Moderate Nuclear Atypia Research Articles

Early Genetic Divergence of High-grade Carcinomas Originating from Low-grade Ovarian Serous Neoplasms

The current paradigm implicates a fallopian tube precursor as the origin of most ovarian high-grade serous carcinomas (HGSCs). However, a rare subset of HGSCs develop via a distinct pathway from low-grade serous ovarian neoplasms (namely, serous borderline tumors and low-grade serous carcinoma). This alternate pathway for the development of HGSC and other poorly differentiated carcinomas of the ovary is not well understood. To elucidate the molecular pathogenesis and evolutionary trajectory of histologic transformation of low-grade serous neoplasms, we performed whole exome sequencing on microdissected low-grade and higher-grade components from 7 cases of serous borderline tumor or low-grade serous carcinoma associated with a synchronous or metachronous indeterminate/high-grade carcinoma. In most cases, there were relatively few somatic mutations shared between matched low-grade and higher-grade tumors compared with private mutations specific to each component (ie, phylogenetic trees with short trunks and long branches). Truncal mutations, present across all tumor samples from a given patient, included known drivers of low-grade serous neoplasms: KRAS (G12D, n = 4), BRAF (G469A, n = 1), NF2 (n = 1), and USP9X (n = 1). Transformation to HGSC was associated with a TP53 mutation with bi-allelic inactivation in 3 cases, all with severe nuclear atypia, and associated with genome-wide copy number alterations and allelic imbalances. TP53-wildtype tumors comprised a morphologic spectrum, which included indeterminate-grade serous carcinomas with moderate nuclear atypia and high mitotic activity, although lacking extensive chromosomal instability (n = 2) and poorly differentiated carcinomas (n = 2, including a high-grade Mullerian carcinoma and an undifferentiated carcinoma with sarcomatoid features). In summary, synchronous and metachronous low-grade serous neoplasms and higher-grade carcinomas are clonally related. Early genetic divergence, most evident in cases with TP53 mutations, suggests that high-grade transformation may be a relatively early molecular event.

Warthin-like Variant of Mucoepidermoid Carcinoma of the Parotid Gland

A 57-year-old woman with a 2-year history of a left infra-auricular mass with no associated symptoms presented with a 6.0 cm ´ 4.0 cm ´ 3.0 cm firm, non-tender, movable mass. No imaging was done. Fine needle aspiration biopsy (FNAB) revealed sheets of epithelial cells that had abundant dense grayish-blue cytoplasm in a mucinous background with abundant lymphocytes (Figure 1), suggestive of salivary gland neoplasm with oncocytic or oncocytoid features (Category IVB, Salivary Gland Neoplasm of Uncertain Malignant Potential).1 Total parotidectomy revealed a 4.3 X 3.2 X 3.0 cm deep lobe lesion with a tan-grey to dark brown, smooth and dull external surface. Cut sections showed a cream-white to pink, lobulated, heterogenous cut surfaces. Microscopically, the lesion was unencapsulated with poorly demarcated borders. The neoplastic cells were arranged in haphazard sheets and surrounded by abundant lymphocytes. The tumor cells had abundant eosinophilic and granular cytoplasm compatible with oncocytes with mild to moderate nuclear atypia. There were occasional cystic spaces that contained mucin though mucocytes were not readily apparent. (Figure 2) Necrosis, perineural and lymphovascular space invasion or anaplasia were not evident.

Analysis of the clinicopathological features of tailgut cyst with emphasis on the development of neoplastic lesions.

Tailgut cyst is a rare congenital cyst occurring in the retrorectal space and development of neoplastic lesions in tailgut cyst has been reported. Due to the rarity of the tumor, the histogenesis of neoplastic lesions in tailgut cyst has remained elusive. In the present study, the clinicopathological features of tailgut cyst were analyzed with a particular focus on the development of neoplastic lesions. The clinicopathological features of four patients with tailgut cyst (one female and three males) were retrospectively reviewed. No symptoms were present in two patients. Perineal discomfort, and constipation and urinary retention, were described in the other two patients, respectively. Magnetic resonance imaging showed that the cystic lesions were hypointense on T1- and hyperintense on T2-weigted images in all patients. Histopathological analysis revealed that all lesions were multilocular, and cystic walls were covered by squamous and ciliated epithelia without nuclear atypia. The development of neoplastic lesions was noted in two patients. Dysplastic change composed of piling-up proliferation of glandular cells with mild to moderate nuclear atypia was present in one patient, and invasive adenocarcinoma with a dysplasia component was observed in another patient. Dysplasia of the glandular cells, as seen in two patients in the present series, may be a precursor lesion of invasive adenocarcinoma; therefore, adenocarcinoma arsing in tailgut cyst may show a dysplasia-carcinoma sequence. While the reported incidence of neoplastic lesions in tailgut cysts is ~9% or less, their frequency remains to be accurately determined. Therefore, complete surgical resection is important for the management of patients with tailgut cyst. Additional clinicopathological and molecular studies with large cohorts may be required to clarify the histogenesis of neoplastic lesion in tailgut cyst.

Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6-rearranged tumours resembling NF with atypical features have been reported. One index case of LGMS of the deltoid in a 56-year-old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break-apart probe identified two additional cases. These cases were investigated with RNA-sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low-quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast-like multinucleated giant cells, and peripheral lymphoid aggregates. Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

Cytomorphological Profile of Graves' Disease and its Co-relation with anti-TPO Antibody

Objective: Thyroid diseases are major health problems in our society, which are manifested by alteration in hormone secretion, enlargement of the thyroid gland. FNAC plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost and with a diagnostic accuracy rate of 92%. This study was designed to cytomorphological profile of Graves’ disease and its co relation with anti TPO antibody. Materials and Methods: This is a prospective analytical study of fifty patients with clinically enlarged thyroid gland presenting at STG Hospital, Haldwani, Nainital during Oct 2019 to Oct 2022. FNAC smears of these patients were studied and correlated with cytomorphological findings of different types, grades of thyroiditis and hormone level of T4, T3 and T.S.H. Results: Females were mostly affected by thyroid diseases than males. Female patients were 39 (78%) and male patients were 11 (22%). In the present study, patients were in the age group of 13 to 74 years of age. High T3 levels were noted in 80% high T4 levels were found in 90%. Low TSH level was found in only 64%, normal TSH level found in 34% and 2% presented with high TSH level. 34 patients (68%) found high anti-thyroid peroxidase antibody titre >34 U/ml. Cytomorphology revealed moderate to high cellularity in 88% cases, mild to moderate nuclear atypia in 86% and presence of marginal vacuoles in 82%. Lymphocytic infiltrate found in 24% cases and epithelioid cell granuloma in 14% cases. Conclusion: Thyroid cytology proves to be a reliable, simple, and cost-effective first-line diagnostic procedure with high patient acceptance and with rare, usually easily treated and not life-threatening complications. We recommend further studies with a larger population to validate our study. Keywords: Thyroiditis, Graves' Disease, Malignancy Goiter, Histopathology

A Case of Myxoid Pleomorphic Liposarcoma with Rhabdoid Cells: A Diagnostic Pitfall.

Myxoid pleomorphic liposarcoma (MPLS) is an extremely rare tumor listed in the fifth edition of the WHO classification (2020). Histologically, it mainly comprises a mixture of myxoid and pleomorphic liposarcoma-like components. Genetically, it lacks FUS/EWSR1::DDIT3 fusion and MDM2 amplification. Herein, we describe an example of MPLS with rhabdoid cells in a 10-year-old girl who presented with a growing mass in the right inguinal region. The specimen from the wide excision measured 68 mm × 55 mm × 43 mm, and a circumscribed and lobulated mass was observed in the subcutaneous tissue. Histologically, oval-to-short, spindle-shaped, proliferating tumor cells with moderate nuclear atypia and mesh-like capillaries against a myxoid background were noted. Adipocytes were observed focally, while rhabdoid cells were observed multifocally. Immunohistochemically, the tumor showed inconsistent reactivity for desmin but was negative for MYOD1, myogenin, MDM2, and CDK4. Fluorescence in situ hybridization revealed no DDIT3 rearrangement. Despite adjuvant chemotherapy, the tumor metastasized to the thoracic cavity 24 months after excision. The metastatic lesions contained abundant lipoblasts rather than rhabdoid cells, and we concluded this tumor was a MPLS. The presence of rhabdoid cells could be a diagnostic pitfall, and recognizing such a variation in histology would help improve diagnostic accuracy.

Fibrosarcoma Presenting as Marjolin Ulcer – A Rare Case Report

Marjolin ulcer is a rare malignancy that arises in previously traumatised or chronically inflamed skin, particularly after burns, with an average latency period of 36 years. Nearly 75-90% marjolin ulcers are diagnosed as squamous cell carcinoma but other neoplasms like basal cell carcinoma, melanoma, fibrosarcoma etc have also been rarely reported. In this case, a 52-year-old male presented with a painless bleeding mass over lower chest wall rapidly increasing in size from last 2 years. He had suffered burn at the same site 20 years ago. Biopsy was reported as spindle cell neoplasm. Wide local excision revealed a poorly circumscribed subcutaneous spindle cell neoplasm exhibiting variable cellularity, fascicular to storiform architecture, mild to moderate nuclear atypia and scattered gaping thin-walled blood vessels. The neoplastic cells showed diffuse strong staining with CD34 in the less cellular area and patchy positivity in the cellular more mitotically active areas. The tumor cells were immunonegative for EMA, p63, SMA, CD99 and STAT6. The final diagnosis rendered was Dermatofibrosarcoma Protuberans dedifferentiating in to fibrosarcoma. Although sarcoma presenting as a Marjolin ulcer is exceedingly rare, it should be kept in mind in differential diagnosis of spindle cell malignancy arising at a burn site.

Clear-Cell Mesothelioma of Uterine Corpus: Diagnostic Challenges in Intraoperative Frozen Sections

The clear-cell variant of epithelioid mesothelioma is an extremely rare neoplasm of the peritoneum. It shares histomorphologic features overlapping with a wide variety of tumors including carcinomas and other non-epithelial neoplasms. The diagnosis of peritoneal clear-cell mesothelioma is not always straightforward, despite known immunohistochemistry (IHC) markers. Due to its rarity, this entity may be diagnostically confused with other clear-cell neoplasms, particularly in intraoperative frozen sections. Here, we present a case of clear-cell mesothelioma originating in the uterine serosa that was initially misdiagnosed as clear-cell adenocarcinoma in the intraoperative frozen section. Microscopically, the tumor showed diffuse tubulocystic spaces of variable size lined by clear cells with moderate nuclear atypia. Immunohistochemical staining confirmed the diagnosis of clear-cell mesothelioma. Recognition of this entity, albeit rare, is important as the diagnosis may significantly affect the management considerations. The judicious use of an IHC panel helps to distinguish this tumor from other mimickers.

A retrospective study of canine oral extramedullary plasmacytoma over a 15-year period (July 2004-July 2019): Treatment, histologic parameters and clinical outcomes.

A total of 45 cases of canine oral extramedullary plasmacytomas (EMPs) presented to a tertiary referral institution over a 15-year period were examined. Histologic sections of 33 of these cases were examined for histopathologic prognostic indicators. Patients underwent variable treatment including surgical intervention, chemotherapy and/or radiation therapy. Long term survival was observed in the majority of dogs with a median survival time of 973 days (2-4315 days). However, almost 1/3 of dogs had progression of plasma cell disease, including two cases with myeloma-like progression. Histologic characterization of these tumours did not reveal criteria to predict tumour malignancy. However, cases without tumour progression did not exceed 28 mitotic figures in ten 400× fields (2.37 mm2 ). All cases with tumour related death showed at least moderate nuclear atypia. Oral EMPs may represent a local manifestation of systemic plasma cell disease or singular focal neoplasia.

Aggressive Pilomatrixoma of the Scalp in a Geriatric Patient: A Rare Occurrence

Pilomatrixoma is a benign cutaneous adnexal neoplasm that arises from the hair matrix. This lesion is typically observed in the first two decades of life, with most cases occurring before the age of 20. However, it is rare in the elderly. While aggressive and malignant variants of pilomatrixoma exist, they are rarely reported compared to their benign counterparts. In this case, we present an instance of aggressive pilomatrixoma in a 90-year-old female. The patient exhibited a large ulceroproliferative growth on the scalp. A preliminary biopsy was performed, followed by wide local excision. Both the biopsy and excision specimens exhibited characteristics of pilomatrixoma, with a focal infiltrative growth pattern and moderate nuclear atypia. Features indicative of malignancy, such as geographic necrosis, brisk mitosis, atypical mitosis, vascular invasion, and perineural invasion, were not observed. Therefore, the diagnosis of aggressive pilomatrixoma was made. Wide local excision and subsequent skin grafting were conducted, with no involvement of deeper subcutaneous tissue and intact pericranium. The patient is currently faring well during follow-up. This case underscores the importance of meticulous histopathological examination for distinguishing aggressive variants, as they carry a higher risk of recurrence and aid in distinguishing aggressive pilomatrixoma from carcinoma. Failure to recognise the aggressive variant may result in inadequate management.

A new scoring system for the grading of conventional chondrosarcoma: Its clinicopathological significance.

Chondrosarcoma is the second most common primary malignant bone tumor, which produces cartilaginous matrix without neoplastic osteoid or bone formation. The histological grade in the WHO Classification of Soft Tissue and Bone (2020 edition) is the most important factor in predicting the clinical outcome of conventional chondrosarcoma, but the lack of clarity in its detailed definition is occasionally problematic. Here, we reviewed conventional chondrosarcoma cases and validated the significance of histological findings. Moreover, we proposed a new scoring system of conventional chondrosarcoma. Clinicopathological features of 60 cases of conventional chondrosarcoma and 21 cases of dedifferentiated chondrosarcoma were reviewed. Moderate to severe nuclear atypia was correlated with distant metastasis. Moderate and severe nuclear atypia, high cellularity, and >1 % myxoid change were correlated with adverse overall survival. On the other hand, cases with mild nuclear atypia showed no tumor-related death and no metastases. Based on the above results, we proposed a new scoring system based on nuclear atypia (mild: 0, moderate: +1, severe: +2), cellularity (no and mildly increased cellularity: 0, moderately and diffusely increased cellularity: +1), necrosis [(-): 0, (+): +1], and chondromyxoid area [(-): 0, (+): +1]. Each grade was defined as follows: cases with only mild nuclear atypia as grade 1, cases with total score 1-3 excluding mild nuclear atypia as grade 2, and cases with total score 4 or 5 as grade 3. There were 18 cases (30 %) of grade 1 including 5 cases (28 %) of local recurrence, but no metastasis or tumor-related death; 26 cases (43 %) of grade 2 including 2 cases (8 %) of local recurrence, 3 cases (12 %) of metastasis, and 1 case (4 %) of tumor-related death; and 16 cases (27 %) of grade 3 including 4 cases (25 %) of local recurrence, 6 cases (38 %) of metastasis, and 5 cases (31 %) of tumor-related death. There was no statistically significant association between the histological findings and dedifferentiation. From this study, we propose a new histological scoring system for the grading of conventional chondrosarcoma, based on nuclear atypia, cellularity, necrosis, and myxoid change. Using this system, conventional chondrosarcoma may be clearly classified into three grades: grade 1, non-metastasizing; grade 2, metastasizing but rarely life-threatening; and grade 3, frequently metastasizing and life-threatening.

Sclerosing pneumocytoma: A rare and easy to miss diagnosis on lung biopsy

Sclerosing pneumocytomas (SP) are rare tumours originating from pneumocytes, comprised of two cell types: surface cells and round cells.1 The tumour is heterogeneous and displays four patterns in varying proportions: solid, papillary, sclerotic and angiomatous.1 SP are extremely difficult to diagnose on small samples, such as aspirates and core biopsies,2 and are commonly misdiagnosed as lung adenocarcinoma or carcinoid.3 We present a case of a 60-year-old male who underwent right lower lobe lung nodule core biopsy, which showed a lepidic and acinar growth pattern with surrounding desmoplastic-to-sclerotic stroma and moderate nuclear atypia.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis

Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43–85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8–11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND).

Ovarian Serous Surface Papillary Borderline Tumor: Sea Anemone Sign

HomeRadioGraphicsVol. 41, No. 7 PreviousNext Cases from the Cooky JarFree AccessOvarian Serous Surface Papillary Borderline Tumor: Sea Anemone SignC. Austin Wheeler , Ciléin Kearns, Valery L. Turner, Tushar R. GargC. Austin Wheeler , Ciléin Kearns, Valery L. Turner, Tushar R. GargAuthor AffiliationsFrom the Department of Radiology, University of Alabama at Birmingham School of Medicine, 619 19th Street S, JT N338, Birmingham, AL 35249 (C.A.W.); Medical Research Institute of New Zealand, Wellington, New Zealand, and Artibiotics, Wellington, New Zealand (C.K.); Department of Radiology, Stanford University School of Medicine, Stanford, Calif (V.L.T.); and Department of Radiology, Seth GS Medical College and KEM Hospital, Parel Mumbai, Maharashtra, India (T.R.G.).Address correspondence to C.A.W. (e-mail: [email protected]).C. Austin Wheeler Ciléin KearnsValery L. TurnerTushar R. GargPublished Online:Nov 1 2021https://doi.org/10.1148/rg.2021210201MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In On the pathway from benign cystadenoma to malignant cystadenocarcinoma, borderline tumors represent a crucial entity within the spectrum of ovarian epithelial carcinogenesis. Of this class, serous borderline neoplasms represent the common subclass (65%) (1).One distinct sub-subclass is named serous surface papillary borderline tumor (SSPBT) for its unique (although not wholly exclusive) imaging features (2) (Figs 1–3). Macroscopically, its surface stroma frequently branches into exophytic papillary stalks; hence the name. When these cystic lesions form frondlike excrescences, they mimic the likeness of a sea anemone at MRI (1,2). Histopathologic analysis even recapitulates this architectural pattern with micropapillary tumor cell proliferation.Figure 1. Classically described sea anemone appearance of a borderline serous surface papillary tumor in a 52-year-old woman. (A) Axial postcontrast T1-weighted MR image of the pelvis demonstrates heterogeneous soft-tissue enhancement with multiple enhancing fronds (arrow). (B, C) Axial (B) and sagittal (C) T2-weighted MR images of the pelvis demonstrate a complex T2-hyperintense adnexal tumor with multiple papillary excrescences (arrow).Figure 1.Download as PowerPointOpen in Image Viewer Figure 2. (A, B) Gray-scale (A) and color Doppler (B) transvaginal US images in a 52-year-old woman (same patient as in Fig 1) show that this mass has internal echogenic content with a branching appearance (arrow in A) and internal vascularity (arrowhead in B). (C) Low-power photomicrograph (hematoxylin-eosin stain) used for histologic correlation shows that epithelial ovarian tumor cells grow as papillary structures (P) in a hierarchical fashion (large, medium, and small papillae). Tumor cells composing papillae are of serous type with eosinophilic cytoplasm and mild to moderate nuclear atypia. No mitotic activity is seen in this case. (Fig 2C courtesy of Longwen Chen, MD, PhD.)Figure 2.Download as PowerPointOpen in Image Viewer Figure 3. Medical illustration shows the sea anemone sign, which features papillary fingerlike projections with internal branching. Associated findings may include coarse calcifications, ascites, para-aortic lymphadenopathy, and spread to the peritoneum. (Reprinted, with permission, from Ciléin Kearns, Artibiotics, Copyright © 2021.)Figure 3.Download as PowerPointOpen in Image Viewer Preoperative detection at diagnostic imaging can be informative because less aggressive borderline tumors tend to carry a more favorable prognosis, potentially altering management. Early identification and treatment are vital, as these tumors commonly manifest in younger women of childbearing age who may benefit from fertility-sparing surgery (1).All authors have disclosed no relevant relationships.

Low‐grade osteosarcoma is predominant in gnathic osteosarcomas: A report of seven cases of osteosarcoma of the jaw

ObjectivePrimary osteosarcoma of the jaw bones is very rare, and histological features of gnathic osteosarcoma remain obscure. The purpose of this study was to describe the clinicopathological features of gnathic osteosarcoma.Materials and methodsSeven cases of gnathic osteosarcoma from Japan diagnosed during the period between 2000 and 2016 were examined retrospectively. The histology of the surgical pathology materials was reviewed by two pathologists. Clinical information was obtained from the hospital's information system.ResultsOf the seven cases, two patients had secondary osteosarcomas. As for the five cases of primary osteosarcoma, their ages ranged from 26 to 58 years (mean: 36.2, median: 28). Histologically, three cases were fibrotic tumors composed of spindle‐shaped cells with mild to moderate nuclear atypia and the collagenous stroma accompanied by woven bones or mature lamellar‐like bones. Two cases had cartilage formation. MDM2 and CDK4 expression was observed in two out of three cases on immunostaining. The histopathology of these three cases was regarded as the counterpart of low‐grade osteosarcomas, namely, parosteal osteosarcoma and low‐grade central osteosarcoma, arising in long bones.ConclusionsThe surprisingly high incidence (60%, 3/5 cases) of low‐grade osteosarcoma explains the reason why gnathic osteosarcomas present a more favorable prognosis than osteosarcomas arising in long bones. Furthermore, it provides insight into the tumorigenesis mechanism of low‐grade osteosarcomas arising in the jaw and other sites.

A submandibular nodule revealing a relapsed bladder urothelial carcinoma

A 69-year-old patient treated for infiltrating bladder transitional carcinoma many years ago presented with a submandibular nodule. The last was fortuitously discovered by the patient a month before he presented to consultation. Physical examination showed a firm subcutaneous nodule of 0.5 cm in diameter in the right submandibular region. At this level skin was inflamed/red and swollen. Otherwise physical examination was within normal. The described nodule above was biopsied. Microscopic examination showed infiltration of the dermis by a carcinomatous proliferation (Fig. 1). Tumor cells were arranged in small nests and clusters surrounded by a fibrous stroma. Tumor cells showed moderate nuclear atypia. Immunohistochemical staining showed positivity of tumor cells for Cytokeratin 7 and P63 (Fig. 2). Therefore, taking into consideration patient’s medical history, microscopic and immunohistochemical findings the diagnosis of CM from urothelial carcinoma was retained. The first case of CM from bladder carcinoma was reported in 1909 [3]. Since then many case have been reported [1,2]. According to cases reported in literature so far, the mean interval of time between the setting of bladder cancer and the appearance of CM is of 18 months approximately. Large tumor size and deep infiltration of the bladder wall are predictive factors of CM. However, cases of CM associated with superficial bladder carcinomas were reported [3]. The certain diagnosis is based on microscopic examination [1,3]. Pathologists should be aware of patient’s medical history to facilitate the diagnosis and choosing appropriate immunostains if necessary especially in front of a poorly differentiated carcinoma[3]. Urothelial carcinomas express Cytokeratin 7 and Cytokeratin 20 antibodies [3]. The occurring of CM in case of bladder cancer darken the prognosis [1,2]. Median survival rates are less than 12 months in published cases so far [1,3]. Treatment consists of chemotherapy if the patient could bare it [1]. Total recovery was detected in 70% of cases of CM treated with chemotherapy. Yet, it does not improve global survival rates [3].

Clear cell borderline tumor without fibromatous component: Pathological and literature review and report of two cases.

The aim of the present study was to examine the clinical outcome of ovarian clear cell borderline tumor (CCBT) through pathological review for cases with clear cell carcinoma (CCC) and CCBT between 1984 and 2015 who received surgery at the National Defense Medical College Hospital using 2020 World Health Organization (WHO) criteria. In addition to the definition of CCBT in 2020 WHO criteria, clear cell with atypia of the glandular epithelium without fibromatous component was added to the diagnostic criteria of CCBT. Two cases with CCBT were identified through review in the current study. There were no cases that changed from the initial CCBT diagnosis that were included in the current study. Case 1 was a 43-year-old woman who received total hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy. Pathologically, cysts were lined by cuboidal, hobnail and clear cells with eosinophilic cytoplasm and moderate nuclear atypia without the fibromatous component. These cells were adjacent to atypical endometriosis and non-atypical endometriosis, and the patient was diagnosed with CCBT. She exhibited no evidence of the disease for 37 months following surgery. Case 2 was a 42-year-old woman who received left salpingo-oophorectomy, partial omentectomy and pelvic lymphadenectomy. The tumor exhibited a cyst (80 mm) and nodular component. Pathologically, the tumor cells were lined by hobnail cells with mild atypia and eosinophilic cytoplasm without the fibromatous component. This patient was diagnosed with CCBT and exhibited no evidence of disease for 20 months following surgery. CCBT without fibromatous component is a rare and non-aggressive histological subtype. Additionally, regardless of fibromatous component, CCBT was able to be diagnosed.

Clinicopathological, immunohistochemical and fluorescence in-situ hybridisation features of early subungual melanoma: an analysis of 65 cases.

Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM. Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases. To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.

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 49years (range 21-73years) 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 2.4cm (range 0.8-3.5cm). 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.

Gastric-type endocervical adenocarcinoma and cervical cytology: Experience at a general hospital and review of the literature.

Gastric-type endocervical adenocarcinoma (GAS) is an uncommon type of endocervical adenocarcinoma that is not associated with human papillomavirus infection. This diagnosis is relatively rare and may portend a worse prognosis than usual-type endocervical adenocarcinoma. Subtle morphological features make it an under-recognised diagnostic challenge. Study of the cytological features of individual cases is valuable in order to increase awareness of this entity. The pathology database of our institution was searched for the diagnosis of GAS and all cytological and surgical specimens for each patient were reviewed. The original cytological interpretation was compared to a retrospective central review interpretation. Clinical history and follow-up results were obtained from the electronic medical record. Four cases of GAS were identified. The findings on initial cervical cytology varied, with GAS found in both patients with negative cervical cytology and those with atypical glandular cells. Cytological findings included endocervical cells arranged in three-dimensional clusters and honeycomb sheets with abundant vacuolar cytoplasm, and in two patients, moderate nuclear atypia with irregular nuclear membranes, coarse chromatin, hyperchromatic nuclei, and prominent nucleoli. In one patient, GAS was incidentally discovered via thorough sampling of a cystic lesion in the superior portion of the endocervical canal. GAS is an aggressive human papillomavirus-independent type of endocervical adenocarcinoma with subtle morphological features and, as our study shows, varying clinical presentation. Given the aggressive nature of GAS and the difficulties in initial diagnosis, increased awareness of this entity among pathologists is crucial.