presence of numerous atypical mitoses. Neoplastic cells with epithelial morphology were positive for anti-AE1/AE3 antibody and the spindle cell component strongly positive for vimentin and alpha-SMA. The anti-Ki67 antibody showed 38% of positivity in the epithelial component and 22% in the spindle cell component. The diagnosis of SC was made. The patient underwent chemotherapy but died after 12 months of treatment. Sarcomatoid carcinoma (SC) is an infrequent variant of squamous cell carcinoma. A 62-year-old male patient with a long smoking and drinking history reported difficulty swallowing due to a rapidly growing mass in the floor of the mouth for 5 weeks. Intraorally, an exophytic mass of 2 cm was observed. After biopsy, histopathologic examination revealed a proliferation of neoplastic cells with epithelial differentiation, organized in nests and islands, as well as fascicles of spindle cells, exhibiting intense cellular pleomorphism and the presence of numerous atypical mitoses. Neoplastic cells with epithelial morphology were positive for anti-AE1/AE3 antibody and the spindle cell component strongly positive for vimentin and alpha-SMA. The anti-Ki67 antibody showed 38% of positivity in the epithelial component and 22% in the spindle cell component. The diagnosis of SC was made. The patient underwent chemotherapy but died after 12 months of treatment.

Interobserver variability in the diagnosis of canine hepatoid gland tumors

The reported prevalence of canine hepatoid gland tumor (HGT) varies widelyowing mainly to the lack of well-defined diagnostic criteria and poor interobserver agreement. The aim of the present study was to improve the level of diagnostic agreement among pathologists in canine HGT. Five pathologists diagnosed and classified morphological features in 57 cases of canine HGT and, based on their reports, diagnostic algorithms were devised using recursive partitioning analysis. The proportion of diagnoses of malignant hepatoid neoplasia among the five pathologists ranged from 26.3 to 50.9%. Interobserver diagnostic agreement was classified as fair (κ=0.54) but improved to good (κ~0.65) following application of two novel diagnostic algorithms based on histomorphological features as sebaceous differentiation, mitotic count, atypical mitosis and cellular atypia. This study has demonstrated that interobserver agreement in the diagnosis of canine HGT could be improved using novel algorithms. Further analyses are warranted to validate the proposed classification systems applying a higher sampling of canine HGTs.

Usefulness of squash preparation cytology in the diagnosis of canine urinary bladder carcinomas.

Epithelial cells show varying degrees of cytologic atypia in dogs with nonmalignant lesions (NML) and carcinomas (ubC) of the bladder, making histopathologic examination necessary for a definitive diagnosis. This study aimed to investigate the diagnostic performance of squash preparation cytology and identify several cytomorphologic features of ubC to assist in diagnoses. Squash preparations were made and reviewed in dogs that underwent transurethral cystoscopy. The results were compared with histopathologic diagnoses. Two cytopathologists performed blinded assessments using a scoring system established for 11 cytologic features, including the presence of macronuclei, abnormal nucleoli, atypical mitoses, signet ring cells, multinucleated cells, nuclear molding, anisokaryosis, cytoplasmatic microvacuolization, cell arrangements, and neutrophil and lymphocyte infiltrations. Based on cytologic and histopathologic diagnoses, dogs were divided into ubC and NML groups. Associations between cytologic and histopathologic diagnoses were investigated, and agreement between the cytopathologists was calculated. Cytologic features were analyzed with multivariate logistic regression models. The performance of predictors in the final model was evaluated in terms of Sensitivity (Se), Specificity (Sp), accuracy, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio positive (LR+), and negative (LR-) values, and the diagnostic odds ratio (DOR). Forty-four dogs diagnosed with ubC, and 17 with NML were included in the study. Cytologic and histopathologic diagnoses were significantly associated with each cytopathologist. There was an almost perfect agreement between cytopathologists (κ=0.88). The absence of neutrophilic infiltration, the presence of multinucleated cells, and nuclear molding were associated with ubC; using a combination of these features in parallel testing resulted in Se=0.98, Sp=0.65, accuracy=0.89, PPV=0.88, NPV=0.92, LR + =2.77, LR-=0.04, and DOR=7.7. Squash preparation cytology could be a reliable technique to diagnose ubC in dogs. The best diagnostic combination was the absence of neutrophilic infiltration, multinucleated cells, and nuclear molding.

Cytomorphological spectrum of solitary fibrous tumour: revisited.

Solitary fibrous tumour (SFT) is a tumour of mesenchymal origin. Its diagnosis on cytology is challenging, owing to variation in cellularity, sparsely distributed cellular and stromal components. Cytomorphological findings for this type of tumour have rarely been described in the literature-only a few case reports and the occasional case series have been presented thus far. We present the cytomorphological features of SFT with special emphasis on immunochemical findings. We present cytological data from eight cases of histopathologically proven SFTs. The cytomorphological features, immunochemical markers and differential diagnostic entities on fine needle aspiration cytology are discussed. Fine needle aspiration was performed at various anatomical sites. Cytology smears showed variable cellularity, with tumour cells arranged in loose clusters and as singly scattered cells. Interlacing fascicles with palisading of cells was noted. The cells were predominantly spindle to elongated, having moderate cytoplasm with elongated wavy nuclei. These nuclei had fine to coarse chromatin, with inconspicuous to prominent nucleoli. There was prominent, metachromatically staining, amorphous to fibrillary, collagenous to myxoid matrix material associated with the tumour cells. Other findings included intranuclear pseudo-inclusions, multinucleated giant cells and atypical mitoses. Cytological diagnoses offered varied from 'spindle cell neoplasm' to 'spindle cell sarcoma' or 'suggestive of sarcoma'. Immunocytochemistry (ICC) performed on cell block sections showed positivity for STAT6, CD34 and Bcl-2. Cytological diagnosis of SFT can be challenging. A careful search for characteristic cytomorphological features is diagnostically helpful. The cytomorphology should be interpreted with caution, with an appropriate ICC panel, including STAT6 and CD34.

Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma

Objective: To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma. Methods: The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results: (1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions: FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.

Histopathological and Immunohistochemical Appearance of Pleomorphic Dermal Sarcoma

Pleomorphic dermal sarcoma is a rare and aggressive entity that originates in the skin’s dermis. This poorly defined tumor usually appears on the sun exposed skin of the elderly and involves the male gender more often. We describe the case of a 54 year old male patient who presented to the Surgery Department with a tumor located on the scalp. Surgery was performed and the sample was sent to the Pathology Department of Mures Clinical County Hospital for further analysis. Histological analysis showed a tumor with solid architecture and nesting phenomenon, composed of pleomorphic epithelioid cells with high atypia. Typical and atypical mitoses were observed. Immunohistochemistry showed positivity for the following markers: vimentin, CD68 and ki67- proliferation value of 90%. The cells were negative to CK AE1/AE3, S100, SOX10, HMB45, MelanA, CD31, Desmin and SMA. In conclusion, pleomorphic dermal sarcoma represents a challenging diagnosis. The case highlights the histological and immunohistochemistry appearance of the neoplasm. Due to the local aggressivity, difficulty in providing negative resection margins and uncertain prognosis, it’s important to take this entity into consideration each time we encounter a cutaneous pleomorphic tumor.

A novel morphology-based risk stratification model for stage I uterine leiomyosarcoma: an analysis of 203 cases

AbstractUterine leiomyosarcoma is the most common uterine mesenchymal malignancy. The majority present at stage I, and clinical outcomes vary widely. However, no widely accepted risk stratification system for stage I uterine leiomyosarcoma is currently available. We studied 17 routinely evaluated clinicopathologic parameters in 203 stage I uterine leiomyosarcoma from three institutions to generate a novel risk stratification model for these tumors. Mitoses >25 per 2.4 mm2 (10 high-power fields), atypical mitoses, coagulative necrosis, lymphovascular invasion, and serosal abutment were significantly associated with disease-free and disease-specific survival in univariate and multivariate analyses. These prognostic parameters were each scored as binary (“yes” or “no”) variables and fitted to a single optimized algebraic risk model:Risk score = (coagulative necrosis)(1) + (mitoses > 25 per 2.4 mm2)(2) + (atypical mitoses)(2) + (lymphovascular invasion)(3) + (serosal abutment)(5)By logistic regression, the risk model was significantly associated with 5-year disease-free (AUC = 0.9270) and 5-year disease-specific survival (AUC = 0.8517). Internal and external validation substantiated the model. The continuous score (range, 0–13) was optimally divided into 3 risk groups with distinct 5-year disease-free and disease-specific survival: low risk (0–2 points), intermediate risk (3–5 points), and high risk (6–13 points) groups. Our novel risk model performed significantly better than alternative uterine leiomyosarcoma risk stratification systems in predicting 5-year disease-free and disease-specific survival in stage I tumors. A simplified risk model, omitting terms for serosal abutment and lymphovascular invasion, can be accurately applied to myomectomy or morcellated specimens. We advocate routine application of this novel risk model in stage I uterine leiomyosarcoma to facilitate patient counseling and proper risk stratification for clinical trials.

Distinct H3F3A Driver Mutation Defines Giant Cell Tumor of Bone: A Necessary Adjunct in the Diagnosis of Such a Lesion in the Hyoid Bone, Presenting as a Base of Tongue Mass

<h3>Introduction</h3> Giant cell tumor of bone (GCTB) is a rare benign tumor mostly affecting the epiphyses of long bones in skeletally mature patients that is rarely described in the head and neck. Conventionally, diagnosis is based on microscopic features, exclusion of mimics, and clinico-radiologic correlation. Morphologic overlap with numerous giant cell-containing lesions of bone and soft tissue complicates the diagnosis. GCTB is characterized by the <i>H3F3A</i> mutation, which can be detected immunohistochemically using H3.3 G34W, a monoclonal antibody specific for this mutation. <h3>Case Findings</h3> A 57-year-old male presented with dysphagia, dysarthria, and right base of tongue (BOT) mass suspicious for carcinoma. Imaging revealed a heterogeneous parapharyngeal lesion extending from BOT to the hyoid bone. A BOT biopsy demonstrated giant cell-rich granulation tissue and non-endothelial lined blood lakes, suggestive of aneurysmal bone cyst (ABC). Fluorescent in situ hybridization (FISH) analysis did not identify <i>USP6</i> rearrangement, effectively eliminating primary ABC and favoring secondary ABC. Base of tongue resection, partial pharyngectomy and hyoid bone resection followed. <h3>Results</h3> Microscopically, the resection revealed a giant cell-rich lesion emanating from the hyoid bone, suggestive of GCTB and thus unlikely soft tissue giant cell tumor. Cellular pleomorphism and atypical mitoses were absent. Stromal cells expressed H3.3 G34W, confirming the diagnosis of GCTB. Zonal features of secondary ABC were juxtaposed to the dominant GCTB. <h3>Conclusions</h3> Hyoid GCTB is exceedingly rare, and such a diagnosis presents a conundrum. H3.3 G34W nuclear staining is an indicator of <i>H3F3A</i>mutation in GCTB that can help distinguish GCTB from other mimics. Prior reports of hyoid GCTB did not employ ancillary studies to identify <i>H3F3A</i> mutation or <i>USP6</i> rearrangements, as these have only been recently available. Our case fulfills current diagnostic criteria for GCTB, and excludes other giant cell-rich lesions. Accurate diagnosis of GCTB in this atypical location allows for appropriate surveillance algorithms.

A rare primary localized extranodal histiocytic sarcoma of oral mucosa: a case report

<h3>Background</h3> Histiocytic sarcoma is a rare hematopoietic malignancy which typically involves extranodal sites, mainly of the gastrointestinal tract. Of the small number of reported cases in the head and neck region, only one case was localized to the oral cavity. The disease may present as a solitary lesion or disseminated process secondary to other hematopoietic malignancies. Histopathologically, the tumors can be mistaken for other lymphoprolifera- tive disorders. Immunohistochemistry shows tumor cells expressing one or more of the histiocytic markers CD163, CD68, or lysozyme. Surgery with or without chemotherapy or radiotherapy are the mainstays of treatment. Even though histiocytic sarcoma has clinically aggressive behavior with poor response to therapy, studies show that a subset of the patients with localized disease and small tumor size have more favorable outcome with surgery alone. We present a case with localized extranodal histiocytic sarcoma of oral mucosa. <h3>Case Description</h3> A 31-year-old, fe- male with onemonth duration of a 10 × 8 × 2 mm smooth-surfaced, well circumscribed, firm soft tissue enlargement at buccal vestibule of #11/12. Biopsy shows a diffuse population of pleomorphic cells with atypical mitoses and fine granular cytoplasm within fibrocollagenous connective tissue. Immunohistochemical studies demonstrated tumor cells positive to CD163, CD68, CD45, CD43, CD4, muramidase, SOX10, S100, NSE and vimentin with a diagnosis of his- tiocytic sarcoma. Surgical excision with uninvolved margins was performed. The diagnosis of histiocytic sarcoma was confirmed with hematopathology consultation. There was no evidence of tumor recurrence after 3 months fol- low up. <h3>Conclusion</h3> To the best of our knowledge, this is the second case of primary localized extranodal histiocytic sarcoma of oral cavity. Surgery alone was the treatment modality for our case. However, due to the rarity/limited number of reported cases, treatment outcomes of a localized disease is limited. The treatment protocol may become more evident as newer studies emerge.

METASTATIC LEIOMYOSARCOMA OF THE PALATAL GINGIVA MASQUERADING AS A PYOGENIC GRANULOMA

Leiomyosarcoma (LMS) is a smooth muscle neoplasm, accounting for 7% of soft-tissue and 1-4% of head-neck sarco- mas. Oral-LMS is extremely uncommon and may represent primary or metastatic disease. We describe a 46-year- old female with a medical history of "stomach cancer" who presented with a palatal mass. Upon further inquiry, it was discovered that the patient had been diagnosed with high-grade LMS of the retroperitoneum six years prior, which had been treated with radical resection and right nephrectomy followed by post-operative radiation and ad- juvant chemotherapy. She subsequently developed liver metastasis requiring modification of her chemotherapy. However, she had elected to discontinue treatment one year prior to the presentation of the oral lesion. A biopsy of the palatal mass revealed a malignant spindle-cell proliferation expanding the overlying epithelium, with brisk mitotic activity and atypical mitosis, nuclear pleomorphism, and focal areas of tumor necrosis, raising the concern for LMS. Immunohistochemical (IHC) stains for SMA were strongly positive while negative for DOG1 and CD 117. Based on the history and supportive histopathological and IHC findings, a diagnosis of metastatic LMS of the palate was given. Oral metastases of LMS are exceedingly rare and aggressive lesions that arise mostly in females in their sixth-decade. Literature review shows that metastases to the tongue, gingiva, lip, and buccal mucosa are typically associated with primary uterine tumors, while metastasis to the mandibular gingiva is documented frequently with non-uterine primaries. Clinically, lesions can present as a nonspecific painful mass. Microscopic diagnosis is often challenging due to significant overlap with other spindle-cell neoplasms, requiring careful correlation with medical history, physical examination, and ancillary studies. We herein report a rare case of a retroperitoneal LMS that metastasized to the palate. A literature review of metastatic oral-LMS and retrospective institutional analysis of oral metastases will also be presented.

Telomere length was associated with grade and pathological features of meningioma

Telomeres are tandem repeats of the TTAGGG sequence at chromosomal ends and afford protection against chromosomal instability. To investigate the contribution of telomere dysfunction in meningiomas, here we estimate the associations between telomere length, tumor grade, and proliferation index in a series of 14 archived samples, using quantitative-fluorescence in situ hybridization, Ki67 immunostaining, and pathological analysis. The number of mitoses per 10 high-power fields (HPF) and Ki67 index was higher in grade III cases than in grade I or grade II cases. Telomere length was negatively associated with both the number of mitoses/10HPF and Ki67 index. Meningioma cases with atypical mitosis, a morphological marker of chromosomal instability, exhibited shortened telomeres. Among telomere-shortened meningioma cases, 40% were grade I, 20% were grade II, and 100% were grade III. In grade I or II meningiomas, shortened telomeres lacked high proliferation activity and atypical mitosis. In conclusion, telomere shortening might be pivotal in the development of high-grade meningioma. Analysis of telomere length might be a selective marker for meningiomas with high-grade malignant potential.

Endometrial giant cell carcinoma: new insights from a morphological, immunohistochemical, and molecular analysis of three cases.

Herein, we present a morphological, immunohistochemical, and molecular analysis of three cases of endometrial giant cell carcinoma (EGCC) with a literature review. Patient age was 55 to 76years. The tumors were limited to the uterus and showed dyshesive, bizarre giant cells with numerous atypical mitoses. Minor components were low-grade endometrioid, spindled/myxoid (case nos. 1 and 2), serous (case no. 3), and undifferentiated (all cases). The giant cells were e-cadherin-, cytokeratins/EMA + (focal/multifocal), hormone receptors + (focal/multifocal), vimentin + , p16 + (diffuse), CD68-, α-FP-, β-HCG-, muscle markers-, CD10-, and ERG-. Case no. 3 was p53-abnormal. All cases were mismatch repair-proficient and microsatellite-stable. No POLE mutations were detected. Based on our and previous reports, EGCC is often accompanied by a conventional carcinomatous component (mostly endometrioid) and shows partial loss epithelial markers and negativity for specific differentiation markers. EGCC shows evident similarities to both undifferentiated/dedifferentiated carcinoma and carcinosarcoma and should be managed similarly. Unlike the latter two, EGCC might preferentially derive from "no-specific-molecular-profile" carcinomas.