Cytologic Atypia Research Articles

Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

Vascular Neoplasms With NFATC1/C2 Gene Alterations : Expanding the Clinicopathologic and Molecular Characteristics of a Distinct Entity.

Despite significant advances in their molecular pathogenesis, skeletal vascular tumors remain diagnostically challenging due to their aggressive radiologic appearance and significant morphologic overlap. Within the epithelioid category and at the benign end of the spectrum, recurrent FOS/FOSB fusions have defined most epithelioid hemangiomas, distinguishing them from epithelioid hemangioendothelioma and angiosarcoma. More recently, the presence of EWSR1/FUS :: NFATC1/2 fusions emerged as the genetic hallmark of a novel group of unusual vascular proliferations, often displaying epithelioid morphology, with alternating vasoformative and solid growth, variable atypia, reminiscent of composite hemangioendothelioma. In this study, we further our understanding and morphologic spectrum of NFATC -fusion positive vascular neoplasms by describing 9 new cases, including soft tissue locations and novel fusion partners. Combining with the initial cohort of 5 cases, a total of 14 patients were analyzed, showing slight female predilection and an age range of 10 to 66 (mean 42y). Twelve patients had solitary lesions, while 2 had multifocal polyostotic (pelvic bones) disease. Overall, 12 lesions were intra-osseous and 2 in soft tissue. By targeted RNA Fusion panels or FISH, there were 6 cases of EWSR1::NFATC1 , 4 EWSR1::NFATC2 , 2 FUS::NFATC2 , 1 EWSR1 rearrangement, and 1 with a novel FABP4::NFATC2 fusion. Follow-up was available in 4 patients. One patient experienced 2 local recurrences, 11 and 15 years postdiagnosis, and one patient experienced progressive disease despite multimodality treatment (curettings, embolization, radiation) over 3 years. In summary, our extended investigation confirms that NFATC -related fusions define a distinct group of vascular neoplasms with variable architecture, epithelioid phenotype, and cytologic atypia, commonly located in the bone, occasionally multifocal and with potential for local recurrence and aggressive behavior but no metastatic potential. Molecular analysis is recommended in diagnostically challenging cases with atypical histology to exclude malignancy.

Clinical and histopathological features of lentigo maligna and lentigo maligna melanoma: a retrospective analysis in Korea.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are rare in Asian countries. The histopathological diagnosis of LM is often challenging, and misdiagnosis is common. Although histopathologic features of LM/LMM are known, statistical analysis of them were scarcely reported. In this study, we aimed to investigate the histopathological characteristics of LM/LMM in Korean patients and identify key histopathological clues distinguishing LM from benign lentigo. We performed a retrospective study of the clinical and histopathological features of patients diagnosed with LM/LMM at our center between 2011 and 2022. We assessed the histopathological features in each case based on 16 pathological criteria according to previous literature. Pathologically confirmed cases of benign lentigo were analyzed for comparison. Twenty-one patients (10 with LM and 11 with LMM) were analyzed. Several statistically significant difference existed between the features of LM and benign lentigo (N = 10), including asymmetry of overall structure (p < 0.001), cytologic atypia (p < 0.001), predominant single-cell proliferation (p < 0.001), melanocytic nests (p = 0.033), melanocytes forming rows (p = 0.003), pagetoid spread of melanocytes (p < 0.001), and hair follicle invasion by atypical melanocytes (p < 0.001). Degree of solar elastosis was more severe in group "Age ≥ 60" (p = 0.015), and group "Diameter ≥ 20 mm" (p = 0.043). Presence of elongated rete ridges were less common in the older than 60 age group (p = 0.015) and group "Diameter ≥ 20 mm." Invasion was associated with mitosis (p = 0.001, OR 49.285), multinucleated cells (p = 0.035, OR 17.769), and degree of lymphocyte infiltration (p = 0.004). This study investigated the clinical and histopathologic characteristics of LM and LMM in Koreans. Although histopathological diagnosis is challenging, especially in the early stages of LM, our data showed essential histopathological changes in architectural, cytological, and dermal patterns. Considering the potential aggressiveness of LM/LMM, it is essential to recognize its histopathological features and provide timely management.

Unclassified Sex Cord/Gonadal Stromal Testis Tumour with a “Pure “Spindle Cell Component: Pathological Features And Review of The Literature

Background: About 2-5% of adult testicular tumors are classified as sex cord/stromal tumors, which are an uncommon group of tumors of the testis. Occasionally, a small percentage of Sex Cord/stromal Testis Tumors (SCST) that are primarily composed of spindle cells seem to be unclassifiable. There are about six cases reported where spindle cells predominate, four of which are consisting purely of spindle cells. At the morphologic level, a striking resemblance to a fibroma has raised the notion of a possible fibrothecoma, but this is not supported by the immunohistochemistry, and the features are consistent with an unclassified sex cord/stromal tumor with a “pure” spindle cell component. Description: A 45-year-old man with a firm mass in the lower pole of the left testis for 3 years. The patient had no comorbidities and no features of endocrinopathies. All blood tests were normal. The ultrasound showed a solitary hypoechoic mass with increased blood flow by Doppler scan. A well-circumscribed tumor measuring 30mmx 15mm with no discernible capsule was identified macroscopically. Microscopy showed a well-circumscribed spindle cell lesion with no necrosis, cytological atypia, or mitoses. The tumor cells appeared spindled with eosinophilic cytoplasm, vesicular nuclei, and occasional nucleoli. No nuclear grooves were noted in the tumour cells. No vascular invasion was present. Actin, calretinin, CD99, S100, and inhibin were positively immunoreactive. Conclusion: The findings were consistent with an Unclassified pure spindle SCST, a rare tumor with a benign course that must be distinguished from several spindle cell neoplasms. There are no biochemical markers for the diagnosis of this tumor, thus requiring meticulous clinical examination, especially if it is small in size. We report a case of “pure spindle cell sex cord stromal tumour of the testis in a 45 years old man in which the histomorphological as well as the immunohistochemical features are consistent with the diagnosis of unclassified sex cord/stromal testis tumor with “pure” spindle cell component.

Sarcomas With RAD51B Fusions Are Associated With a Heterogeneous Phenotype

RAD51B-rearranged sarcomas are rare neoplasms that exhibit a heterogeneous morphology. To date, 6 cases have been reported, all involving the uterus, including 4 perivascular epithelioid cell tumors (PEComas) and 2 leiomyosarcomas (LMS). In this study, we describe the morphologic, immunohistochemical, and molecular features of 8 additional sarcomas with RAD51B rearrangement, including the first extrauterine example. All patients were women with a median age of 57 years at presentation. Seven tumors originated in the uterus, and one in the lower extremity soft tissue, with a median tumor size of 12 cm. Histologically, 4 tumors showed predominantly spindle cell morphology with eosinophilic fibrillary cytoplasm, with or without nuclear pleomorphism, whereas 2 tumors exhibited pleomorphic epithelioid cells, featuring clear to eosinophilic, granular cytoplasm. Two neoplasms exhibited undifferentiated cytomorphology, including one with uniform small blue round cells. All tumors showed high-grade cytologic atypia and high mitotic activity (median: 30/10 high-power fields), whereas coagulative necrosis was noted in 6 cases and lymphovascular invasion in 2. By immunohistochemistry, 2 showed myoid and melanocytic markers in keeping with PEComa, whereas 4 cases were only positive for smooth muscle markers consistent with LMS (including 3 myxoid). The remaining 2 cases had a nonspecific immunoprofile. Five cases tested by targeted RNA sequencing (Archer FusionPlex, Illumina TruSight) showed different fusion partners (HMGA2, PDDC1, and CEP170). RAD51B rearrangements were identified by FISH in the remaining 3 cases. Targeted DNA sequencing in 2 cases was negative for TSC gene alterations. Clinical outcome, available in 5 patients (median follow-up, 19 months), revealed 3 local recurrences, 2 lung metastases, and 4 deaths due to disease. Our results expand the spectrum of sarcomas with RAD51B fusions, demonstrating variable clinical presentations, morphologic spectrum, and fusion partners. These tumors have a predilection for a uterine location, with either LMS, PEComa, or undifferentiated phenotypes, and are associated with an aggressive clinical course.

Clinical study of benign endometrial hyperplasia and response of Unani drugs with estimation of serum oestrogen levels

Endometrial Hyperplasia represents a spectrum of irregular morphological alterations, made by abnormal proliferation of the endometrial glands results in an increase in gland to stroma ratio. When compared to endometrium from proliferation phase of the cycle. The proliferation glands in endometrial hyperplasia can vary greatly in size and shape, and cytological atypia may be present. According to Hakeem Ajmal Khan in his book HAZIQ, Hakeem Anwer Ali Khan in his book Taleem-ul Qabela and Hakeem Shafaqat Azmi in his book Amraaz –e- Niswaan said that the Endometrial hyperplasia is caused due to alteration of humors and the temperament of uterus and the increase in retaining power (quwat-e- masika) of uterus is the cause of thickening of inner layer of uterus which leads to warm-e- daroon-e- raham. Objective: To prove the efficacy of Unani medicine in Benign Endometrial Hyperplasia Methodology: The study was carried out in the P.G Department of Qabalath – O – Amraaz – E – Niswaan at Government Nizamia Tibbi College and Hospital, Charminar, Hyderabad. Randomized single blind study with Pre and Post-test evaluation was conducted. Total 40 cases of Endometrial Hyperplasia were selected which is divided into two Groups. Group A – 20 Cases and Group B – 20 Cases. Inclusion Criteria: Age 25Yrs. to 55 Yrs., Only married women, Simple Hyperplasia with cystic without atypia, Complex hyperplasia with adenomatous without atypia, History of irregular menstrual cycles, PCOD’s, Hormone replacement therapy (HRT). Exclusion Criteria: Simple Hyperplasia with cystic Atypia, Complex Hyperplasia with Adenomatous Atypia/Carcinoma in Situ, Uterine Fibroids, Uterine Polyps, PID (Pelvic Inflammatory Disease), Systemic Disorders like tuberculosis, heart Diseases, Renal Disorders &amp; Neurological Disorder, Unmarried Women. Drugs which were selected for trial were finalized on the basis of these following properties like Mohalil – e- Aoram, Qhabiz, Musaffi – E – Khoon &amp; Dafae Tafoon were selected for the study. In group A &amp; B drugs given in the form of Joshanda, Sufoof, Humool and Zimaad. Group A- JOSHANDA: Gul – e – Banafsha, Babuna, Tukhm – e – Kataan, Sumbul e Tib, Gul – e – Tisu, Makoh – e – Khuskh, Arjun Chall, Gul – e – Surkh. HUMOOL: Mazo, Gul – e – Surkh, Shib – e – Yamani, Chub Zard, Zulal – e- Tukhme Bartang. SUFOOF: Musli Safaid, Mushtagi, Mochras, Gul – e – Surkh, Maye Kalan. ZIMAAD: Gul- e – Banafsha, Makoh – e – khuskh, Magaz – e – Fuloos – e- Qayashambar, Kashneez – e- Sabz, Tukhme Alsi. Group B – JOSHANDA: Gul – e – Banafsha, Babuna, Tukhm – e – Kataan, Sumbul e Tib, Gul – e – Tisu, Makoh – e – Khuskh, Arjun Chall, Gul – e – Surkh. HUMOOL: Luab – e – Tukhme Alsi, Luab –e- Tukhme Khatmi, Aab – e – Kashneez Sabz, Gul – e- Surkh, Makoh – e – Khushk. SUFOOF: Gul – e – Dhava, Gul- e- Gaozaban, Gul – e- Surkh, Gul – e – Banafsha. ZIMAAD: Gul – e – Tisu, Gul – e – Banafsha, Raswat, Tukhme Alsi, Magz – e – Gheegawar. Results: Group A 8 patients (40%) cured; 7 patients (35%) Partially relieved. Whereas in Group B 11 patients (55%) cured and 7 patients (35%) Partially relieved. Conclusion: The study proved efficacy of Unani formulation with good results in Benign Endometrial Hyperplasia with no major side effects.

Recurrent Melanoma Inguinal Lymph Node as unknown Primary Disease: A Case Report

A-63-year old male presented with left inguinal swelling. Swelling was non-tender and firm in consistency. It measured 5×3×1 cm. Fine needle aspiration cytology was done. Smears were stained by H&amp;E and Papanicolaou staining methods. Smears were hypercellular and showed plasmacytoid cells. Nucleomegaly and anisonucleosis were seen. Clumped chromatin with single conspicuous nucleolus was also seen. The patient had a recurrent lesion and cytological atypia. Cytological findings suggested the tumour to be a malignant melanoma. Keywords: Malignant tumour, Groin swelling, Cytoplasmic melanin pigment granules.

Challenges in Diagnosis of Steatohepatitic Hepatocellular Carcinoma on a Biopsy Specimen

Abstract Introduction/Objective Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Steatohepatitic hepatocellular carcinoma (SH-HCC) is a subtype that is associated with metabolic syndrome and alcoholic hepatitis. Diagnosing SH-HCC can be extremely challenging on a biopsy specimen, given that steatohepatitis-like changes can be seen in focal nodular hyperplasia and hepatic adenoma. Herein, we present a very challenging case of SH-HCC that was initially diagnosed as a well-differentiated lesion after multi-institutional consultations. Methods/Case Report A 54-year-old female with past medical history of diabetes and hypertension presented with flank pain and a 2.7 cm liver mass in a background of diffuse hepatic steatosis by CT scan, concerning for malignancy. Viral hepatitis serology workup was negative. Results (if a Case Study enter NA) The liver core biopsy reveals a well-differentiated hepatic lesion with areas of steatosis, fibrosis, and features of steatohepatitic changes including ballooning hepatocytes and Mallory-Denk bodies. No significant cytological atypia is identified. No definitive loss of reticulin is seen by reticulin stain. The cytological or architectural atypia was insufficient in isolation to diagnose HCC. The lesion cells are positive for HepPar-1 and Arginase-1, while negative for Glypican. Diffuse sinusoidal CD34 staining is present. Ki-67 proliferative index is approximately 2%. These changes did not permit a confident diagnosis of hepatic adenoma or hepatocellular carcinoma. The case was sent for consultation by multiple institutions with a consensus diagnosis of well-differentiated hepatic lesion/neoplasm. A follow-up liver wedge resection shows a hepatic neoplasm with areas of loss of reticulin staining. Focal stromal invasion is present. The neoplastic cells are positive for HepPar-1, Arginase-1, glutamine synthetase and Glypican (patchy). Final diagnose was rendered as SH-HCC. Conclusion The diagnosis of SH-HCC requires high level of suspicion on a biopsy specimen, especially in a background of steatohepatitis. A reticulin stain and immunohistochemical stains may not be helpful. Clinical- radiological correlation should always be considered.

Pleomorphic Adenoma With Cystic Change, Extensive Squamous Metaplasia and Positive Block-Like p16 Staining Pattern: A Sheep In Wolf’s Clothing

Abstract Introduction/Objective Pleomorphic adenoma, the most common benign salivary gland neoplasm may show squamous metaplasia in up to 25% of cases, and less frequent cystic change. We report an unusual case of pleomorphic adenoma with cystic change, extensive squamous metaplasia and block-like p16 staining that was misdiagnosed as metastatic p16-positive squamous cell carcinoma in a limited core biopsy. Methods/Case Report A 78-year-old female with no history of malignancy presented with a right neck painless mass. PET-CT demonstrated a hypermetabolic ovoid mass adjacent to the right submandibular gland measuring 1.7 cm concerning for metastatic disease within a lymph node. Fine needle aspiration of lesion was hypocellular and showed cystic contents and rare atypical squamoid cells. Core biopsy of the lesion demonstrated sheets of squamoid cells with mild to moderate cytologic atypia in a hyalinized fibrotic stroma. Immunostain for p16 showed cytoplasmic and nuclear block-staining pattern. The biopsy was diagnosed as metastatic p16-positive squamous cell carcinoma. Subsequent human papilloma virus (HPV) in situ hybridization for low- and high-risk types was negative. The patient underwent right level 1B neck dissection revealing a pleomorphic adenoma arising at the periphery of the submandibular gland with cystic change and extensive central squamous metaplasia. Repeated p16 staining showed diffuse positivity in the area with squamous metaplasia and heterogenous staining in the non-metaplastic areas. Cobas HPV-PCR test covering 14 high-risk HPV subtypes was also negative. Results (if a Case Study enter NA) NA Conclusion We describe the unusual coexistence of extensive squamous metaplasia, cystic change and aberrant p16 staining pattern in an exophytic pleomorphic adenoma to raise awareness of how these changes individually, and more so in combination can mimic squamous cell carcinoma. The mechanism of p16 overexpression in metaplastic PAs appears to be independent of HPV infection.

Inflammatory pseudotumor of frontal sinus mimicking an aggressive malignancy: a rare case with diagnostic challenge on fine needle aspiration

Abstract Introduction/Objective Inflammatory pseudotumor (IPT) of sinonasal tract is a rare disease that sometimes mimicks malignancy in radiographic findings. Diagnosis of IPT on fine needle aspiration (FNA) is challenging due to limited cellularity and lack of architectural evaluation. Methods/Case Report Patient is a 59-year-old female presented with left front head swelling, facial pain and pressure. Imaging demonstrated a 3.0 cm hypermetabolic frontal sinus mass with osseous erosion through the calvaria table and deviating the adjacent dura, suspicious for malignancy. Also, an incidental 6.8 cm renal mass was identified and was proven to be clear cell renal cell carcinoma. FNA from frontal sinus showed loosely cohesive atypical cells with prominent nucleoli and occasional mitotic activity mixed with lymphoplasmacytic inflammation and eosinophils. Extensive immunostains showed that the lesional cells were only weakly stained for CD10 and desmin. Because of prominent cytologic atypia and radiological concerning for malignancy, FNA was diagnosed as malignancy not further classified. The patient underwent frontal sinus resection and the surgical specimen showed spindle cell proliferation surrounded by reactive woven bone with plump osteoblasts in a myxocollagenous stroma containing mixed lymphoplasmacytic cells and eosinophils. The spindle cells are positive for actin and calponin, negative for ALK. The spindle cells and plump osteoblasts corresponded to the atypical cells observed on FNA. The overall finding is consistent with IPT, although inflammatory myofibroblastic tumor cannot be completely ruled out. During follow up, the patient developed metastatic renal cell carcinoma in lung. Her frontal sinus lesion was stable for 17 months after surgery. Results (if a Case Study enter NA) NA Conclusion IPT of sinonasal tract is a rare lesion that sometimes demonstrate aggressive radiologic features. FNA from IPT poses a diagnostic challenge and can be misinterpreted as malignancy due to prominent cytologic atypia. Being aware of this rare entity helps avoid misdiagnosis and triggers the request for core biopsy during onsite evaluation.

Endometrial stromal tumor presenting as multiple endometrial polyps with limited infiltration; a novel presentation

Abstract Introduction/Objective The 2020 WHO classifies endometrial stromal tumors into endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma, and undifferentiated sarcoma. Minimal irregularity of the interface is allowed in ESN (up to 3 foci of &amp;lt;3 mm). In a small number of cases, the irregular interface exceeds the acceptable criteria for ESN but relatively limited compared to most LGESS. These cases are classified as endometrial stromal tumor with limited infiltration. These tumors may recur, and it is best managed as LGESS. Methods/Case Report We report a case of endometrial stromal tumor in a 42-year-old female who presented with abnormal vaginal bleeding. Imaging showed multiple fibroids. She underwent total abdominal hysterectomy and bilateral salpingectomy. On gross examination three endometrial polyps with sharp demarcation from the adjacent myometrium were identified (largest 4 cm). Histology revealed proliferation of uniform small cells with scant cytoplasm and round to oval nuclei with rare mitotic figures in a delicate network of arterioles. Immunostains showed positive staining for CD10 and estrogen receptor while negative for Caldesmon. These polyps were mainly confined to the endometrium with only small foci of irregular border with the myometrium. No vascular invasion, high grade cytologic atypia or necrosis were seen. The tumor showed JAZF1-SUZ12 gene fusion. This case was diagnosed as an endometrial stromal tumor with limited infiltration. Results (if a Case Study enter NA) NA Conclusion In conclusion, endometrial stromal tumors are commonly submucosal or intramural, we report a rare case that presented as multiple endometrial polyps, with very limited myometrium infiltration. To our knowledge, no cases have been reported so far. It is essential to be cognizant of this entity when dealing with polypoid lesions of the endometrium, they may recur and should be managed as LGESS.

INTRAOPERATIVE FROZEN SECTION ANALYSIS OF ENDOMETRIOID OVARIAN BORDERLINE TUMOR: A DIFFICULT DIAGNOSIS

Abstract Introduction/Objective Borderline ovarian tumors (BOT) comprise approximately 15% of all primary ovarian neoplasms; of these endometroid borderline ovarian tumors (EBOT) are much rarer (2-3%). BOT is often potentially misdiagnosed as a malignant tumor based on its challenging histomorphological features and thus, treated aggressively. Herein, we present an unusual case of EBOT with adenofibromatous pattern in a 50-year-old gravida 3, para 2 female diagnosed on intraoperative frozen sections (IOFS). Methods/Case Report Patient with history of endometriosis presented with left lower quadrant abdominal pain. MRI revealed complex bilateral ovarian masses with solid and cystic components measuring 5 cm and 6.7 cm in right and left ovary, respectively. An ovarian malignancy was suspected. Patient underwent exploratory laparotomy, total abdominal hysterectomy with bilateral salpingo-opherectomy, and omentectomy. Grossly, bilateral ovaries (BO) showed intact capsule with solid and cystic components. On IOFS, the solid areas demonstrated endometrioid glands arranged in a lobular fashion with squamous morules. The cystic component demonstrated papillary projections with squamous differentiation. Cytology is mildly atypical at best. Based on these findings, a diagnosis of EBOT was made, necessitating staging. Differential diagnoses include atypical endometriosis, endometrioid adenofibroma (EAF) and endometrioid adenocarcinoma (EA). Lack of endometrial stroma surrounding the glands ruled out endometriosis. Presence of CC with papillary architecture ruled out EAF and lack of destructive stromal invasion with desmoplasia, confluence of glands and significant cytologic atypia ruled out EA. Final histopathological diagnosis of formalin-fixed paraffin-embedded specimen revealed EBOT, pT1bN0M0. Uterus and cervix revealed endometrial hyperplasia with atypia, adenomyosis, leiomyomas, and endocervical polyp. Results (if a Case Study enter NA) NA Conclusion The accurate diagnosis of BOT during IOFS is critical as it directs surgeons towards staging studies and in choosing conservative surgical treatment over aggressive treatment especially in cases of young women who desire future childbearing. As this is a rare entity, it serves the pathologist well to keep all relevant differential diagnoses in mind.

Mycosis Fungoides and Granulomatous Slack Skin: A Single Entity With Distinct Clinical Phenotypes.

Granulomatous cutaneous T-cell lymphoma includes mycosis fungoides with significant granulomatous inflammation (GMF) and granulomatous slack skin (GSS), listed in the WHO classification as a subtype of mycosis fungoides (MFs).1 These overlapping entities have shared clinical and histopathologic features which can present a diagnostic challenge. The dominance of the granulomatous infiltrate and the often sparse lymphocytic infiltrate frequently with minimal cytological atypia are features that distract from the correct diagnosis, even when raised by the clinician. We describe the clinical and histopathologic characteristics of 3 cases of granulomatous cutaneous T-cell lymphoma, illustrate the close clinical and pathologic relationship between GMF and GSS and emphasize the diagnostic difficulties that the granulomatous infiltrate can present. Furthermore, we demonstrate, for the first time, considerable elastolysis in a significant proportion of classical (Alibert-Bazin) MF lesions and therefore postulate that the differences observed between GMF and GSS are one of degree and secondary to their anatomic location rather than reflecting meaningful separate entities.

Tissue Eosinophilia in B-cell Lymphoma: An Underrecognized Phenomenon.

Tissue eosinophilia is seldom reported in B-cell lymphoma. It poses diagnostic challenges and frequently leads to the consideration of other diagnoses, particularly T-cell lymphomas. The scarce literature underscores the need for in-depth studies to enhance awareness and understanding of this phenomenon. We investigated 54 cases of B-cell lymphoma with notable tissue eosinophils, analyzing clinical information, hematoxylin and eosin staining, immunohistochemistry, and PCR-based clonality analysis. Nodal marginal zone lymphoma (NMZL) emerged as the most prevalent type (n=26), followed by B-cell lymphoma, not otherwise specified (n=13), diffuse large B-cell lymphoma (n=10), follicular lymphoma (n=2), chronic lymphocytic leukemia/small lymphocytic lymphoma (n=1), extranodal marginal zone lymphoma (n=1), and primary cutaneous marginal zone lymphoma (n=1). Shared features across different lymphoma types, best exemplified by NMZL, included plasmacytic differentiation (57.7%), increased vascularity (84.6%) with a tendency for perivascular distribution of neoplastic cells, and a tumor microenvironment abundant in T cells and histiocytes; some cases showed increased PD-1-positive cells. These features often raise consideration of angioimmunoblastic T-cell lymphoma. Along with clonality analysis, features supporting the diagnosis of B-cell lymphoma included cytological atypia in B cells rather than T cells, and the lack of follicular dendritic cell meshwork expansion. In addition, diffuse large B-cell lymphoma frequently exhibited interfollicular distribution and monocytoid appearance, indicating the possibility of transformed NMZL. Collectively, tissue eosinophilia can occur in diverse B-cell lymphomas but is most prevalent in tumors with a postgerminal stage of differentiation.

Pathological features of primary cardiac myxoid tumour in dogs: a review of 11 cases (2002–2022)

This report documents the pathological features of primary cardiac myxoid tumour (MT) in 11 dogs. Macroscopically, all the tumours were located in the tricuspid valve (TV), its septal leaflet being predominantly affected. Therefore, it appears that the TV is the most common site of occurrence for cardiac MT in dogs. Two gross anatomical types of canine valvular MT were evident. Seven of the 11 tumours were round or oval with a smooth or gently lobulated and glistening surface, while the other four were gelatinous, multilobulated and polypoid, with an irregular surface. Microscopically, in nine cases the tumours had an abundant myxoid matrix within which elongated spindle-shaped cells with no remarkable cytological atypia were sparsely embedded, suggesting a benign character (ie, myxoma). In the other two cases the tumours consisted of variably dense, haphazardly arranged, interlacing streams of anaplastic spindle-shaped or polygonal cells containing many mitotic figures, indicative of a malignant form of myxoma (ie, myxosarcoma). Isolated or clustered collections of myxoma cells (eg, cords, rings, syncytia) characteristic of human atrial myxoma were only rarely evident or lacking in all 11 cases, indicating that rarity or absence of such structural features may be specific to valvular MTs. Immunohistochemical findings were indicative of smooth muscle differentiation of the neoplastic cells. Tumour embolization to the intrapulmonary arteries and/or tumour implantation on the endocardium of the right heart chambers was evident only in the four cases of irregular-surfaced MT.

Risk Profile of High-grade Cervical Lesions and Cervical Cancer Considering the Combination of Cytology, HPV Genotype, and Age among Women Undergoing Colposcopy.

The present study aims to establish a risk profile for high-grade cervical lesions and cervical cancer (CIN2 + ) in women undergoing colposcopy at the Hospital do Câncer de Barretos, through the analysis of Human Papillomavirus (HPV) infection, cervical cytology, and patient's age. Retrospective cross-sectional study based on a computerized database of women aged ≥ 18 years old who underwent colposcopy at the Prevention Department of the Hospital do Câncer de Barretos from 2017 to 2019. A total of 3,411 women were included, 58.0% were positive for high-risk-HPV test, with a higher prevalence of CIN2+ for HPV16 (30.3%) and other HPV (45.0%). Cytological findings that suggest invasive cervical cancer (squamous cells or adenocarcinoma), regardless of the status of HPV test, showed 100% diagnosis of CIN2 + , while atypias that suggest high-grade lesions, HSIL and ASC-H, positive for HPV test, showed in 86 and 55.2%, respectively, diagnosis of CIN2 + . ASC-H cytological results among women aged > 40 years old and negative HPV were mainly associated with benign findings. We observed that ≤ CIN1 has a higher prevalence among older women with negative HPV, while for high-grade lesions there is an increase among young women HPV16- and/or 18-positive. In cancer diagnosis, we observed a predominance of HPV 16/18 regardless of the age group. The highest risks of precursor lesions and cervical cancer were found among women with positive HPV 16/18 tests and severe cytological atypia in population screening tests. In addition, cytological findings of ASC-H HPV negative in women > 40 years old usually represent benign findings in histological investigation.

Integrated genotype–phenotype analysis of familial adenomatous polyposis-associated hepatocellular adenomas

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by numerous colorectal adenomas. In addition, FAP patients may develop extraintestinal manifestations. Several cases of hepatocellular adenomas (HCA) detected accidentally in FAP patients have raised the so-far unsolved question of whether they represent a specific manifestation of FAP or a mere coincidence. To investigate the incidence of liver tumors in FAP patients, we analyzed our diagnostic database from 1991 to 2021. Among the 58 hepatic mass lesions identified, five HCAs occurring in three patients with FAP were identified, and comprehensive morphological, immunohistological, and molecular analysis employing targeted next-generation sequencing was conducted for characterization. The HCAs in this study showed no cytological or histological atypia. They displayed a diffuse, strong positivity for glutamine synthetase but no nuclear beta-catenin immunostaining. In two patients, the adenomas showed moderate immunoreactivity against serum amyloid A. Consistent with the diagnosis of FAP, molecular profiling revealed a pathogenic germline mutation of the APC gene in all analyzed adenomas as well as deleterious somatic second hits. All somatic mutations were localized between codons 1345 and 1577. No mutations were found in the catenin beta 1 gene. HCA in FAP patients can be a specific, although rare, neoplastic manifestation of this inborn disease and represents a distinct subgroup of HCAs. These benign tumors represent an important differential diagnosis for hepatic metastases in FAP patients and require adequate clinical and molecular (diagnostic) assessments for optimal patient guidance.

Case report: Ghost cell odontogenic carcinoma in a dog: diagnostics and surgical outcome.

A 6 year-old spayed female Poodle presented with a mandibular mass. Radiographic examination revealed osteolysis from the right mandibular canine to the fourth premolar, along with horizontal bone loss and dorsal displacement of the right mandibular first and second premolars. Skull cone beam computed tomography revealed osteolysis at the level of the right mandibular canine and fourth premolar. A destructive bone lesion was observed in the apical area of the right mandibular canine, with mass invasion of the interradicular bone of the right mandibular first molar near the mandibular canal. Consequently, unilateral total mandibulectomy and skin flap surgery were performed. Histopathological examination revealed poorly demarcated and infiltrative neoplastic epithelial cells that formed small islands and trabeculae. Neoplastic cells exhibited the malignant features of cytological atypia and high mitotic activity. Furthermore, the neoplastic epithelial cells frequently showed ghost cell changes and were diagnosed as ghost cell odontogenic carcinoma (GCOC). The dog was followed up for 1 year, during which no severe complications or local recurrence was observed, except for slight mandibular drift, tongue protrusion, and drooling. This case report describes the clinical features, diagnostic imaging, and histologic features of an unreported GCOC in a dog and the favorable outcome following surgical resection.

Lymphoglandular Complex-Like Colorectal Carcinoma-A Series of 20 Colorectal Cases, Including Newly Reported Features of Malignant Behavior.

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features, including lesion size, endoscopic appearance, location, procedure, follow-up, AJCC stage, and mismatch repair status. We recorded the presence of the following histologic features: haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, presence of lymphovascular invasion and perineural invasion, presence of lamina propria, cytologic atypia as low- or high-grade, presence of goblet cells in the invasive component, and the presence of a surface lesion. Most cases (9 of 13) were described endoscopically as sessile polyps with an average size of 1.56 cm. Most cases (90%) were associated with a surface lesion, of which the majority were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (3 of 18). All cases of LGCC demonstrated haphazard gland distribution and either gland angulation, fusion, or solid nest formation. A portion of cases demonstrated single-cell infiltration (35%) and desmoplasia (50%), and rarely lymphovascular invasion was present (5%). A subset (10%) of cases invaded beyond the submucosa. Deficient mismatch repair was present in 22% (2 of 9) of cases for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38% (3 of 8). No cases demonstrated disease recurrence or disease-specific mortality. Overall, LGCC represents an enigmatic subset of carcinomas that is important to distinguish from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.

Clinicopathological comparison and assessment of Ki67, p53 and c-myc immunoexpression in carcinoma cuniculatum, verrucous carcinoma and microinvasive squamous cell carcinoma of the oral cavity

ObjectiveTo illustrate the clinicopathological comparison of carcinoma cuniculatum (CC), verrucous carcinoma (VC) and microinvasive squamous cell carcinoma (MISCC) and to compare the immunoexpression Ki67, p53 & c-myc in these entites. Material and methodsClinical and histopathological parameters observed in total 67 cases (12 cases of CC, 22 cases of VC and 27 cases of MISCC). Ki67 & p53 labelling index and c-myc immunoexpression (localization of stain (1: cytoplasmic; 2: nuclear; 3: both), intensity of stain (1: mild; 2: moderate; 3: strong) and distribution of stain in epithelium (1: basal third; 2: up to middle third; 3: up to upper third; 4: invasive islands)). ResultsCC predominantly showed keratin filled crypts, keratin microabscess, microsequestra formation and lymphocytic exocytosis. VC showed broad pushing invasive front, parakeratin plugging along with verrucous projections. Irregular infiltrating rete ridge pattern and severe cytological atypia were findings of MISCC. Ki67 LI was 12.70 % in CC, 23.34 % in VC and 28.27 % in MISCC. p53 LI was 44.167 % in CC, 30.18 % in VC and 29.51 % in MISCC. Ki67 LI showed statistically significance difference between CC and MISCC. Moderate to strong cytoplasmic immunoexpression was found in epithelium as well as in invasive islands of MISCC compared to CC and VC. ConclusionCC shows endophytic epithelium proliferation with mild to moderate dysplasia and no definite invasive front in contrast to VC. High p53 in CC basal cells correlate with more endophytic epithelial proliferation. Significant high Ki67 LI in invasive islands of MISCC supports its aggressive nature. p53, Ki67 and c-myc panel may be helpful as an adjunct in difficult cases with poorly oriented specimens.