Pale Cytoplasm Research Articles

Clinicopathological characteristics of low-dose methotrexate-induced epidermal dysmaturation: A study of 22 patients.

Erosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low-dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations. A database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low-dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS. Patients were predominantly female with a mean age of 69.1years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes. This study proposes clinicopathological criteria for the diagnosis of MTX-associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life-threatening progression.

Conjunctival keratoacanthoma: a clinical and histopathological case series

ObjectiveTo present a series of conjunctival keratoacanthomas and provide clinical, histopathological, immunohistochemical, and imaging results that characterize this rare entity. MethodsA retrospective chart review of records from 2005 to 2023 from the Florida Lions Ocular Pathology Laboratory was conducted. Nine patients with histologically proven conjunctival keratoacanthoma were identified. Data extracted includes demographics, clinical history, diagnostic testing, histopathological and immunohistochemical testing, treatment modalities, and recurrences. ResultsPatients’ mean age was 55.2 ± 21.1 years (range: 22–83). 77.8% (7/9) of patients were male. 55.6% (5/9) were Hispanic. 55.6% of lesions (5/9) were in right eyes. 55.6% of lesions (5/9) were on the temporal, bulbar conjunctiva. The lesions were rapidly growing, with mean onset time of 4.71 ± 3.30 weeks (range: 2–12). High-resolution anterior segment optical coherence tomography of three lesions revealed hyper-reflective, thickened epithelium with abrupt transition between normal and abnormal epithelium. Underlying disorganized subepithelial tissue was noted. However, the overlying abnormal epithelium caused considerable shadowing, which obscured subepithelial structures. Prominent, keratin-filled, cup-shaped lesions with faulty maturational sequencing that extend full thickness, variably pale cytoplasm, and foci of dyskeratosis and hyperkeratosis were present on all lesions’ histopathology.All lesions were surgically excised, but two demonstrated partial spontaneous resolution before surgery. Two patients were lost to follow-up; the remaining seven had no signs of recurrence at a of mean of 36.9 ± 45.4 months (range: 3 to 141 months) of follow-up. ConclusionsConjunctival keratoacanthomas are rare lesions of the ocular surface with distinct clinical, histopathologic, and diagnostic features.

Extramedullary Paravertebral Mass: An Unusual Presentation of Hairy Cell Leukaemia.

Hairy cell leukaemia (HCL) is an uncommon, indolent, B-cell, lymphoproliferative disorder typically involving peripheral blood, spleen and bone marrow. It is commonly presenting with pancytopenia, monocytopenia and massive splenomegaly, while accounting for 2% of lymphoid leukaemias. Cases of extranodal lesions caused by HCL are rare, although these have been reported. Here, we report a case of HCL presenting as a paravertebral mass without systemic involvement. A 58-year-old man was admitted to our hospital due to progressive difficulty walking for a month, without any other symptoms. Blood examination noted mild anaemia with Hb=12.6 g/dl and mild thrombocytopenia of 140,000/μl. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging demonstrated a T6 posterior paravertebral mass lesion, extending into the spinal canal with metastatic bone lesions along the thoracic and lumbar spine. Further imaging study with CT indicated mild splenomegaly (13.4 cm) and an enlarged abdominal lymph node (3.5 cm) near celiac trifurcation. A core-needle biopsy from the paravertebral mass was performed. Results showed small-sized cells with round or oval nuclei, and pale cytoplasm with immunophenotype: B-cell origination with CD20+, Cyclin D1+, DBA.44+, Annexin+ and BRAF+, indicative of HCL. Hairy cell leukaemia (HCL) is relatively uncommon, accounting for 2% of all leukaemia cases.Extramedullary and skeletal involvement in HCL is rare and shares morphological characteristics with other peripheral small B-cell lymphoma neoplasms.Spine biopsy is essential for diagnosis in these cases, since it is always helpful to narrow the differential diagnosis.Correct diagnosis is essential for treatment of HCL and leads most patients to clinical remission and sometimes long-term cures.

ERβ activation improves nonylphenol-induced depression and neurotransmitter secretion disruption via the TPH2/5-HT pathway

The aim of this study is to investigate the role of estrogen receptor β (ERβ) in nonylphenol (NP) - induced depression - like behavior in rats and its impact on the regulation of the TPH2/5-HT pathway. In the in vitro experiment, rat basophilic leukaemia cells (RBL-2H3) cells were divided into the four groups: blank group, NP group (20 μM), ERβ agonist group (0.01 μM), and NP＋ERβ agonist group (20 μM＋0.01 μM). For the in vivo experiment, 72 adult male Sprague-Dawley rats were randomly divided into following six groups: the Control, NP (40 mg/kg) group, ERβ agonist (2 mg/kg, Diarylpropionitrile (DPN)) group, ERβ inhibitor (0.1 mg/kg, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl) phenol (PHTPP)) group, NP+ERβ agonist (40 mg/kg NP ＋ 2 mg/kg DPN) group, and NP+ERβ inhibitor (40 mg/kg NP + 0.1 mg/kg PHTPP) group, with 12 rats in each group. Each rat in drug group were given NP by gavage and/or received a single intraperitoneal injection of DPN 2 mg/kg or PHTPP 0.1 mg/kg. Both in vivo and in vitro, NP group showed a decrease in the expression levels of ERβ, tryptophan hydroxylase (TPH1), and tryptophan hydroxylase-2 (TPH2) genes and proteins, and reduced levels of DA, NE, and 5-hydroxytryptophan (5-HT) neurotransmitters. RBL-2H3 cells showed signs of cell shrinkage, with rounded cells, increased suspension and more loosely arranged cells. The effectiveness of the ERβ agonist stimulation exhibited an increase exceeding 60% in RBL-2H3 cells. The application of ERβ agonist resulted in an alleviation the aforementioned alterations. ERβ agonist activated the TPH2/5-HT signaling pathways. Compared to the control group, the NP content in the brain tissue of the NP group was significantly increased. The latency to eat for the rats was longer and the amount of food consumed was lower, and the rats had prolonged immobility time in the behavioral experiment of rats. The expression levels of ERβ, TPH1, TPH2, 5-HT and 5-HITT proteins were decreased in the NP group, suggesting NP-induced depression-like behaviours as well as disturbances in the secretion of serum hormones and monoamine neurotransmitters. In the NP group, the midline raphe nucleus showed an elongated nucleus with a dark purplish-blue colour, nuclear atrophy, displacement and pale cytoplasm. ERβ might ameliorate NP-induced depression-like behaviors, and secretion disorders of serum hormones and monoamine neurotransmitters via activating TPH2/5-HT signaling pathways.

ALK-Rearranged Renal Cell Carcinoma: A Multi-Institutional Study of 9 Cases With Expanding the Morphologic and Molecular Genetic Spectrum

ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3′ UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.

Cytopathology and clinicopathological correlation of renal neuroendocrine neoplasms

Cytopathology and clinicopathological correlation of renal neuroendocrine neoplasms

Aleukemic leukemia cutis: a rare case report

Leukemia cutis is a rare case disorder characterised by infiltration of neoplastic leukocytes (myeloid or lymphoid) in clinically identifiable cutaneous lesions. It can occur before the onset of hematological presentation of leukemia or during the disease course. The lesions may be highly variable ranging from flesh coloured to violaceous papules, nodules or plaques. A 52-year-old male patient came to the Dermatology Department with multiple asymptomatic erythematous papulonodular lesions involving the face, trunk as well as the extremities from the past 6 months. Systemic examination and counts were normal. On histopathological examination diffuse dense infiltrate of neutrophils and eosinophils throughout the dermis with extension of infiltrate in the interstitium of reticular dermis. Scattered amidst the infiltrate were several large cells with abundant pale cytoplasm and irregular nuclei. Immunohistochemistry was done, radiotherapy was planned and poor prognosis was explained to the patient. The case is being reported due to its rarity and the role of dermatopathologist in early diagnosis.

Cat presumptive zygotes assessment in relation to their development

Abstract The evaluation of oocytes and zygotes, based on their size, shape and morphology, is a valuable tool for predicting subsequent embryo development. While this assessment is non-invasive and made possible with time-lapse monitoring systems, not all the assessment criteria used for zygotes with pale cytoplasm can be used for domestic cat zygotes, which have dark cytoplasm. In this study, feline presumptive zygotes were evaluated for shape, size, and morphology. Measurements were also made of the diameter of the entire zygote, its cytoplasm, and the zona pellucida. Differences in the dataset were assessed using the generalized linear model (GLM) procedure. While there was no relationship between a combination of the tested parameters with the potential for cleavage, blastocyst development, and hatching, the parameters of the shape and size of the entire oocyte, and of the zona pellucida, were related to the development potential. The results presented in this study indicate that the assessment procedure for human zygotes has to be adjusted to be used in the cat model, however the relationship between measurements of the diameter of presumptive feline zygotes and the thickness of zona pellucida with their developmental potential deserves further investigation to optimize assessment of cat presumptive zygotes.

Nodular pyogranulomatous panniculitis due to Leishmania infantum infection in a domestic ferret (Mustela putorius furo)

Leishmaniosis is a vector-borne disease caused by different Leishmania species and transmitted by phlebotomine sand flies under natural conditions in Europe. Scientific information related to Leishmania infantum in dogs is extensive, where less information is available in cats and other companion animals. Recently, first clinical cases of L.infantum infection in domestic ferrrets (Mustela putorius furo) have been described. However, clinical information on leishmaniosis in this species is limited A 15-month-old male neutered domestic ferret was presented with chronic weight loss and the presence of coalescent, erythematous and firm subcutaneous nodules in the ventral abdominal subcutis. A fine-needle aspiration of these nodules was performed and the cytological examination revealed a granulomatous inflammation with the presence of macrophages contained a number of oval organisms with an eccentric nucleus and pale cytoplasm, compatible with Leishmania spp. amastigotes compatible with Leishmania spp. amastigotes. The nodules were surgically excised and histological examination showed a severe multifocal pyogranulomatous panniculitis. Specific immunohistochemistry and qPCR for L. infantum from excised nodules were positive. Additionally, L. infantum was cultured and isolated from the nodules by a fine-needle aspiration. An in-house Western Blot test for L. infantum was performed in serum sample and a positive result was obtained. This is the first reported case of nodular pyogranulomatous panniculitis due to L. infantum infection in a domestic ferret. Further studies are necessary to determine the relevance of domestic ferrets in the transmission of leishmaniosis. The description of new clinical forms of the disease is important as it can assist veterinarians in identifying these new clinical presentations.

Pathologically diagnosed early‐stage gastric adenocarcinoma with enteroblastic differentiation after endoscopic submucosal dissection: A case report

AbstractA 77‐year‐old male patient underwent esophagogastroduodenoscopy at his family doctor, and an easily hemorrhagic depressed lesion was noted near the anterior wall of the gastric antrum. A biopsy revealed moderately differentiated tubular adenocarcinoma > poorly differentiated adenocarcinoma, and the patient was referred to our department for further examination. A 15‐mm 0–IIc lesion is seen near the anterior wall of the gastric antrum and narrow band imaging magnifying endoscopy revealed obscured glandular duct structures and corkscrew pattern vascular structures. We diagnosed the patient with early‐stage gastric cancer [L, Ant, 15mm, cType0‐IIc, cT1(M‐SM1), cN0, cM0, cStage IA] after an esopahogastroduodenoscopy examination at our hospital, and endoscopic submucosal dissection was performed. Histopathological images with hematoxylin and eosin staining showed tumor cells with pale cytoplasm and the immunostaining for alpha‐fetoprotein, sal‐like protein 4, and Glypican3 was positive. The patient was pathologically diagnosed with gastric adenocarcinoma with enteroblastic differentiation, pT1b1 (SM, 0.4 mm), type 0–IIc, 15 mm, UL (‐), Ly0, and V0. Gastric adenocarcinoma with enteroblastic differentiation is one of the representative histological types of alpah‐fetoprotein‐producing gastric cancer. Alpha‐fetoprotein‐producing gastric cancer is infrequent, accounting for at least 3% of all gastric cancers, and is generally highly malignant. Most cases are already advanced upon diagnosis, and finding them in the early stage is rare. Therefore, pathological findings that may indicate the gastric adenocarcinoma with enteroblastic differentiation should be noted even in early gastric cancer.

Abstract 14526: CREG1 Deletion Inhibits Autophagy and Causes Cardiomyocyte Damage Under Nutritional Stress

Introduction: The cellular repressor of E1A-stimulated genes 1 (CREG1) is a small, highly conserved glycoprotein ubiquitously expressed in mammalian tissues. It localizes in the endosomal-lysosomal compartment and promotes lysosome biogenesis and acidification. The goal of the current study was to elucidate the physiological function of CREG1 in the mouse heart. Hypothesis: We hypothesized that deletion of Creg1 would result in pathological cardiac remodeling following nutritional stress. Methods: We generated whole-body and cardiomyocyte-specific Creg1 KO mouse lines via mating Creg1 fl/fl mice with UBC-Cre-ERT2 and Myh6-Cre mice, respectively. Mice were fasted for 16-40 hours, and hearts were evaluated by H&E staining, immunofluorescence, electron microscopy, and biochemical analysis. Knockout mice were compared to within-litter controls. Results: Under ad lib feeding, some whole-body knockout mice exhibited myofibril disarray and irregular nuclei in the heart. After prolonged fasting, both whole-body and cardiomyocyte-specific deletion of Creg1 resulted in significantly increased intracellular vacuoles, pale cytoplasm, and loss of nuclei in the papillary muscles and interventricular septa ( Figure 1 ). Immunofluorescence staining demonstrated significantly increased size and number of LC3 puncta (an autophagosome marker), and Western blot demonstrated accumulation of LC3II in the Creg1 KO hearts. In Creg1 KO cardiomyocytes, electron microscopy revealed condensed and irregular mitochondria, which lost their registry with myofibers. In addition, mitophagy was impaired and sarcomeric Z-discs were either damaged or obliterated. Conclusion: CREG1 protects the heart from nutritional stress-induced injury, likely through the promotion of autophagic flux.

A primary multiple pleomorphic rhabdomyosarcoma of the heart in an adult dog

BackgroundHeart tumors are rare in dogs. They can be benign or malignant. Clinical signs depend primarily on the location of the tumor and its effect on blood flow.Case presentationAn eleven-year-old crossbreed male dog lethargic and anorectic for previous 3 days was presented to the veterinary clinic. The focused ultrasound assessment with sonograms in trauma (FAST) revealed multiple tumors in the heart which were then confirmed in echocardiographic examination performed by a veterinary cardiologist. Due to the poor general condition and grave prognosis, the dog was humanely euthanized. The autopsy revealed numerous intracardiac tumors in all four heart chambers. No proliferative changes were found in other organs either in thoracic or abdominal cavity. Immunohistochemical examination was performed using formalin-fixed, paraffin-embedded tissue from heart masses. The antibodies against myoglobin, desmin, smooth muscle actin, vimentin, CD34, S100, and pan-cytokeratin (AE1/AE3) were used. Microscopically, the tumor was composed of fascicles of spindle-shaped cells with pale eosinophilic cytoplasm with round, oval, and focally elongated nuclei and one or two prominent nucleoli. The tumor cells showed strong diffuse cytoplasmic immunopositivity for myoglobin and vimentin and focal staining for desmin. Immunostainings for smooth muscle actin-SMA, CD34, pan-cytokeratin, S-100 protein were negative. The immunohistochemical staining pattern confirmed rhabdomyosarcoma.ConclusionsThis is the first description of the primary multiple heart rhabdomyosarcoma in a dog.

Case Report: Cutaneous melanocytic schwannoma with concomitant melanocytoma in a canine

Schwannoma is a nerve sheath tumour arising from differentiated Schwann cells, and melanocytic schwannoma (MS) is a rare variant where the Schwan cells produce melanin pigment. MS is typically associated with spinal nerve roots and there have been only ~20 reports of cutaneous or subcutaneous MS to-date in humans. In canines, there have only been two reports of MS, both associated with spinal root nerves. In this report, we describe a 7-year-old Weimaraner cross breed dog that presented with two pigmented lesions on the eyelids. The lesions were surgically removed and histological analysis revealed well-circumscribed, non-encapsulated, expansile, neoplasms that were displacing most of the dermis and adnexa. The first lesion was composed of spindloid cells arranged in short interlacing streams with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. In areas there were spindle cells arranged in verocay bodies which led to a diagnosis of MS. In contrast, the second lesion was composed of polygonal cells arranged in thick sheets with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. The diagnosis was melanocytoma (which is one of the macroscopic differential diagnoses for MS). Whilst melanocytoma is a commonly occurring cutaneous lesion in canines and surgical removal is considered curative, due to little being known about MS in dogs, the outcome remained guarded, as MS in humans has an unpredictable nature, and recurrence and metastasis have been reported.

Primary Cutaneous Epithelioid Mesenchymal Tumor With a Novel ATP2B4::GLI1 Gene Fusion.

GLI1 gene alterations (rearrangement or amplification) have been found in several bone and soft tissue tumors including pericytic tumors, gastric plexiform fibromyxoma, gastroblastoma, and a various group of epithelioid tumors with regional recurrence or distant metastasis. In this article, we describe a case of primary cutaneous epithelioid mesenchymal tumor harboring hitherto not reported ATP2B4::GLI1 gene fusion. A 42-year-old man presented with a growing firm lesion on the left postauricular scalp. Microscopically, the shave biopsy specimen revealed a dermal-based nodular proliferation of relatively monotonous epithelioid cells with round to ovoid nuclei and pale eosinophilic cytoplasm, accompanied by prominent stromal vasculature. Significant cytologic atypia, necrosis, and mitotic activity were absent. The tumor cells were partially positive for CD34 and S-100 protein, but were negative for other markers, including SOX-10, keratins, and myogenic markers. An ATP2B4::GLI1 gene fusion was identified by next-generation sequencing. Array CGH was also performed, but it did not show relevant chromosomal copy number changes. Awareness of this rare cutaneous tumor, and thus, reporting of additional cases is necessary for further delineating its full clinicopathologic spectrum.

Palisading Adenocarcinoma: A Morphologically Unique Salivary Gland Tumor With a Neuroendocrine-like Appearance and a Predilection for the Sublingual Glands of Women.

Adenocarcinoma, not otherwise specified (NOS) is a heterogenous group of salivary gland tumors that likely contains distinct tumors that have not yet been characterized. Indeed, in recent years, cases previously diagnosed as adenocarcinoma, NOS have been recategorized into novel tumor designations such as secretory carcinoma, microsecretory adenocarcinoma, and sclerosing microcystic adenocarcinoma. We sought to describe a distinctive, hitherto-undescribed salivary gland tumor encountered in the authors' practices. Cases were pulled from the surgical pathology archives of the authors' institutions. Histologic, immunohistochemical, and clinical findings were tabulated, and targeted next-generation sequencing was performed on all cases. Nine cases were identified, arising in 8 women and 1 man ranging from 45 to 74 years (mean, 56.7y). Seven tumors (78%) arose in the sublingual gland, while 2 (22%) arose in the submandibular gland. The cases shared a distinctive morphologic appearance. They were biphasic, with ducts scattered among a predominant polygonal cell with round nuclei, prominent nucleoli, and pale eosinophilic cytoplasm. These cells were arranged as trabeculae and palisaded as pseudorosettes around hyalinized stroma and vessels, resembling a neuroendocrine tumor. Four of the cases were well-circumscribed, while the remaining 5 showed infiltrative growth including perineural invasion in 2 (22%) and lymphovascular invasion in 1 (11%). Mitotic rates were low (mean, 2.2/10HPFs); necrosis was absent. By immunohistochemistry, the predominant cell type was strongly positive for CD56 (9 of 9) and variably positive for pan-cytokeratin (AE1/AE3) (7 of 9) with patchy S100 (4 of 9), but negative for synaptophysin (0 of 9) and chromogranin (0 of 9), while the ducts were strongly positive for pan-cytokeratin (AE1/AE3) (9 of 9) and CK5/6 (7 of 7). Next-generation sequencing did not reveal any fusions or obvious driver mutations. All cases were resected surgically, with external beam radiation also done in 1 case. Follow-up was available in 8 cases; there were no metastases or recurrences after 4 to 160 months (mean, 53.1mo). A dual population of scattered ducts with a predominance of CD56-positive neuroendocrine-like cells characterizes a unique salivary gland tumor which is often encountered in the sublingual glands of women, for which we propose the term "palisading adenocarcinoma." Although the tumor was biphasic and had a neuroendocrine-like appearance, it lacked convincing immunohistochemical evidence of myoepithelial or neuroendocrine differentiation. Although a subset showed unequivocally invasive growth, this tumor appears to behave in an indolent manner. Moving forward, recognition of palisading adenocarcinoma and its separation from other salivary adenocarcinomas, NOS will facilitate a better understanding of the characteristics of this previously unrecognized tumor.

Follicular Thyroid Adenoma with Papillary Architecture

A 23-year-old woman underwent left thyroid lobectomy and isthmusectomy for a 2 cm diameter firm mass on the left side of the neck that was also visualized on ultrasonography. The specimen consisted of a 22-gram thyroid gland composed of the left lobe, isthmus and a pyramidal lobe. Cut section of the left lobe showed a 3.5 cm diameter solitary, discrete and encapsulated mass with a tan lobulated and solid cut surface. The rest of the thyroid tissues had red-brown meaty cut surfaces.
 Microscopic section shows a follicular-patterned proliferation enclosed by a thin fibrous capsule with frequent Sanderson polster-like papillary excrescences. (Figures 1 and 2) Both the follicular and the papillary structures are lined by cuboidal to columnar follicular epithelial cells that had ample eosinophilic to pale cytoplasm and uniformly sized, minimally enlarged, generally round, and monolayered nuclei without nuclear grooving, folds, pseudoinclusions, and chromatin clearing. There are no mitotic figures seen. Some of the papillary structures have delicate vascular cores. (Figure 3) There are no psammoma bodies noted. The follicles contain variable amounts of pale eosinophilic colloid ranging from colloid-poor crowded follicles to those with ample colloid that have frequent peripheral scalloping. (Figure 4) Exhaustive sections failed to disclose capsular or vascular invasion. Based on the microscopic features, a diagnosis of follicular adenoma with papillary architecture was rendered.

Meningothelial hamartoma on the forehead of a young cat

A 1 year and 2-months-old neutered male cat underwent surgical resection of a cutaneous nodule on the midline of the forehead that had been present since approximately 6 months of age. Histopathologically, the nodule was composed of interlacing collagenous fibres interspersed with varying numbers of spindloid cells with round to oval nuclei and moderate to abundant amounts of pale eosinophilic cytoplasm. Similar to meningothelial cells, the spindloid cells were immunopositive for vimentin, neuron-specific enolase, E-cadherin and somatostatin receptor 2. Based on these findings and the absence of nuclear atypia and mitotic figures, the nodule was diagnosed as meningothelial hamartoma. Although cases of cutaneous meningioma have been reported, this is the first report of meningothelial hamartoma in a domestic animal.

VIM::KMT2A-rearranged sarcomas: A report of two new cases confirming an entity with distinct histologic features.

The recently described KMT2A-rearranged sarcomas are rare emerging entities where the KMT2A gene fuses with YAP1 and, less commonly, VIM, resulting in two distinct morphologies. Unlike the sclerosing epithelioid fibrosarcoma-like features that characterize tumors with KMT2A::YAP1 fusions, VIM::KMT2A-rearranged sarcomas are more uniformly cellular and lack the extensively sclerotic background seen in the former. Most tumors behave aggressively with metastases on presentation. Here, we describe the clinicopathologic and molecular findings in two additional cases of VIM::KMT2A rearranged sarcomas that arose in the deep soft tissues of adult males. Both tumors were composed of hypercellular fascicles of uniform spindle cells with pale eosinophilic cytoplasm and ovoid nuclei. The stroma had scant delicate collagen with occasional thin-walled ectatic blood vessels and perivascular hyalinization. Immunohistochemical studies showed an unspecific staining pattern with diffuse positivity for CD99 and BCL2 and variable staining for S100 protein. RNA-sequencing detected the presence of VIM::KMT2A gene fusion involving VIM exon 4 and KMT2A exon 2 in both cases. Sarcomas with VIM::KMT2A gene fusions seem to have sufficient morphologic features to warrant distinction from KMT2A-rearranged sarcomas with YAP1 partner. Without the benefit of molecular testing, these tumors pose a diagnostic challenge due to their lack of specific immunohistochemical profile and great morphologic overlap with other monomorphic spindle cell neoplasms.

Primary Mucosal Melanoma of the Penile Urethra: A Case Report of an Extremely Rare Disease with a Unique Molecular Profile

Primary melanomas of the penis are extremely rare, accounting for 0.18% of all melanomas and less than 2% of all primary penile malignancies. We present a case of primary mucosal melanoma of the penile urethra in an 82-year-old man. His partial penectomy revealed sheets of spindling and epithelioid tumor cells with pale eosinophilic granular cytoplasm and indistinct cell borders, which invaded into the corpus spongiosum. Multi-foci of melanoma in situ were identified at the mucosal surface of the urethra meatus. Both positron emission tomography (PET) and magnetic resonance imaging (MRI) scan one month after the partial penectomy showed no evidence of metastatic disease. Five months later, an F18-fluorodeoxyglucose-PET/computed tomography scan demonstrated mildly increased F18-fluorodeoxyglucose avidity along the ventral penis and a marked avidity of a right inguinal lymph node. Subsequent excision confirmed an ulcerated melanoma and a metastatic melanoma in one inguinal lymph node, respectively. Molecular analysis revealed a unique BRAF c.1780G>A mutation, resulting in the D594N alteration, which is the first report in penile urethral melanoma. The patient was miserable from the first infusion of immunotherapy (Keytruda), and a PET scan showed that the tumor continued to grow, with extensive metastatic pulmonary disease leading to massive pleural effusion. Unfortunately, the patient died of disease 18 months after his first presentation.

Preen gland of the laughing dove (Streptopelia senegalensis aegyptiaca): Light and electron microscopic analysis.

This work reviews the microscopic anatomy of the preen gland in laughing dove (Streptopelia senegalensis aegyptiaca) using light, scanning, and transmission electron microscopes. The gland possessed two large pea-shaped lobes. The glandular lobules of each lobe were huddled in elliptical, triangle, round shapes, connected with each other by strands of connective tissue septae. The lobule was composed of glandular follicles, each follicle folded and enclosed by a sheath of connective tissue connected with the neighboring ones by interfollicular septae. The gland's parenchyma was coated with a dense connective tissue capsule composed of collagen, elastic, and reticular fibers. The secretory tubules were divided into peripheral tubules and central tubules. The central ones were located close to the major cavity and lined with thin epithelium, whereas the peripheral tubules were adjacent to the capsule and characterized by taller epithelium. The central secretory tubules were lined with four cell layers: flattened basal, large-sized polyhedral intermediate, and secretory cell layers, as well as a degenerative cells layer that formed of small cells with pale cytoplasm and pyknotic nuclei. Variable sizes and shapes of Herbst corpuscles were detected alongside the papillary duct and near the glandular lobe. Transmission electron microscopy view revealed that the cytoplasm of the intermediate cells contained a dense population of mitochondria, while the secretory and degenerative cells contained fewer mitochondria. In conclusion, these structures will be beneficial for understanding the habitat differences of laughing doves. RESEARCH HIGHLIGHTS: Grossly, the preen gland (PG) of the laughing dove formed of two large pea-shaped lobes. The glandular lobule was composed of glandular follicles, each follicle was folded and enclosed by a sheath of connective tissue connected with the neighboring ones by interfollicular septae. The central secretory tubules were lined with four cell layers: basal, intermediate, secretory, and degenerative cell layers. Variable sizes and shapes of Herbst corpuscles were detected alongside the papillary duct and near the glandular lobe of the PG. In transmission electron microscopic analysis, the cytoplasm of the intermediate cells contained a dense population of mitochondria, while the secretory and degenerative cells contained fewer mitochondria.