Marked Cytologic Atypia Research Articles

Giant pilomatricoma with atypical features: report of a case of aggressive pilomatricoma in an adult

Abstract Introduction/Objective Pilomatricoma, also known as pilomatrixoma or calcifying epithelioma of Malherbe, is a relatively common, benign tumor of the hair matrix. It typically presents as a small (~1cm), dermal based mass in the head and neck region of children and young adults (under 20 years) with predominance for males, but can occur in any age. In contrast, malignant pilomatricoma is typically larger (1 to 10 cm) and occurs later in life (50-60 years). Aggressive pilomatricoma is a variant of pilomatricoma that tends to occur in children and demonstrates atypical features such as increased matrical cells and nuclear atypia, but insufficient for a classification as pilomatrical carcinoma. Here, we presented a case of a large (14.5 cm) aggressive/atypical pilomatricoma that occurred in an adult. Methods/Case Report A 45 year-old-female presented to the emergency department with a posterior neck mass which has been slowly enlarging for years. Recently, it became painful with sanguineous discharge which prompted her to seek medical attention. CT scan revealed a lobulated, pedunculated mass with fat and fluid components. An excision was performed. Gross examination revealed an ulcerated mass measured 14.5 cm in greatest dimension. Scattered calcifications were present. Microscopically, nests of basaloid cells with scattered shadow cells are present consistent with matrical differentiation. A multinodular growth pattern with central necrosis was evident. Nuclear atypia characterized by prominent nucleoli and nuclear overlapping was identified. Results (if a Case Study enter NA) NA Conclusion Histopathologic criteria to reliably differentiate between benign and malignant pilomatrical tumors are not well-established. Tumor ulceration, asymmetry, irregular borders, multinodular growth pattern, marked cytologic atypia, prominent necrosis, lymphovascular invasion, and perineural invasion may be used in favor of malignancy. Our case showed focal confluent necrosis, ulceration, multinodular growth pattern, and cellular atypia but lacked other features that indicative of unequivocal malignancy. The resection margins were negative for tumor. Clinical followup was negative for signs of recurrence or metastasis after two years. We presented this case to show the large size that aggressive pilomatricoma can reach and to emphasize the difficulty in differentiating benign from malignant pilomatrical tumors in borderline cases.

Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases.

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria. This validation study included 136 borderline (borderline phyllodes tumor [BoPT]) and MPT cases that were not included in the initial study. We evaluated tumor classifications based on both the Refined Criteria and the WHO criteria. The Refined Criteria defines MPT when these criteria are met (1) stromal overgrowth with ≥ 1 feature(s) of marked stromal cellularity, marked stromal cytologic atypia, or ≥10 mitoses per 10 high-power fields (10 mitoses/10 HPFs) or (2) marked stromal cellularity with ≥1 feature(s) of marked stromal cytologic atypia, ≥10 mitoses/10 HPFs or permeative border. The WHO criteria require all 5 morphologic features (stromal overgrowth, permeative border, marked stromal cellularity, marked stromal cytologic atypia, and ≥10 mitoses/10 HPFs) for an MPT diagnosis. Using the Refined Criteria, none of the 61 BoPTs developed metastasis and 40.0% of the 75 MPTs developed metastases; local recurrence was seen in 11.5% BoPTs and 25.3% MPTs. Using the WHO criteria, 9.6% of the 94 BoPTs developed metastases and 50.0% of the 42 MPTs developed metastases; 14.9% of the BoPTs had local recurrence and 28.6% of the MPTs had local recurrence. Nine (30.0%) of the 30 tumors that developed distant metastases were diagnosed as BoPTs by the WHO criteria. When we combined the 75 MPTs from this validation cohort with the 65 MPT cases from the published data using the Refined Criteria, 50 (35.7%) of the 140 MPTs developed metastases, whereas 8 cases with metastases were <5 cm. In the univariate analysis with log-rank test, stromal overgrowth, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses/10 HPFs, presence of heterologous components other than liposarcomatous component, and presence of stromal necrosis were significantly associated with the risk of metastasis (all with P < 0.05). In multivariate analysis with Cox proportional hazard regression, stromal overgrowth and marked stromal cellularity were significantly associated with metastasis (both with P < 0.001). The Refined Criteria are superior to the WHO criteria in predicting the clinical outcomes of BoPTs and MPTs. Using the Refined Criteria, 35.7% of 140 patients with MPT developed metastases, whereas none (0%) of the patients with BoPT developed metastases. Patients with MPT have a high metastatic rate; these patients may benefit from systemic chemotherapy or targeted therapies. In contrast, patients with BoPT may be managed with complete local excision alone without chemotherapy.

Renal Cell Carcinoma with Sarcomatoid and Rhabdoid Dedifferentiation: Clinico Pathological Significance- Review

Introduction Sarcomatoid and/or rhabdoid dedifferentiation are rare histopathological findings which may be heterogeneous in renal cell carcinoma. Sarcomatoid renal cell carcinoma shows marked cytologic atypia and containing enlarged pleomorphic and malignant spindle cells reminiscent of sarcoma. It is highly aggressive with a high metastatic potential and extremely poor prognosis. Case report A 78-year-old male presented with complaints hematuria, pain abdomen, burring maturation of 2 months duration. The patient had a history of hypertension and diabetes mellitus. Computed tomography revealed a well-defined lobulated, exophytic ball-type, isodense lesion, measuring (~ 7.8 x 7.5 x 11.0 cm) arising from mid and lower poles of right kidney involving renal sinus. Features were suggestive of renal cell carcinoma. The patient underwent a right radical nephrectomy. On histopathological findings reported as clear cell RCC, sarcomatoid and rhabdoid dedifferentiation, Fuhrman grade IV. There was no evidence of any metastasis. The immunochemistry was positive for Paired box 8 (PAX8), Carbonic anhydrase 9 (CA9). The BAP1: BRCA1 Associated Protein-1 was retained. Conclusion-Herewith present an uncommon case of highly aggressive tumor clear cell RCC sarcomatoid and rhabdoid differentiation for its clinical, radioimaging, histopathological and immunohistochemitry significance with review.

Isolated intraductal carcinoma of the prostate: a clinicopathological and molecular analysis

Objective: To study the clinicopathological features, immunohistochemical phenotypes, molecular changes, differential diagnosis and prognosis of isolated intraductal carcinoma of the prostate (iIDC-P). Methods: Three iIDC-P cases were collected retrospectively from 2016 to 2022 at Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinicopathologic features and immunophenotypic profiles were studied using light microscopy and immunohistochemistry. A targeted next-generation sequencing panel was used to analyze cancer-associated mutations. Follow-up and literature review were also performed. Results: The patients' ages were 61, 67 and 77 years, and their preoperative prostate specific antigen (PSA) levels were 7.99, 7.99 and 4.86 μg/L, respectively. Case 1 and 2 were diagnosed on needle biopsy and radical prostatectomy (RP) specimens, and case 3 was diagnosed on a specimen of transurethral resection of the prostate (TURP). The RP specimen was entirely submitted for histologic examination. In the case 1, iIDC-P was found in one tissue core (involving two ducts) in the biopsy specimen, and in 6 sections (diameter, 0.3-1.1 cm) from the radical prostatectomy specimen, and one section had separate foci of low-grade acinar adenocarcinoma (diameter, 0.05 cm). In the case 2, 6 tissue sections from the biopsy specimens showed iIDC-P, and 13 sections from RP specimen showed iIDC-P (diameter, 0.5-1.6 cm), and the other 3 sections had separate low grade acinar adenocarcinoma (diameter, 0.6 cm). In the case 3, 5 tissue blocks from the TURP specimen showed iIDC-P. The case 1 and 2 showed solid architecture with expansile proliferation of neoplastic cells in native ducts and acini. The case 3 showed dense or loose cribriform pattern, with marked cytological atypia, and frequent mitotic figures. Comedonecrosis was found in solid or dense cribriform glands in the case 2. Immunohistochemically, surrounding basal cells were highlighted using high-molecular-weight cytokeratin (34βE12 and CK5/6) and p63, while P504s was positive in the tumor cells. The tumor cells were also positive for AR and prostate markers (NKX3.1, PSA and PSAP), and negative for GATA3. The iIDC-P and acinar adenocarcinoma both showed weak PTEN expression and no ERG (nuclear) expression. In case 2 and 3, targeted sequencing revealed activated oncogenic driver mutations in MAPK and PI3K pathway genes (KRAS, MTOR and PTEN). In addition, pathogenic mutation in TP53 and FOXA1 mutation were found in the case 2 and 3, respectively. No case demonstrated TMPRSS2::ERG translocation. All cases were microsatellite stable and had lower tumor mutation burdens (range, 2.1-3.1 muts/Mb). The patients showed no biochemical recurrence or metastasis after follow-up of 16-91 months. Conclusions: iIDC-P is a special type of intraductal carcinoma of the prostate and differs from intraductal carcinoma within high-grade prostate cancer. iIDC-P has unique molecular characteristics and may represent as a molecularly unique in situ tumor of prostate cancer.

Cytologic features of differentiated high-grade thyroid carcinoma: A multi-institutional study of 40 cases.

Differentiated high-grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high-grade features while retaining the architectural and/or cytologic features of well-differentiated follicular-cell-derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management. The pathology archives of six institutions were searched for cases diagnosed on resection as "high-grade thyroid carcinoma" using WHO criteria. The fine-needle aspiration (FNA) cohort represents a 10-year period (2013-2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features. Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI-RADS score of 4 or 5 (95.2%). Three main high-grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p<.05); 68% of DHGTC cases were associated with high-risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E. Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high-grade thyroid carcinoma. Other findings include high-risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.

Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA).We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays.The cohort was comprised of 8 females and males, each, with an age range of 33–79 years (median, 59), and a tumor size range of 3.4–15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally.Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC.MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Comprehensive Clinical-Pathologic Assessment of Malignant Phyllodes Tumors: Proposing Refined Diagnostic Criteria.

The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present: permeative borders, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses per 10 high-power fields (HPF), and stromal overgrowth. We assessed the performance of this recommendation to capture MPTs and features predictive of distant metastasis in a multi-institutional retrospective study. Of 65 MPTs, most cases had at least focally permeative borders (58, 89%), with marked stromal cellularity in 40 (61.5%), marked atypia in 38 (58.5%), ≥10 mitoses per 10 HPF in 50 (77%), and stromal overgrowth in 56 (86%). Distant metastases were observed in 20 (31%) patients (median follow-up 24.5mo, 1 to 204). Only 13 of 65 (20%) cases had all 5 morphologic features, while only 7 of 20 (35%) cases with distant metastases had all 5 features. In univariate analysis, only marked stromal atypia ( P =0.004) and cellularity ( P =0.017) were associated with decreased distant metastasis-free survival. In multivariate Cox regression, the combination of stromal overgrowth, marked stromal cellularity, and atypia (C-index 0.721, 95% CI: 0.578, 0.863) was associated with decreased distant metastasis-free survival. The current World Health Organization recommendation will miss a significant number of MPTs with distant metastases. We propose refined diagnostic criteria for MPTs: (1) stromal overgrowth combined with ≥1 feature(s) (marked cellularity, marked atypia, or ≥10 mitoses per 10 HPF), or (2) in the absence of stromal overgrowth, marked cellularity combined with ≥1 feature(s) (permeative borders, marked atypia, or ≥10 mitoses per 10 HPF).

Primary epithelioid hemangioendotheliomas and angiosarcomas of the pleura: a clinicopathological and immunohistochemical analysis of 13 cases

Thirteen cases of primary epithelioid hemangioendotheliomas (EHE) and epithelioid angiosarcomas (EA) of the pleura are presented. The patients were 7 men and 6 women between the ages of 34 and 65 years (mean: 47 years). The patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Diagnostic imaging revealed the presence of either diffuse pleural thickening or pleural nodules involving the serosal surfaces. Open surgical biopsies were obtained in all cases. Histologically, eight tumors were characterized by the presence of a cellular proliferation composed of medium-sized epithelioid cells embedded in a myxohyaline stroma and a variable spindle cell component. Cellular atypia was mild to moderate and mitotic activity ranged from 1 to 2 per 2mm2. Immunohistochemical stains for vascular markers, including CAMTA1 were positive, confirming a diagnosis of EHE. Five cases of epithelioid angiosarcomas were characterized by a neoplastic cellular proliferation admixed with areas of necrosis and hemorrhage and characterized by medium-sized epithelioid to spindle-shaped cells with eosinophilic cytoplasm, round to oval nuclei and prominent nucleoli. In addition, marked cytologic atypia and a mitotic activity ranging from 3 to 5 per 2mm2 were identified. Immunohistochemical studies demonstrated positive staining for vascular markers; however, CAMTA1 was negative. Clinical follow-up obtained in eleven cases showed that all patients had died within 30 months post diagnosis. The current study highlights that even though it may be important to histologically separate EHE from EA for academic purposes, primary pleural origin of these tumors appears to portent an aggressive clinical behavior.

Atypical metanephric adenoma: Shares similar histopathological features and molecular changes of metanephric adenoma and epithelial-predominant Wilms' tumor.

BackgroundMetanephric adenomas (MAs) are rare, benign renal tumors. Wilms’ tumors (WTs) are malignant embryonic tumors that originated from nephrogenic blastemal cells. However, some tumors have similar morphology to both MA and epithelial-predominant WT, which makes differential diagnosis difficult. We aimed to analyze the morphological, immunophenotypic and molecular changes in overlapping cases to explore their attribution.Methods and resultsTwenty MAs, ten WTs, and nine cases with MA/WT overlapping histological features were studied. Twenty tumors demonstrated the typical morphological spectrum of MA with high cellularity and were composed of tightly packed small, uniform, round acini with a lower Ki67 index. Almost all MAs (94.7%, 18/19) were detected with BRAF V600E mutation. The ten WTs were epithelial-predominant WTs with glands, rosettes and glomerular structures, which also showed a higher Ki-67 index (up to 60%), invasive growth patterns, and a lack of BRAF mutation. However, the other nine overlapping cases showed two components: typical MA-like areas and epithelial WT-like areas. The cells of the WT-like areas were tubular, columnar and showed marked cytological atypia, with a Ki-67 proliferative index of up to 30%. The immunophenotype of these overlapping lesions was not significantly different from that of typical MA and they positively expressed WT1 and CD57. The BRAF V600E mutation was detected in both WT-like and MA-like areas in nine overlapping tumors. The follow-up data of 31 patients were analyzed, with a median follow-up time of 66 months (range, 8-45 months). Even though most patients with WT underwent radiotherapy or chemotherapy after surgery, two died, and one had liver metastasis. No MA or overlapping cases showed any evidence of recurrence or metastasis after surgery.ConclusionsThe molecular changes in tumors with overlapping morphological features were the same as those of typical MA; thus, we think that these tumors should be classified as MA and further called atypical MA. It is important to note that atypical MA is not a neglected subtype of MA. It possesses different histological morphology and a higher Ki-67 index but has the common imaging characteristics, immunophenotype and gene expression as typical MA, and patients usually have a good prognosis.

Primary Salivary Gland Neoplasms (Malignant) Epithelial Myoepthial Carcinoma: A Case Report

Epithelial myoepthial carcinoma (EMEC) is rare, low grad tumor with epithelial and myoepithelial components and frequent local recurrence, also called glycogen rich adenoma (clear cell pattern), myoepithelioma (spindle and plamocytiod patterns), myoepithelial carcinoma (if only myoepithelial differentiation and marked cytologic atypia). Occurs most frequently in the major salivary glands and accounts for approximately 1% of all salivary gland neoplasms that usually occurs in parotid gland but can be occur in variety of sites such as the nasal cavity, paranasal sinus and base of the tong. In fact, due to the rarity of the epithelial myoepithelial carcinoma,there is no uniformity of data in the literature band vary different therapeutic strategies have been suggested.

64-Year-Old Woman With Aphasia and Troponin Elevation

64-Year-Old Woman With Aphasia and Troponin Elevation

TERT promoter mutation in a paediatric Spitzoid melanoma – A case report

Optimal classification of skin tumours with Spitz morphology assists patient prognosis and therapy. Deciding between atypical Spitz tumour and Spitzoid melanoma often requires molecular testing. We report a Spitzoid lesion arising on a 12-year-old female’s knee. Microscopic features of marked cytologic atypia, lack of maturation, deep mitotic figures, and loss of p16 expression led to a provisional diagnosis of atypical Spitz tumour and prompted further molecular workup. Alongside copy number abnormalities of the CCND1, MYB and RREB1 genes, the homozygous deletion of CDKN2A and a TERT promoter (TERT-p) hotspot variant were identified.

Papillary Urothelial Carcinoma

A 70-year-old man with a history of hypertension and asymptomatic atrial flutter presented with pyuria on urine microscopic examination. Cystoscopy revealed bladder lesions emanating from the left ureteral orifice and posterior lateral wall (Figure, A and B). Upper tract evaluation with ureteropyelograms revealed no other lesions. Transurethral resection of the bladder tumors was performed to further characterize these lesions. Histopathological examination revealed the presence of noninvasive high-grade urothelial carcinoma (Figure, C and D). Specifically, these grossly exophytic lesions correspond to papillary structures with well-defined fibrovascular cores that are lined by urothelial cells with loss of cell polarity and marked cytologic atypia. Tumor grade, presence of tumor invasion, tumor size, recurrence, and multifocality are some factors that predict the risk of disease progression.1Babjuk M. Böhle A. Burger M. et al.EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016.Eur Urol. 2017; 71: 447-461Abstract Full Text Full Text PDF PubMed Scopus (1253) Google Scholar In this patient, the presence of high-grade lesion would stratify him as having a high risk of progression.2Soukup V. Čapoun O. Cohen D. et al.Prognostic performance and reproducibility of the 1973 and 2004/2016 World Health Organization grading classification systems in non-muscle-invasive bladder cancer: a European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.Eur Urol. 2017; 72: 801-813PubMed Google Scholar Patients with high-risk disease are typically managed with transurethral resection of the bladder tumor coupled with intravesical therapy.1Babjuk M. Böhle A. Burger M. et al.EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016.Eur Urol. 2017; 71: 447-461Abstract Full Text Full Text PDF PubMed Scopus (1253) Google Scholar,3Hall M.C. Chang S.S. Dalbagni G. et al.Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update.J Urol. 2007; 178: 2314-2330Crossref PubMed Scopus (633) Google Scholar This is typically followed by surveillance to monitor for disease recurrence or progression.

Choriocarcinoma Presenting as a Metastatic Pancreatic Mass: a Cytopathologic Diagnostic Challenge

Abstract Introduction/Objective Choriocarcinoma is a malignant tumor of trophoblasts, with gestational choriocarcinoma as the most common type. It commonly presents with vaginal bleeding and uterine mass; occasionally, hemorrhage due to metastatic disease to the lung, liver, brain, and gastrointestinal tract may be the first presentation. We describe an unusual case of metastatic gestational choriocarcinoma presenting as a pancreatic head mass mimicking a pancreatic neuroendocrine tumor (PanNET). The concern for choriocarcinoma was raised by fine-needle aspiration (FNA) cytology. Methods/Case Report A 32-year-old woman, 16 months status-post caesarian delivery of healthy twins, presented with progressive right upper quadrant and epigastric pain, nausea, and marked elevation of Beta-hCG, lipase, ALT, and AST levels. Abdominal CT revealed a hypoenhancing 2.6 cm pancreatic head mass and multiple liver nodules, suggestive of PanNET with liver metastasis. Endoscopic ultrasound and FNA of the pancreatic mass revealed a poorly differentiated tumor composed of bizarre large malignant cells with marked cytologic atypia, focal spindle cell change, and rare multinucleated cells. By immunohistochemistry, the tumor cells were positive for pancytokeratin, CAM5.2, and CD56 (focally), while negative for synaptophysin, chromogranin, inhibin, P63 and P40. While pancreatic adenocarcinoma and PanNET couldn’t be completely ruled out, metastatic choriocarcinoma was also considered; however, inconclusive immunostaining warranted a tissue biopsy. Follow-up liver biopsy and FNA showed that tumor cells were positive for Beta-hCG and negative for SALL4, placenta lactogen, HepPar1, and TTF1 immunostains, compatible with choriocarcinoma. Molecular analysis using short tandem repeat supported a gestational origin of the tumor. The patient underwent chemotherapy with marked improvement in her status and beta-hCG levels. Results (if a Case Study enter NA) NA Conclusion Although highly aggressive, gestational choriocarcinomas show good treatment response, necessitating accurate diagnosis in cases of an atypical presentation. Choriocarcinoma presenting as metastatic pancreatic mass is extremely rare and poses a diagnostic cytopathologic and radiologic challenge that requires comprehensive correlation with clinical and laboratory data.

Histopathologic spectrum of glomangioma: A clinico-pathologic review

Abstract Introduction/Objective Glomus tumors are mesenchymal neoplasms with glomus body type modified smooth muscle cell differentiation. Most glomus tumors have a benign clinical course. However, rarely, they display malignant histologic features. Methods/Case Report We undertook a retrospective study using a natural language search in CoPath to find surgical pathology cases from 1993-2020 containing “glomus” in the pathology diagnosis. All relevant cases were included, and clinicopathologic data were reviewed in detail. Results (if a Case Study enter NA) A total of 66 tumors were identified, of which 42 were in female (63.6%) and 24 in male (36.4%) patients. The age at surgery ranged from 22 to 79 years with a median of 47.5. Females were significantly younger than males at presentation (p=0.025) by 8.8±3.8 years. Forty cases (60.6%) were located on the digits, 24 in nonvisceral soft tissue of extremities, trunk, and lip (36.4%), and one each in stomach and breast parenchyma. Sixty-three (95.5%) were benign (of which one recurred locally), 2 (3%) were malignant, and 1 (1.5%) was atypical. Four (6%) were multicentric. One case showed mixed histology (oncocytic and classic features) and one was classified as glomangiomatosis. The malignant cases each presented with a single tumor in lower extremity soft tissue in female patients (aged 33 and 49 years). The tumors measured 0.5 and 1.8 cm respectively and showed marked cytologic atypia in both and increased mitotic activity in the first. They were both completely excised. Conclusion The majority of glomus tumors are benign, however 3% are malignant. The most common location is the digits, followed by soft tissue. This tumor is more commonly seen in female patients. Unusual histologic variants such as glomangiomatosis and oncocytic component at times may create some difficulty to reach the diagnosis, especially on small biopsies. Unusual locations such as stomach can lead to a wrong diagnosis such as carcinoid, especially in a small biopsy material.

The Difficulty of Post-Operative Surveillance of Calcitonin Negative Medullary Thyroid Cancer

Background: As a differentiated thyroid tumor, medullary thyroid cancer (MTC) typically maintains the secretory function of the c-cells with resultant increase in serum calcitonin level along with frequent elevations in serum chromogranin A (CgA) and carcinoembryonic antigen (CEA). Clinical Presentation: A 71-year-old female with history of multinodular goiter underwent a thyroid nodule biopsy after routine ultrasound surveillance revealed enlargement of two right lower lobe nodules compared with prior imaging. Fine needle aspiration (FNA) of one 3.1 x 1.9 x 2.7 cm right thyroid nodule revealed cellular material composed of spindle-shaped neoplastic cells, some of them with marked cytologic atypia, suspicious for a neuroendocrine tumor, specifically medullary thyroid carcinoma. A PET/CT scan was performed after injection of Gallium-68 dotatate radiotracer and revealed intense focal radiotracer activity in the approximately 2.5 x 2.1 cm right thyroid mid lower pole heterogeneous hypodense mass with tiny calcification inferiorly, consistent with the patient’s known tumor. There was no evidence of cervical octreotate avid metastatic lymphadenopathy and a chest x-ray showed no evidence of active pulmonary disease. The patient subsequently underwent a right partial thyroidectomy with isthmusectomy. Histopathology revealed a 2.8 x 1.9 x 1.9 cm neoplasm composed of spindle and polygonal cells growing in solid nests with neuroendocrine-type nuclei. Immunostains showed the tumor to be positive for AE1-AE3 cytokeratins, chromogranin, synaptophysin and CEA. It was focally positive for TTF-1 and calcitonin. Thyroglobulin and PAX-8 were negative. Using the AJCC 8th edition staging system, the tumor was staged a pT2Nx with margins uninvolved by carcinoma and no extrathyroidal extension or lymphatic invasion. Angioinvasion was present. Additional serum studies included a normal calcitonin value of <2.0 pg/ml (reference range 0-5.1 pg/ml), CEA 2.6 ng/ml (reference range <6.0 ng/ml), and a mildly elevated chromagranin A at 133 ng/ml (reference range 0-95 ng/ml). Plasma metanephrines, normetanephrines, vasoactive peptide, and glucagon levels were all unremarkable. Our patient’s surgical recovery was normal and two months later she remained asymptomatic without evidence of recurrence or metastasis. Discussion: The diagnosis and post-operative surveillance of medullary thyroid cancer is challenging; even more complicated is the rare case of calcitonin-negative MTC. The cause of calcitonin-negative MTC remains unclear. Further studies are needed for the discovery and development of novel biomarkers for post-operative surveillance and evaluation of clinical relapse.

Clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus

Objective: To investigate the clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus. Methods: Fifty-two cases of basal cell layer type high-grade squamous dysplasia of the esophagus were collected at PLA Joint Logistics Support Force 989 Hospital (34 cases) and Beijing Chaoyang Hospital (18 cases) from 2009 to 2019. The clinical, histological and immunohistochemical features were characterized. Related literature was also reviewed. Results: The median age of the 52 patients was 64 years (range 43-72 years). There were 35 men and 17 women, with a male to female ratio of 2.1∶1.0. There were 8 cases in the upper esophagus, 41 in the middle esophagus and 3 in the lower esophagus. According to the Paris Classification, 24 cases were 0-Ⅱb and 28 cases were 0-Ⅱc. Endoscopic examination showed that the color of the lesions was red and the edge was irregular. The narrow band imaging showed that the lesions were brown, and the microvascular abnormalities on the mucosal surface were observed with high magnification. Iodine staining of the lesions showed no or light staining and irregular border. Histologically, the basal layer of squamous epithelium was hypercellular, with large and hyperchromatic nuclei, and disordered cell arrangement. A high proportion of the cases showed a down-growth pattern and associated invasive squamous cell carcinoma. The immunohistochemical staining of 37 cases showed that the mutation rate of p53 was 48.6% (18/37), the median of Ki-67 labeling index was 60% (range 20%-90%), the median of Ki-67 labeling index of the basal tumor cells was 26/HPF (range 5-70/HPF), and the rate of abnormal Ki-67 distribution pattern was 37(100.0%). According to the initial pathological diagnosis, there were 8 cases of low-grade intraepithelial neoplasia, 2 cases of atypical epithelial cells and 42 cases of high-grade intraepithelial neoplasia. Conclusions: The basal cell layer type high-grade squamous dysplasia of the esophagus has a unique morphology. The dysplasia is mainly limited to the lower half part of the squamous epithelium. With marked cytological atypia and prominent invasiveness pattern, it is likely to develop into invasive squamous cell carcinoma at an early stage of the disease. The rate of pathologic misdiagnosis (such as low-grade lesion) is high. The p53 mutation and Ki-67 abnormal distribution pattern are helpful features for confirming the diagnosis of such high-grade dysplasia.

Papillary Squamous Cell Carcinoma of the Cervix: Human Papillomavirus (HPV) Status and Clinicopathologic Features

Abstract Introduction/Objective Papillary squamous cell carcinoma (PSCC) is a rare cervical neoplasm composed of papillae lined by atypical squamous/transitional cells without koilocytosis. It is unclear whether PSCC is related to human papillomavirus (HPV) infection, though rare cases were reportedly associated with HPV type 16. PSCC is thought to be more common in postmenopausal women. Some authors have suggested that PSCC may be understaged due to the prominent exophytic nature of the superficial aspect and relatively deep location of underlying infiltrative nests. It has also been suggested that PSCC has a tendency to recur and/or metastasize late. Methods The surgical pathology database of a single large academic institution was searched for squamous cell carcinoma (or squamous cell carcinoma in situ) with papillary features from the cervix, sampled between 1996 and 2018. PCR for human papillomavirus (HPV) L1 protein was run, with sequencing of positive samples. Results 5 cases diagnosed as “papillary squamous cell carcinoma” were identified. Patient age ranged from 21–63 years (mean 46 years). All tumors showed papillary architecture, often with complex branching and/or fusion. The neoplastic cells had a squamous/transitional appearance with moderate to marked cytologic atypia and at most focal keratinization. Stage ranged from pT1b1 to pT3b (clinical stage IB1 to IVB). HPV L1 PCR was positive in only one case; sequencing confirmed HPV type 16. Upon closer review, the HPV-positive case was from the youngest patient and showed adjacent low-grade squamous intraepithelial lesion (LSIL) as well as focal koilocytic change within the papillary tumor. Conclusion Our findings suggest that even in patients with HPV infection, PSCC may be an HPV-independent malignancy. In multiple cases, it was difficult to obtain definitive histologic evidence of invasion prior to resection.

High-Grade Serous Carcinoma of the Fallopian Tube

A woman presented with pelvic pain, increased abdominal girth, and gastrointestinal symptoms. A pelvic adnexal mass was identified by imaging and resected. Pathology diagnosed the mass as high-grade serous carcinoma (HGSC) of the fallopian tube.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Which gene is most commonly altered in high-grade serous carcinoma?a.KRASb.BRAFc.NRASd.TP53 Answer: d. TP53 Some form of TP53 gene alteration is found in nearly all HGSCs.1Kurman R.J. Shih I. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory.Am J Surg Pathol. 2010; 34: 433-443Crossref PubMed Scopus (1196) Google Scholar,2Kurman R.J. Carcangiu M.L. Herrington C.S. Young R.H. WHO Classification of Tumours of Female Reproductive Organs. IARC, Lyon, France2014Google Scholar In contrast, KRAS and BRAF mutations are more frequent in low-grade serous carcinoma (LGSC).1Kurman R.J. Shih I. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory.Am J Surg Pathol. 2010; 34: 433-443Crossref PubMed Scopus (1196) Google Scholar,2Kurman R.J. Carcangiu M.L. Herrington C.S. Young R.H. WHO Classification of Tumours of Female Reproductive Organs. IARC, Lyon, France2014Google Scholar Further, a significant percentage of HGSCs arise from intraepithelial carcinoma of the fallopian tube whereas LGSC commonly evolves from a continuum of ovarian neoplastic precursors including serous borderline tumor. Morphologically, HGSC often has an infiltrative mixture of papillae, glandular, and solid structures composed of cells with marked cytologic atypia, and frequent mitotic activity. LGSC also has destructive invasion, but the micropapillae have low-grade nuclear features and a lower frequency of mitotic activity.

Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases

BackgroundPhyllodes tumours (PTs) are rare fibroepithelial tumours accounting for <1% of all breast tumours. We assessed clinicopathological features and their prognostic effect in a single-institution patients’ cohort.MethodsPatients diagnosed with PT between 2001 and 2018 at our institution were identified. Clinical, surgical and pathological features were collected. Phyllodes-related relapse was defined as locoregional or distant recurrence (contralateral excluded), whichever first.ResultsA total of 166 patients were included: 115 with benign, 30 with borderline and 21 with malignant PTs. Features associated with malignant PT were younger age, larger T size, higher mitotic count, marked cytological atypia, stromal overgrowth, stromal hypercellularity, necrosis and heterologous differentiation (all p<0.01). The majority of patients with malignant PT underwent mastectomy (63.2% vs 3% of benign/borderline, p<0.001) and had negative surgical margins (83.3%). 4-year cumulative phyllodes-related relapse incidence was 7% for benign/borderline PT and 21.3% for malignant PT (p=0.107). In the entire cohort, marked cellular atypia and heterologous differentiation were associated with worse phyllodes-related relapse-free survival (HR 14.10, p=0.036 for marked vs mild atypia; HR 4.21, p=0.031 for heterologous differentiation present vs absent). For patients with benign PT, larger tumour size was associated with worse phyllodes-related relapse-free survival (HR 9.67, p=0.013 for T>5 cm vs T≤2 cm). Higher tumour-infiltrating lymphocytes (TILs) were associated with borderline and malignant PT (p=0.023); TILs were not associated with phyllodes-related relapse-free survival (HR 0.58, p=0.361 for TILs>2% vs≤2%). Overall, four patients died because of PT: three patients with malignant and one with borderline PT.ConclusionsPatients with malignant PT had increased rates of phyllodes-related relapse and phyllodes-related death. Cellular atypia and heterologous differentiation were poor prognostic factors in the entire cohort; large tumour size was associated with an increased risk of phyllodes-related relapse in benign PT.