Mitotic Figures Research Articles

Analysis of Tumor Proliferation Markers in Early-Stage Luminal Breast Cancer: A Comprehensive Study Using Mitotic Activity Index, Ki-67, and Phosphohistone H3 Expression.

Introduction and Aim: Routinely used proliferation markers such as mitotic activity index (MAI) and Ki-67 index show limited reproducibility due to high interobserver variability in breast cancer assessment. Phosphohistone H3 (PhH3), a novel proliferation marker, is gaining attention in breast cancer research. This study aimed to evaluate the inter-rater agreement among MAI, Ki-67, and PhH3 expressions in early-stage luminal breast cancer and assess the impact of replacing MAI with PhH3 index on tumor histological grading. Materials and Methods: Three pathologists assessed MAI, Ki-67, and PhH3 expressions in 66 early-stage luminal breast cancer specimens. Mitotic Activity Index was scored based on mitotic figures in an area of 2 mm2 while Ki-67 index utilized a 14% threshold for positively stained nuclei. Phosphohistone H3 expression cutoff was set at 13 positive cells per 2 mm2. The inter-rater agreement for the 3 variables was analyzed using Cohen kappa statistics. Results: Among the 3 parameters, the kappa score of the PhH3 expression reflected very strong agreement between the 3 observers (κ = 0.991, 0.907, and 0.916). Only moderate agreement was noted for MAI (κ = 0.898, 0.562, and 0.592) and substantial agreement for Ki-67 index (κ = 0.869, 0.673, and 0.678). Moreover, replacing MAI with PhH3 index led to upgrade of histological grade in 15% to 16% of patients. Conclusion: Our study demonstrated that PhH3 is a more reproducible proliferation marker than MAI and Ki-67. Incorporation of PhH3-based mitotic index in breast cancer grading might reduce the variation in the assessment of histological grade.

Histopathological diagnosis of pulmonary sclerosing pneumocytoma in needle biopsy specimens

Objective: To investigate the diagnostic features of pulmonary sclerosing pneumocytoma (PSP) in needle biopsy specimens so as to improve the preoperative diagnostic accuracy and to prevent misdiagnoses. Methods: A total of 79 needle biopsy cases confirmed as PSP in surgical resection specimens were collected in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2015 to January 2023. A retrospective analysis was conducted to investigate the clinical, pathological, and immunohistochemical characteristics of PSP. Results: Among the 79 cases, there were 8 males and 71 females, with an age range of 14 to 67 years (median 47 years). Among the 79 needle biopsy cases of PSP, 5 cases were initially misdiagnosed as adenocarcinoma and 1 as carcinoid preoperatively, while the remaining 73 cases were correctly diagnosed. 84.8% (67/79) of the PSP presented with well-defined, homogeneous, solitary solid tumors on chest imaging. Morphologically, 26.6% (21/79) of the PSP mainly showed a single histological component, 67.1% (53/79) contained two histological components, and 6.3% (5/79) contained three histological components. There were no cases containing all four histological components simultaneously. The tumor was composed of cuboidal cells on the surface and round cells in the stroma and lacked significant cytological atypia and mitotic figures. Some cases exhibited variations in histology and cellular morphology, such as glandular spaces (58.2%, 46/79), sclerotic papillae (46.8%, 37/79), hypercellularity (16.5%, 13/79), and cytological atypia (24.1%, 19/79). Immunophenotyping indicated that both tumor cell types expressed TTF1, EMA and β-catenin, while surface cells expressed pan-cytokeratin and Napsin A, and stromal cells expressed vimentin. In some cases, ER and PR were also expressed. Conclusions: When diagnosing PSP in needle biopsy specimens, the key to avoiding misdiagnosis is recognizing the presence of dual-cell populations within the tumor. The useful clues include presence of cellular papillae, mild cellular atypia, morphological diversity, interstitial foam-like cell aggregates, and prominent background hemorrhage and sclerosis. The characteristic immunophenotype and middle-aged female predilection are also helpful for the diagnosis of PSP.

Non-small cell lung carcinoma with co-expression of TTF1 and p40: a clinicopathological analysis of six cases

Objective: To investigate the clinicopathological features, molecular pathology characteristics, and prognosis of non-small cell lung carcinoma (NSCLC) exhibiting co-expression of p40 and thyroid transcription factor1 (TTF1). Methods: Clinical and pathological data of six NSCLC cases with co-expression of p40 and TTF1 diagnosed at the First People's Hospital of Xiaoshan District, Hangzhou, China from January 2016 to December 2023 were collected. Relevant literature was also reviewed. Results: NSCLC with co-expression of p40 and TTF1 commonly occurred in male smokers and had been in stage Ⅲ-Ⅳ when diagnosis. Microscopic examination revealed that the tumor cells were arranged in solid nests and sheets with marked atypia and visible mitotic figures. There was no prominent evidence of keratinization or glandular formation. The tumor cells diffusely co-expressed p40 and TTF1, exhibiting a dual immunophenotype characteristic of both squamous cell carcinoma and adenocarcinoma. Molecular testing of four NSCLC co-expressing p40 and TTF1 revealed the presence of common EGFR mutations, as well as mutations of NRAS (mutation rate of 2.09%), EML4-ALK (mutation rate of 24.77%), and PIK3CA (exon 10 c.1658 G>C p.S553T, mutation rate of 4.32%). All six tumors were poorly differentiated, highly invasive, and associated with poor prognosis. Four of the six patients experienced widespread metastasis and died within 7 to 30 months after the diagnosis or initial treatment. Conclusions: NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

Transformation sarcomateuse de la tumeur royale chez une patiente atteinte de la maladie de Recklinghaussen à Lomé (Togo)

Introduction: malignant tumors including soft tissue sarcomas can occur during neurofibromatosis type 1. We report a case of sarcomatous degeneration of a plexiform neurofibroma with multivisceral metastases in a Togolese patient with neurofibromatosis type 1. Observation: A 33-year-old female patient with neurofribromatosis type 1 presented with an altered general condition, pain and changes in the appearance of the plexiform tumour of her neurofibromatosis, which had been evolving for one month. Physical examination revealed multiple coffee-white spots (greater than 10), with tumours of soft consistency and variable size, scattered over the body. There was also a larger tumour (approx. 9cmx6 cm), located on the inside of the left ankle, fixed, firm and painful to palpation. The abdomen was enlarged and tender, with no tenderness or contracture. Examination of lymph nodes was normal. Anatomopathological examination of the biopsy-exeresis of this tumour revealed a proliferation of clusters of small, rounded, undifferentiated cells with reduced cytoplasm and hyperchromatic nuclei, with clear anisokaryosis and numerous atypical mitotic figures. There were also a few vascular emboli. We therefore concluded that this plexiform neurofibroma was malignant, and the extension work-up revealed pulmonary, pancreatic and adrenal metastases. The patient died 3 weeks after diagnosis in respiratory distress. Conclusion: Malignant degeneration of plexiform neurofibromas is possible in patients with neurofibromatosis type 1. It is therefore important to monitor these patients for early detection in order to limit the risk of metastasis and death.

Extradigital Symplastic Glomus Tumor and Review of the Literature.

Symplastic glomus tumors are a rare subtype of glomus tumor defined by nuclear atypia without additional markers of malignancy such as large size, deep location, or atypical/prevalent mitotic figures. Glomus tumors, including the symplastic subtype, most commonly present in the subungual area with rarer extradigital presentation. To our knowledge, there have been less than 25 cases of symplastic glomus tumors described in the literature. Herein, we present a case of extradigital symplastic glomus tumor with review of the literature.

Controlled release of hydrogel-encapsulated mesenchymal stem cells-conditioned medium promotes functional liver regeneration after hepatectomy in metabolic dysfunction-associated steatotic liver disease

BackgroundGlobally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis.MethodsMale Lewis rats were fed with a methionine and choline–deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV).ResultsThe regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division.ConclusionsMSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx.

Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis

The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms’ performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models’ performance. We found that the annotators’ object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure.

Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM)and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

Unusual presentation of incidental atypical carcinoid tumor masquerading as carcinoid tumorlets arising from diffuse neuroendocrine cell hyperplasia (DIPNECH): A case report

Introduction: Carcinoid tumorlets are usually incidental findings in lung excisions. These neuroendocrine proliferations should be less than 5 mm, and resemble typical carcinoid (TC) lacking necrosis and elevated mitotic activity. We report a case of atypical carcinoid (AC) presenting as multiple tumors all measuring less than 5 mm, mimicking carcinoid tumorlets. Case Report: Our patient underwent a right upper lobectomy for multifocal invasive lepidic adenocarcinoma. Multiple nodules of neuroendocrine cells less than 5 mm in greatest dimension were noted within the lobectomy. Unlike carcinoid tumorlets, these nodules showed &gt;2 mitotic figures per square millimeter and punctate necrosis. The ACs masqueraded as multiple microscopic tumor foci (greater5 mm) resembling “carcinoid tumorlets” in adjacent background lung tissue next to the adenocarcinoma. However, increased mitoses and punctate necrosis were diagnostic of AC. A background of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) was noted, appeared to be a precursor lesion to AC, and demonstrated the DIPNECH’s preneoplastic potential to evolve directly into an AC. Conclusion: The rare possibility of AC in “tumorlet”-appearing multiple micronodules should be considered in presence of elevated mitotic activity and necrosis in background of DIPNECH.

Unexpected Encounters: Ossifying Fibromyxoid Tumor Unveiled During Evaluation for Inguinal Hernia

Abstract Introduction/Objective Soft tissue pathology often presents diagnostic surprises, elucidating the intricate nature of disease processes. In this introduction, we discuss the unexpected discoveries that can arise during clinical evaluations and emphasize the importance of thorough evaluation in soft tissue pathology. Methods/Case Report We present the case of a 40-year-old male who underwent evaluation for a right inguinal hernia, during which an ossifying fibromyxoid tumor (OFMT) was incidentally discovered. Imaging modalities intended for hernia assessment revealed a 4.5 cm mass abutting the hernia site. Surgical exploration, initiated for hernia repair, unveiled the unsuspected coexistence of a direct inguinal hernia and an OFMT. Histopathological analysis of the excised mass revealed a complex OFMT architecture, characterized by a plexiform growth pattern, fibrous to fibromyxoid matrix, and distinct cellular features. The neoplastic cells exhibited bland round to ovoid nuclei, occasional multinucleation, and scattered mitotic figures. Immunohistochemistry demonstrated variable positivity for desmin and focal positivity for S-100 protein, while CD34, keratin AE1/AE3, smooth muscle actin, and p63 were consistently negative. Notably, the tumor exhibited areas of hypercellularity and easily identifiable mitotic figures, consistent with morphologic features of malignancy in OFMT. Results (if a Case Study enter NA) N/A Conclusion This case highlights the intricate interplay between primary clinical concerns and incidental pathological findings, underscoring the necessity for comprehensive evaluation in soft tissue pathology. Understanding the nuanced histological and immunohistochemical characteristics of OFMT is pivotal for accurate diagnosis and optimal patient management. The unexpected discovery of OFMT during evaluation for inguinal hernia emphasizes the importance of thorough assessment and consideration of incidental findings in clinical practice.

Malignant Peripheral Nerve Sheath Tumor of the Pancreas with Molecular Confirmation: A Case Report with Comprehensive Histopathologic and Molecular Characterization

Abstract Introduction/Objective Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas arising from a peripheral nerve or exhibiting nerve sheath differentiation. They are often associated with neurofibromatosis type 1, and most often arise in the trunk, extremities, or head and neck region. In patients without neurofibromatosis type 1, sporadic de novo or radiotherapy-associated MPNSTs can pose a diagnostic challenge. MPNSTs arising from visceral organs are exceedingly rare. Here we report a case of MPNST arising in the pancreas. Methods/Case Report The patient is a 75-year-old female, MUTYH mutation carrier, with prior history of breast and bladder cancers, each treated with respective local excision and radiation therapy. Magnetic resonance imaging (MRI) performed for pancreatic cancer screening showed a 4.7 cm heterogeneous mass in the pancreatic tail suggestive of pancreatic neoplasm. Fine needle aspiration cytology was non-diagnostic. However, due to the radiologic concern for malignancy, the patient proceeded with surgical resection by distal pancreatectomy with splenectomy. Macroscopically, a 6.5 cm, tan-white, partially necrotic mass was identified in the pancreatic tail. Microscopic examination showed a spindle cell neoplasm arranged in a vague fascicular fashion with moderate nuclear pleomorphism, geographic necrosis, and frequent mitotic figures (15 per 10 high power fields). Fifteen lymph nodes were negative for metastasis. The tumor was confined to the pancreas grossly and microscopically. Immunohistochemical stains showed the neoplastic spindle cells to be positive for TLE1 (diffuse) and S100 (patchy), while negative for SOX10, CD117, DOG1, desmin, actin, MyoD1, ERG, STAT6, and ALK1. In addition, H3K27me3 showed loss of nuclear expression. Next generation sequencing (NGS) revealed gene mutations in NF1, TP53, PIK3CA, and PTEN, and copy number losses involving CDKN2A and CDKN2B. Genome-wide DNA methylation analysis was performed which revealed copy number losses of CDKN2A/B and gains of PTCH1 and MDM2. However, the Sarcoma DNA Methylation Classifier did not provide any diagnostic matches. Overall, the morphologic features, loss of H3K27me3 expression, presence of NF1 and TP53 mutations, and copy number losses in CDKN2A/B supported a diagnosis of high-grade MPNST. The patient has been followed clinically without adjuvant therapy. Results (if a Case Study enter NA) N/A Conclusion We report an extremely rare case of MPNST of the pancreas with molecular confirmation.

Osteoblastoma Recurring as High-grade Osteosarcoma

Abstract Introduction/Objective Osteoblastoma is a benign, bone-forming neoplasm that presents as a well-circumscribed lesion amenable to excision. The prognosis is good despite a 20% recurrence risk. Malignant transformation is very rare. Osteoblastoma-like osteosarcoma is a rare form of osteosarcoma that shares similar clinical, radiographic, and pathological characteristics Methods/Case Report A 24-year-old female presented with a large palpable mass in the posterior occiput. The lesion progressively enlarged over 2 years, finally becoming symptomatic. Magnetic resonance imaging demonstrated an extradural posterior fossa expansile skull mass measuring 6.0 x 5.7 x 4.7 cm that showed multiple fluid/fluid levels. The mass was resected. Pathology demonstrated a well-circumscribed neoplasm that was cellular and composed of large polyhedral osteoblasts with eccentric oval nuclei and abundant amphophilic cytoplasm. Tumor cells were intimately associated with numerous small interconnecting, irregular bony trabeculae. Scattered mitotic figures of normal configuration were noted. The findings were compatible with an epithelioid osteoblastoma with prominent secondary aneurysmal bone cyst-like changes. The patient was lost to follow-up but presented 3 years later with severe migraines. Imaging demonstrated a large heterogeneous enhancing mass centered about the occipital cranioplasty with both intracranial and extracranial components. Reexcision was performed. Sections showed a well- circumscribed tumor, delineated by a rim of subperiosteal reactive bone, with an epithelioid morphology. However, it also demonstrated areas of necrosis, extensive sheet-like growth, conspicuous mitoses, and cytological atypia not seen in the previous specimen. Therefore, diagnosis of osteoblastoma-like osteosarcoma was rendered after expert consultation. Results (if a Case Study enter NA) NA Conclusion This case highlights the exceedingly rare evolving nature of osteoblastomas and their high-grade transformation potential.

Heterotopic High-Grade Salivary duct Carcinoma Likely Arising within Cervical Lymph Nodes

Abstract Introduction/Objective Salivary duct carcinoma arising in heterotopic salivary gland tissue is an extremely rare occurrence, with less than five cases reported in the literature. We present a unique case of heterotopic high-grade salivary duct carcinoma likely arising within cervical lymph nodes. Methods/Case Report A 56-year-old male presented with enlarged cervical lymph nodes for few months. Physical examination was unremarkable. Computerized tomography (CT) scan of head and neck showed two enlarged level 1B lymph nodes, measuring 1.0 and 1.4 cm, with unremarkable salivary glands. Patient had left cervical level II lymph node biopsy that showed metastatic poorly differentiated carcinoma. Immunohistochemically, the tumor cells were positive for GATA3, cytokeratin 903, androgen receptor, p16 (variable nonspecific), and were negative for TTF-1, p40, p63, ER, PR and NKX3.1, favoring salivary gland ductal carcinoma. Positron emission tomography (PET) CT scan showed a hypermetabolic left submandibular gland and level 2A lymph nodes. Subsequently, the patient underwent left modified radical neck dissection. Sectioning of the submandibular gland revealed no discrete lesions. Multiple, firm to rubbery lymph nodes ranging from 0.4 cm to 2.3 cm, with tan-pink cut surfaces were identified. Microscopic examination showed normal submandibular salivary gland parenchyma. However, eight out of nineteen lymph nodes were positive for metastatic high-grade salivary duct carcinoma comprising tumor cells forming nests and cords with ample eosinophilic cytoplasm, pleomorphic round to oval nuclei and numerous mitotic figures. Several benign and malignant lymph nodes in levels I, II and IV showed heterotopic salivary gland tissue. Immunohistochemical stains for androgen receptor and p40 were positive and negative respectively, supported the final diagnosis of high-grade salivary duct carcinoma. Results (if a Case Study enter NA) NA Conclusion Given the absence of carcinoma in the completely sampled submandibular gland, the origin of the intra- nodal tumor deposits was most likely to be heterotopic salivary gland tissue. This case emphasizes the importance of meticulous pathological sampling required for definitive diagnosis.

The Importance of Pathogenesis: A Molecular Investigation on A Solitary Choriocarcinoma Lung Lesion with No Primary Lesion

Abstract Introduction/Objective We present an exceedingly rare case of metastatic choriocarcinoma to the lung with no primary lesion. Notably, this is the only case where STR molecular studies have been conducted. Methods/Case Report A 43-year-old G1P1001 female with no past medical history presents with severe shortness of breath, left-sided back, and chest pain for severe shortness of breath, left sided back and chest pain. Patients pregnancy test was positive with a B-hCG of 17944 u/L. Transvaginal ultrasound was negative for IUP. CTAP showed no masses in the uterine cavity or ovaries. D-dimer was elevated at 623 ng/ml. However, CTA chest was negative for pulmonary emboli but revealed a RLL mass measuring 2.6 x 2.5 cm x 2.9 cm with lobulated areas suspicious for vascular structures and connection to the right pulmonary vein. Patient was treated with a complete right lower lobectomy. An endometrial biopsy was performed and was negative for malignancy with no significant findings. Grossly, the mass was well-circumscribe, hemorrhagic, and necrotic, measuring 3.5 cm. Microscopically, the malignant cells had highly pleomorphic and hyperchromatic nuclei. There were also multiple multinucleated cells and mitotic figures present. Some of the cells had nested architecture leading to us to suspect a pleomorphic lung adenocarcinoma with choriocarcinomatous differentiation. We performed IHC staining that demonstrated strong positivity of AE1/AE3, CK7, hCG and a high Ki-67 index. The neoplastic cells also had focal p63 and p40 positivity. Furthermore, TTF1 and SALL4 were both negative. This staining pattern as well as patient’s clinical history of no gynecological lesion, lead us to favor lung adenocarcinoma with choriocarcinomatous differentiation. However, due to the abundance of syncytiotrophoblastic and trophoblastic cells, metastatic choriocarcinoma could not be ruled out. Therefore, the case was sent out for external consultation and Short Tandem Repeat (STR) molecular testing. Surprisingly, the STR testing results showed some STR of paternal origin indicating a metastatic gestational choriocarcinoma. The patient’s surgery was highly successful and lead to a down trending of b-hCG from 17944 to 1768 after removal. Results (if a Case Study enter NA) NA Conclusion Performing STR testing was pivotal in this case as it revealed the presence of DNA of paternal origin, providing crucial evidence that the tumor was of gestational origin, guiding the diagnosis towards metastatic gestational choriocarcinoma.

EVERY KERATIN-POSITIVE MALIGNANT TUMOR IN THE ADRENAL GLAND IS NOT METASTATIC CARCINOMA- A CASE REPORT

Abstract Introduction/Objective Angiosarcoma is a rare subtype of sarcoma arising from the vascular endothelial cells. Primary adrenal angiosarcoma (PAA) is an exceedingly rare entity, with only 53 cases documented in the literature so far. Methods/Case Report A 78-year-old female presented with left upper quadrant abdominal pain and early satiety. A computed tomography scan of the abdomen revealed a 15 x 13 x 16 cm, heterogeneous enhancing mass with interspersed calcifications, possibly originating from the left adrenal gland. The mass was found to be displacing the spleen and the left kidney. An ultrasound-guided biopsy of the mass was inconclusive, and the patient subsequently underwent resection of the left retroperitoneal mass, left adrenalectomy, splenectomy, and left partial nephrectomy. Gross examination revealed a slightly ruptured, red-brown mass (19.5 x 12.7 x 12.6 cm, 1784g), which was serially sectioned to reveal diffusely hemorrhagic and necrotic cut surfaces. On microscopic examination, the tumor was almost entirely hemorrhagic and necrotic, with a few viable areas that were composed of solid sheets of markedly pleomorphic epithelioid cells with a high nuclear-cytoplasmic ratio, prominent nucleoli, and increased mitotic figures. There were also a few ectatic vascular spaces lined by these markedly pleomorphic epithelioid cells. Immunohistochemical stains of the tumor cells showed positive results for cytokeratins, CD31, ERG, and friend leukemic integration 1 (FLI-1), while Inhibin and SF-1 were negative. A diagnosis of epithelioid angiosarcoma was rendered. Results (if a Case Study enter NA) NA Conclusion PAA can be difficult to diagnose since it is rare, and thus it is not typically considered in the initial differential diagnosis. Most PAA have an epithelioid morphology, and they frequently test positive for cytokeratins. Biopsy diagnosis can also be challenging, as the mass may exhibit extensive necrosis and hemorrhage. Considering its rarity, large adrenal masses with heterogeneous features on imaging PAA should be considered as a differential diagnosis.

Exploring Immunohistochemical Profiling in High-Grade Endometrial Stromal Sarcoma - A Case Study

Abstract Introduction/Objective High grade endometrial stromal sarcoma (HGESS) is a rare and aggressive tumor of endometrial stromal origin comprising about 0.2% of all uterine malignancies. It is often misdiagnosed preoperatively as uterine leiomyoma, leiomyosarcoma or endometrial carcinoma due to lack of well defined clinical and radiological features. We present an unusual case of HGESS with fibroid uterus and abnormal vaginal bleeding. Methods/Case Report A 73-year-old female with a past medical history of uterine fibroids presented with abnormal vaginal bleeding for 6 months. Her MRI uterus revealed enlarged uterus measuring 6.8 X 9.9 X 9.3 cm, multiple fibroids, and endometrial thickness of 4 mm. Hysteroscopic dilation and curettage revealed endometrial polyp and submucosal fibroid. Histopathology of submucosal fibroid revealed loosely cohesive tumor cells with high nuclear/cytoplasmic ratio, scant cytoplasm, and large prominent nucleoli, arranged in solid sheets with myxoid stroma. No glandular formation was identified. Tumor cell necrosis, bizarre tumor cells, and markedly increased mitotic activity, including atypical mitotic figures were present. Immunohistochemistry (IHC) revealed tumor cells diffusely positive for smooth muscle actin, CD10, p53, negative for AE1/AE3, CK7, cam5.2, EMA, ER, PR, desmin, and caldesmon. Ki-67 labels close to 50% of the tumor cells. Combined morphologic and IHC features favored the diagnosis of high-grade sarcoma, including leiomyosarcoma and HGESS. However, the possibility of carcinosarcoma (CS) could not be ruled out. Patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Final histopathological diagnosis revealed HGESS, pT1b. Lack of carcinomatous component and negative IHC staining for CK7, CAM 5.2, AE1/AE3 ruled out CS. IHC showed tumor cells diffusely positive for CD10, actin, desmin and CD 56, focally positive for caldesmon, cyclin D1 and CD 117 and negative for DOG 1, further supporting the diagnosis for HGESS over leiomyosarcoma. Results (if a Case Study enter NA) NA Conclusion Definitive diagnosis of HGESS is achieved through histology and IHC. An appropriate panel of IHC markers is essential to differentiate between endometrial stromal tumors from leiomyosarcoma and CS. Accurate diagnose of this rare clinical entity is critical especially in its initial stages owing to its poor prognosis and aggressive nature.

Pediatric Eyelid Cutaneous Horns: A Case Series and Literature Review

Purpose: To describe the clinical and histopathologic features of pediatric eyelid cutaneous horns.Design: Retrospective observational case series and review of literature.Subjects: Five pediatric patients with eyelid cutaneous hornsMethods: Five cases with eyelid cutaneous horns were retrospectively identified using departmental databases. Patients’ records were analyzed for demographic data, clinical appearance, histologic findings, and clinical course. An excisional biopsy of the lesion was performed in 3 patients. The remaining 2 patients were managed conservatively.Main Outcome Measures: Clinical outcome and histopathologic evaluation with emphasis on excluding malignancy.Results: All 5 cutaneous horn lesions resolved surgically or conservatively. The average age at presentation was 6.6 years (range 5-11 years). Clinically, 4 lesions were preceded by a hordeolum or chalazion and all excised lesions had benign features on histologic examination. Mitotic figures or atypia were not observed. None of the patients developed recurrence during the follow-up period ranging from 1 to 96 months.Five previous reports of five cases were found on review of the literature. Our case series doubles this number to support the benign nature of these lesions in children.Conclusions: Pediatric eyelid cutaneous horns are closely related to eyelid margin inflammatory disease and appear to follow a benign course. This contrasts with the adult population where cutaneous horns are frequently associated with neoplasia.

6530 A Case of Lymphocytic Hypophysitis Followed by Acromegaly

Abstract Disclosure: L. Medina Mora: None. S. Htoo: None. A. Sanchez Ruiz: None. M. Harshan: None. M. Liu: None. Introduction: Acromegaly, a disorder with an estimated incidence of 0.28-0.4 cases per 100,000 individuals, is characterized by overproduction of growth hormone. Features include acral enlargement, frontal bossing, macrognathia, headaches, and hyperhidrosis. Comorbidities include hypertension, sleep apnea, type 2 diabetes, and cardiomyopathies. Hypophysitis, with an incidence of 1 in 9 million individuals, is an even rarer condition that involves pituitary gland inflammation. It can often lead to hormonal dysfunction and compression of surrounding structures. It is extremely rare for both acromegaly and hypophysitis to occur in the same individual. In this case report, we present a patient who developed lymphocytic hypophysitis followed by acromegaly. Case Report: A 58-year-old woman with a history of hypertension and lymphocytic hypophysitis (discovered during a workup of headaches without hormone derangement) returned to the clinic two years after complaining of progressive enlargement of her hands and feet, fragmented sleep, insomnia, and coarsening of facial features. She was found to have elevated IGF-1 (886 ng/mL; reference range: 48-235 ng/mL) and growth hormone levels (86.9 ng/mL; reference range: 0.12-9.88 ng/mL). An MRI showed a 2.9 x 3.2 x 3.8 cm suprasellar/sellar mass causing pressure on the optic chiasm, hypothalamus, third ventricle and midbrain. The patient underwent transsphenoidal resection (TSR), which was incomplete because the tumor was located behind the pituitary gland, followed by a right craniotomy to remove the remaining tumor. The tumor specimen stained positive for GH and PIT 1, exhibiting elevated proliferative indices (&amp;gt;2 mitotic figures per 10HPF, Ki-67 20%) and p53 labeling (5%). After the surgery, the patient's IGF-1 and GH levels normalized. However, her postoperative course was complicated by third cranial nerve palsy, diabetes insipidus, hypothyroidism, and secondary adrenal insufficiency. Discussion: Although TSR is the first-line treatment for most patients with acromegaly, it may not always result in a complete cure, as almost 50% of patients with macroadenomas do not achieve full surgical recovery. For persistent disease, medical therapy or transcranial surgery may be required. The tumor in this case was atypically proliferative, which was likely why GH and IGF-1 levels rose rapidly, manifesting in acromegalic symptoms in our patient two years after diagnosis of lymphocytic hypophysitis. The natural history of hypophysitis typically progresses from inflammation to fibrosis and subsequently to atrophy of the pituitary cells. This atrophy may cause changes in regulatory hormones that promote tumorigenesis. Therefore, hypophysitis may stimulate adenoma formation leading to acromegaly. More research is needed to characterize the relationship between these two rare entities. Presentation: 6/2/2024

6619 An Unlikely Cause of Oligomenorrhea: Acromegaly Secondary to a Sparsely Granulated, Somatotroph-Lactotroph Adenoma

Abstract Disclosure: S.I. Alicea: None. Y. Wu: None. J. Marquez: None. C.S. Botero Suarez: None. M. Kinaan: None. Introduction: Acromegaly most commonly presents as a pituitary tumor that causes excessive production ofgrowth hormone (GH); and rarely due to excess of GHRH or ectopic production of GH. Approximately 15% of surgically removed pituitary adenomas represent GH-producing neoplasms, and about 5% are bihormonal, secreting both GH and prolactin (PRL). We present a case of an unexpected presentation of oligomenorrhea which ended up with the diagnosis of acromegaly secondary to plurihormonal mixed somatotroph-lactotroph sparsely granulated adenoma. Case Description A 32-year-old female with history of prediabetes was referred to our clinic by her gynecologistfor evaluation of oligomenorrhea which was initially attributed to polycystic ovarian syndrome.She reported menarche at age 10 and has experienced irregular menses and periods of amenorrhea over the years. Physical exam revealed macroglossia, a widened thickened nose, acanthosis nigricans in the neck skin folds, facial hair thickening, and significant thickening of all fingers, toes and soft tissues. Given physical exam findings, we evaluated the patient for acromegaly and lab testing revealed markedly high IGF I, mildly elevated prolactin, and hemoglobin A1C of 5.7%. An MRI of the brain with IV contrast revealed a heterogeneously enhancing pituitary macroadenoma measuring 2.9 x 2.9 x 2.2 cm with suprasellar extension resulting in mass effect on the optic chiasm without definite cavernous sinus extension. She was started on Cabergoline 0.5mg twice weekly temporarily and underwent pituitary transsphenoidal resection. Pathology results revealed tumor cells that were positive for Chromogranin and Cam5.2. About 10% of cells showed immunoreactivity for Prolactin and negative for TSH, ACTH, FSH, LH and immunostains. There was also weak focal (about 2%) immunoreactivity for GH. Occasional mitotic figures were present. The MIB-1 proliferation index was 3%. The reticulin stain demonstrates loss of acinar architecture, supporting the diagnosis. Aside from transient sodium fluctuations consistent with triphasic response, she had no long-lasting postoperative complications. One month after her surgery, her IGF I level and hemoglobin A1C are trending down and she reports symptomatic relief. She continues follow up in our clinic. Discussion This patient has acromegaly secondary to a mixed somatotroph-lactotroph sparsely granulated adenoma. Sparsely granulated adenomas are more common in younger populations, can be more aggressive, and are less responsive to somatostatin analogs. Early detection and treatment is imperative in the prevention of complications secondary to the disease. Our case will closely examine the differences in the clinical, prognostic, and pathologic features of sparsely- vs. densely granulated adenomas. We will also discuss the effects of acromegaly on gonadal function. Presentation: 6/1/2024

Concomitant melanoma and keratoma affecting the equine digit: clinical, pathological, and long-term follow-up findings

BackgroundThis case report details a long-term follow-up of a hoof melanoma with dermo-epidermal activity (resembling Spreading Superficial Melanoma (SSM)) in a bay horse with a history of a right front hoof keratoma. Melanomas involving the horse's foot are seldom reported and usually diagnosed as anaplastic melanomas based on signalment and post-mortem examination. The clinical-pathological characteristics of the foot melanoma in this bay horse are consistent with SSM-like described in humans, which is considered an intermediate malignant tumour attending their biological behaviour. However, a definitive diagnosis is limited by the single case and the lack of references in horses.Case presentationA 12-year-old bay Andalusian gelding underwent keratoma removal on the lateral aspect of the hoof wall. A partial resection of the hoof wall was performed for this purpose. Additionally, a plaque-like, hyperkeratotic pigmented lesion, 2 × 2X0,4 cm in size, was observed at the lateral aspect of the coronary band and was also resected for histopathological examination. Microscopically, a melanocytic tumour, characterised by small nests of large polygonal or epithelioid cells infiltrating the basal and suprabasal epidermis, the dermo – epidermal junction, and the superficial dermis, was observed. The neoplastic cells exhibited large euchromatic nuclei, prominent nucleoli, moderate pleomorphism and 4 mitotic figures per 2,37mm2; variable amounts of dark granules (melanin) were present in the cytoplasm, as well as in numerous peritumoral macrophages. The immunophenotype of the tumour cells was PNL2 + + + , S100 + + , AE1/AE3-. A diagnosis of melanoma with dermo-epidermal junction and marked intraepidermal activity (consistent with superficial spreading melanoma) was made.A magnetic resonance imaging (MRI) performed, revealed no further invasion into surrounding structures. Treatment was based on surgical resection and multiple local chemotherapy sessions with cisplatin were applied. The biopsies obtained after treatment showed partial regression of the tumour and different stages of healing. After 26 months of follow-up, there was no signs of malignant spreading into surrounding structures including the pedal bone and distal metastasis but a dark – coloured area persists over the lateral aspect of the coronary band.ConclusionsThis case presents a concomitant keratoma and melanoma with dermo – epidermal activity, resembling a spreading superficial melanoma. After a follow – up of 26 months the horse remains healthy and sound providing new information for clinicians and pathologists. Despite the poor prognosis associated with foot malignant melanocytic tumours, it is important that an early and accurate diagnosis is reached through different diagnostic modalities such as advanced imaging techniques and histopathology. Additionally, these findings demonstrate that the current classification and prognosis for equine foot melanomas are insufficient.