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1.
Mod Pathol ; 36(10): 100270, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37422157

ABSTRACT

Mucoepidermoid carcinoma (MEC) is exceedingly rare in the breast, with <45 cases reported in the literature. Although estrogen receptor/progesterone receptor/human epidermal growth factor 2 triple-negative, MEC is characterized as a special subtype of breast carcinoma with significantly better prognosis than conventional basal-type tumors. Cutaneous hidradenoma (HA) is considered a benign adnexal neoplasm showing histomorphologic overlap with MEC. Rare cases of HA have also been reported in the breast, but these are relatively uncharacterized. In this study, we examined the clinicopathologic, immunohistochemical (IHC), and genetic features of 8 breast HAs, in comparison to 3 mammary MECs. All cases were positive for MAML2 break-apart fluorescence in situ hybridization. Eight cases demonstrated a CRTC1::MAML2 fusion, and one MEC harbored a CRTC3::MAML2 fusion; the latter is a novel finding in the breast. Mutational burden was very low, with only one HA exhibiting a MAP3K1 pathogenic alteration. By IHC, both MEC and HA demonstrated cell type-dependent expression of high- and low-molecular-weight keratins and p63, as well as negative to low-positive estrogen receptor and androgen receptor. Smooth muscle myosin and calponin highlighted an in situ component in the 3 cases of MEC; expression of these myoepithelial markers was negative in HAs. Additional distinguishing characteristics included the growth pattern and tumor architecture, the presence of glandular/luminal cells in HA, and overall higher IHC expression of SOX10, S100 protein, MUC4, and mammaglobin in MEC. Morphologic findings were also compared to a series of 27 cutaneous nonmammary HAs. Mucinous and glandular/luminal cells were identified in significantly more mammary HAs than nonmammary lesions. The findings provide insight into the pathogenesis of MAML2-rearranged neoplasms of the breast, underscore the overlapping genetic features of MEC and HA, and highlight similarities to their extramammary counterparts.

2.
Ann Diagn Pathol ; 63: 152085, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36577186

ABSTRACT

BACKGROUND: Tumor budding (TB) has significant prognostic implication in stage II colorectal cancer (CRC) and is graded based on the International Tumor Budding Consensus Conference (ITBCC) protocol. In the current study, we evaluate tumor budding and its relationship to multiple histologic features in 104 tumors. METHODS: One-hundred four resected CRC cases were retrieved. Tumor bud count and TB grade were compared to the final tumor bud count/TB grade of the tumor per ITBCC protocol. The following high-yield co-features were assessed in each slide: highest T stage, presence of benign mucosa, presence of a precursor lesion, and highest tumor volume. RESULTS: Twenty-nine (28 %) cases had discrepancies between slide TB grade and final TB grade. The least discrepancies were seen in slides with benign mucosa (7 %) and precursor lesions (7 %). Among stage II patients without high-risk features, no discrepancies were observed in slides with benign mucosa. Slides with deepest invasion (rs = 1.000, p = 0.01) and benign mucosa (rs = 0.957, p < 0.001) had the strongest correlation with final tumor bud count in the same stage II subgroup. Similar relationships were observed when comparing final TB grade. Deepest invasion, tumor volume, as well as lymphovascular invasion, when present, also showed strong correlations with final TB grade in the entire cohort (rs = 0.828-0.845, p < 0.001). CONCLUSION: Our study is the first study to evaluate the relationship between TB grade and co-existing histologic features. We highlight the benefit of focusing on slides with high-yield co-features, with the strongest correlation seen in slides with adjacent benign mucosa and precursor lesions.


Subject(s)
Colorectal Neoplasms , Pathologists , Humans , Neoplasm Staging , Prognosis , Colorectal Neoplasms/pathology , Consensus
3.
Cancer Cytopathol ; 131(4): 245-253, 2023 04.
Article in English | MEDLINE | ID: mdl-36522809

ABSTRACT

BACKGROUND: Claudin-4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin-4 versus MOC-31 and Ber-EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens. METHODS: This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine-needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin-4 and compared with those previously stained for MOC-31 and Ber-EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases). RESULTS: None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin-4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC-31 and Ber-EP4, claudin-4 had the highest specificity and PPV (100% for each), followed by Ber-EP4. Claudin-4 showed high sensitivity (93.7%), albeit lower than MOC-31. MOC-31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber-EP4 had the lowest sensitivity (91.6%). CONCLUSIONS: Claudin-4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC-31 and Ber-EP4. Mesothelial lineage can be ruled out when claudin-4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin-4 and Ber-EP4 results in the highest combined sensitivity and specificity.


Subject(s)
Carcinoma , Mesothelioma , Humans , Claudin-4 , Retrospective Studies , Carcinoma/diagnosis , Epithelium/pathology , Mesothelioma/diagnosis , Mesothelioma/pathology , Biomarkers, Tumor , Diagnosis, Differential
4.
Saudi J Biol Sci ; 29(9): 103391, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35942163

ABSTRACT

Background: Tendinopathy or tendon injuries can affect many people, causing a huge impact on their movements and maintaining standing posture. Treatment options include physiotherapy, anti-inflammatory drugs, and alternative medicine. The use of physiotherapy or anti-inflammatory drugs may cause some side effects like pain and liver failure, respectively, therefore, alternative medicine will be a better choice. Method: Tenocytes were isolated from sheep Achilles tendon and used in Alamar blue assay to assess the metabolic activity, proliferation, and viability of tenocytes over 24 hrs. and 48 hrs., using natural and synthetic products [i.e., olive oil, oleic acid, corn oil, Inula viscosa oil, Inula viscosa extract, Nigella sativa oil, naproxen sodium, and paracetamol and LED photobiomodulation]. Furthermore, tenocytes viability was assessed by FDA/PI stain. For migration and healing of a wound, the scratch assay was used. Results: Alamar blue assay over 24 hrs. showed that Nigella sativa oil increased the metabolic activity, proliferation, and viability of tenocytes significantly, while Alamar blue over 48 hrs. showed that oleic acid, LED, and their combination increased these parameters for tenocytes significantly. Olive oil increased the viability of tenocytes significantly using FDA/PI stains. Scratch assay revealed that Inula viscosa oil, Inula viscosa extract, and paracetamol increased tenocyte migration and healing significantly. Conclusion: Nigella sativa oil, olive oil, oleic acid, Inula viscosa oil, and Inula viscosa extract may be used as an alternative therapy for tendinopathy with less side effects.

6.
Mod Pathol ; 35(10): 1349-1361, 2022 10.
Article in English | MEDLINE | ID: mdl-35590107

ABSTRACT

Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.


Subject(s)
Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Carcinoma, Large Cell , Carcinoma, Neuroendocrine , Neuroendocrine Tumors , Breast Neoplasms/genetics , Carcinoma, Large Cell/genetics , Carcinoma, Large Cell/pathology , Carcinoma, Neuroendocrine/pathology , Carrier Proteins , Cell Cycle Proteins , Class I Phosphatidylinositol 3-Kinases/metabolism , Female , Humans , Neuroendocrine Tumors/pathology , Proto-Oncogene Proteins/metabolism , Tumor Suppressor Protein p53/genetics
7.
Virchows Arch ; 480(1): 163-176, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35029776

ABSTRACT

Recent advancements in breast cancer treatment have ushered in a new era of precision medicine. Novel trials have led to the approval of a growing list of personalized therapies and corresponding biomarkers. These advancements have shifted the pathologist's practice into a leading role in the management breast cancer. Understanding the complex algorithms and diagnostic modalities used to assess predictive and prognostic biomarkers is central for quality oncology care. ER and HER2 subcategorize breast cancers into treatment groups under which different biomarkers and therapies are indicated, while they also serve as predictive biomarkers for specific targeted treatments. This review will cover the evolution and latest updates of the CAP/ASCO guidelines relevant to these two important biomarkers in breast cancer. Still evolving concepts such as HER2 heterogeneity, HER2 "low," and HER2-mutated cancers have the potential to continue to change HER2 testing in breast cancers. In addition to ER and HER2, biomarkers used in specific clinical scenarios will be covered. In early-stage ER-positive/HER2-negative disease, multi-gene expression panels (such as OncotypeDX) have emerged as the new standard biomarker when determining if chemotherapy should be added to endocrine therapy. In the more aggressive ER-negative/HER2-positive or triple negative early-stage breast cancers, response to neoadjuvant therapy has proved to be a useful biomarker to help determine if additional therapy should be added for patients with an incomplete response. Ki67 has also recently emerged as a marker that can be used to identify the highest risk ER-positive and HER2-negative cancers if considering adding a cell cycle inhibitor (abemaciclib) to endocrine therapy. Importantly, in the metastatic setting, numerous predictive biomarkers have emerged, including recommendations for germline BRCA mutation testing for all metastatic patients (to determine if PARP inhibitor therapy is an option) and other ER-/HER2-dependent biomarkers such as PD-L1 (for potential immunotherapy in triple negative patients) and PIK3CA mutation status (for potential PI3K inhibitor therapy in ER-positive metastatic patients). Other less common biomarkers of targeted therapy options (e.g., MSI/MMR, TMB, NTRK) as well as comprehensive genomic profiling to identify uncommon targets are also available in the metastatic setting to determine additional treatment options.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Biomarkers, Tumor/genetics , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Humans , Neoadjuvant Therapy , Phosphatidylinositol 3-Kinases , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Triple Negative Breast Neoplasms/pathology
8.
Eur J Pediatr Surg ; 32(2): 191-197, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33513627

ABSTRACT

INTRODUCTION: Diagnosis of very short-segment Hirschsprung's disease (vsHD) by rectal suction biopsy is challenging as its aganglionic zone (AZ) overlaps with physiologic hypoganglionic zone and calretinin-positive mucosal nerves may extend from the transition zone (TZ) into AZ. We studied whether an increasing trend/gradient of calretinin-positive mucosal nerves along the distance from AZ toward TZ aids in diagnosis of HD. MATERIALS AND METHODS: In this study, 46 rectal suction biopsies from non-HD and HD, and 15 pull-through specimens from short-segment HD were evaluated by mucosal calretinin immunostain (CI) and image processing and analysis (IPA) to measure pixel count (PC, the percentage of calretinin stained pixels in the mucosa). Consecutive longitudinal sections of proximal AZ toward distal TZ in HD pull-through specimens were utilized as a vsHD surrogate model. First, we studied variability of mucosal CI in non-HD biopsies along the distance from dentate line. Second, we determined a cutoff point of mucosal CI by IPA that separated non-HD versus HD and applied this cutoff to longitudinal sections from proximal AZ to distal TZ segments in HD pull-through specimens. Third, we studied whether an increasing trend of mucosal CI was universally observed in HD pull-through. RESULTS: Our findings included a significant variability in PC along the biopsy distance in non-HD cases. Positive mucosal CI was found in proximal AZ in 6 (43%) of 14 HD pull-through, among which 1 case lacked submucosal nerve hypertrophy in the proximal AZ. All 14 HD pull-through cases showed an increasing trend/gradient of PC from AZ toward TZ. CONCLUSION: Based on our findings, the presence or absence of mucosal CI positivity and submucosal nerve hypertrophy may not reliably diagnose vsHD in rectal suction biopsy. While we acknowledge that the density of mucosal innervation in variable contexts and anatomical locations is unknown and yet to be explored, our study suggests that an increasing trend of positive mucosal CI from AZ toward TZ by IPA might prove to be a useful tool for the diagnosis of vsHD in the future.


Subject(s)
Calbindin 2/metabolism , Hirschsprung Disease , Biopsy , Hirschsprung Disease/surgery , Humans , Hypertrophy/pathology , Infant , Mucous Membrane/pathology , Rectum/pathology
9.
Dermatopathology (Basel) ; 8(2): 190-201, 2021 Jun 07.
Article in English | MEDLINE | ID: mdl-34200164

ABSTRACT

BACKGROUND: The association between Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) is well established in the literature. A majority of MCCs are known to be associated with Merkel cell carcinoma polyomavirus (MCPyV), which is postulated to be a possible causative agent linking these two entities. We aim to identify the presence of MCPyV in patients with concurrent adjacent MCC and CLL/SLL. METHODS: Archived pathology materials of three cutaneous or surgical excisions with concurrent MCC and CLL/SLL were reviewed. Additional 12-µm sections from paraffin-embedded tissue of these resections were matched with original hematoxylin and eosin-stained slides and used to extract foci from each tumor separately. DNA was extracted from these tissues, and polymerase chain reaction (PCR), utilizing a primer set within a highly conserved "small T" viral DNA region, was done to detect MCPyV. RESULTS: Out of 140 cases of cutaneous or surgical excisions with MCC identified in our electronic medical records (EMR), three had coexisting neighboring CLL/SLL in the same resection specimen. In one case out of three, MCPyV was detected in MCC but not in CLL/SLL. The remaining two cases showed no detection of MCPyV in either MCC or CLL/SLL. CONCLUSION: MCPyV was not concurrently associated with adjacent MCC and CLL/SLL, indicating that it is not driving simultaneous tumorigenesis, at least in a subset of these cases.

10.
Breast J ; 27(9): 723-725, 2021 09.
Article in English | MEDLINE | ID: mdl-34173294

ABSTRACT

Radiation-induced breast angiosarcoma, or secondary angiosarcoma (SAS), is a rare entity with a high risk of metastatic recurrence. Herein, we describe the use of intraoperative fluorescence-based skin angiography to guide surgical resection following a novel immunotherapy-based regimen for SAS resulting in a complete pathological response.


Subject(s)
Breast Neoplasms , Hemangiosarcoma , Neoplasms, Radiation-Induced , Angiography , Breast Neoplasms/surgery , Breast Neoplasms/therapy , Female , Hemangiosarcoma/surgery , Hemangiosarcoma/therapy , Humans , Immunotherapy , Mastectomy , Neoadjuvant Therapy
11.
Appl Immunohistochem Mol Morphol ; 29(4): 305-312, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33264106

ABSTRACT

Yes-associated protein (YAP) is a transcriptional coactivator regulated by autophagy that stimulates colorectal cancer (CRC) progression through activation of epithelial-mesenchymal transition (EMT), represented by tumor budding. The associations between these components in CRC are unknown. Archived surgically resected CRCs with known mismatch repair protein (MMR) status were retrieved (n=81; 2010 to 2016). Electronic medical records were reviewed for clinicopathologic variables including pathologic TNM stage and clinical stage. Tumor budding was graded according to consensus guidelines. Cytoplasmic and nuclear YAP and p62 (autophagy substrate) immunoreactivity were semiquantitatively scored within tumor samples. The Student t test, Fisher exact test, χ2 test, and Spearman correlation coefficient were performed with P<0.05 as a significance level. MMR proficiency (MMR-P) status correlated with high-grade tumor budding. The extent of cytoplasmic YAP staining and pathologic N stage was associated with tumor budding in multivariate analysis. Cytoplasmic YAP expression correlated with higher cytoplasmic p62 expression, suggesting an inverse correlation between autophagy activation and cytoplasmic YAP expression. Nuclear YAP expression correlated with pathologic N stage and clinical stage. A correlation between MMR-P status and tumor budding, combined with correlations between cytoplasmic YAP, tumor budding and p62 raise the possibility of 2 distinct neoplastic pathways concerning autophagy and YAP; one displaying relative activation of YAP and EMT, being commonly observed in MMR-P, and another with less active YAP and EMT, but active autophagy, being commonly seen in MMR-deficient CRC. Nuclear YAP staining could be useful in prognostication.


Subject(s)
Autophagy , Colorectal Neoplasms , DNA Mismatch Repair , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/biosynthesis , YAP-Signaling Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Grading
12.
Cureus ; 12(1): e6825, 2020 Jan 31.
Article in English | MEDLINE | ID: mdl-32181070

ABSTRACT

Histoplasmosis is an endemic fungal infection that can lead to disseminated disease, especially in immunosuppressed patients. Hairy cell leukemia is a rare, slow-growing hematological malignancy. Concurrence of histoplasmosis and hairy cell leukemia is extremely rare. We describe a 69-year-old male who presented with fever, dry cough, pancytopenia, multiple pulmonary nodules, and massive splenomegaly. Histoplasma urinary antigen was positive and disease was confirmed by biopsy of lung lesions. Peripheral smear showed 'hairy cells', and bone marrow biopsy revealed findings of hairy cell leukemia. The patient was treated with intravenous amphotericin, followed by oral itraconazole. After the initial treatment of infection, treatment for hairy cell leukemia was started with cladribine. We will discuss the principles of treating disseminated histoplasmosis in the setting of immunosuppression, and hairy cell leukemia with coexisting infection.

13.
Appl Immunohistochem Mol Morphol ; 28(2): 130-138, 2020 02.
Article in English | MEDLINE | ID: mdl-32044881

ABSTRACT

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that mediates multiple cellular functions such as survival, invasion, and migration. FAK has been found to be over-expressed in various human cancers, including melanoma. FAK molecule has several tyrosine, serine, and threonine phosphorylation sites which have an important regulatory role. Tyrosine phosphorylation of FAK has been extensively studied, however little is known about the role of serine phosphorylation. We sought to examine the frequency and extent of serine-910 phosphorylated FAK (P-FAKSer910) expression in a spectrum of melanocytic proliferations as well as it's correlation with other histopathologic predictors and its effect on patient's survival. Clinicopathologic features and immunohistochemical expression of P-FAKSer910 were evaluated in 147 melanocytic proliferations: 73 primary melanoma (PM), 19 metastatic melanoma (MetM), 2 melanoma in situ, and 53 melanocytic nevi (MN). Higher cytoplasmic intensity predicted better overall survival (OS) in PM (χ=5.69; P=0.034) and was associated with 48% decrease in death risk (HR, 0.52; 95% CI, 0.28-0.95; P=0.036). In contrast, increased nuclear intensity was significantly associated with better disease-free survival (DFS) when stratified by tumor stage Log-rank test, trend of survival (χ=5.83, P=0.015) and independently on multivariate analysis when subcategorized into 3-tier categories (HR, 0.43; 95% CI, 0.18-0.98; P=0.045). Also, Clark's level and tumor-infiltrating lymphocytes (TILS) were independent predictors of DFS. Cytoplasmic intensity correlated inversely with American Joint Commission on Cancer stage in primary melanoma cases as well with vascularity in both primary and metastatic melanoma. Nuclear intensity independently correlated negatively with angioinvasion and TILS when subcategorized to 3 tier system. We found American Joint Commission on Cancer tumor stage, Clark's level, depth, ulceration, TILS, mitosis, angioinvasion, and tumor vascularity predictors of both DFS and OS. There was no significant difference in cytoplasmic or nuclear expression among the major categories of melanocytic proliferation. In this pilot immunohistochemistry-based study, we found P-FAKSer910 expression in melanoma by cytoplasmic intensity to correlate with better OS while nuclear intensity correlated with better DFS.


Subject(s)
Focal Adhesion Kinase 1/biosynthesis , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Melanoma , Skin Neoplasms , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Disease-Free Survival , Female , Focal Adhesion Kinase 1/genetics , Follow-Up Studies , Humans , Male , Melanoma/enzymology , Melanoma/genetics , Melanoma/mortality , Melanoma/pathology , Middle Aged , Phosphorylation , Serine/genetics , Serine/metabolism , Skin Neoplasms/enzymology , Skin Neoplasms/genetics , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Rate
14.
Cureus ; 11(9): e5606, 2019 Sep 09.
Article in English | MEDLINE | ID: mdl-31700719

ABSTRACT

A 49-year-old male presented to his physician with three weeks of dyspnea, dry cough, and fever. He did not respond to antibiotics and corticosteroids. He presented to the emergency department with worsening symptoms, where blood work revealed severe anemia, leukocytosis, thrombocytopenia, and 61% blasts on peripheral smear. Bone marrow biopsy showed acute myeloid leukemia (AML). While the results of other studies were awaited, treatment was begun with 7+3 induction (cytarabine and daunorubicin). Karyotyping returned positive for the BCR-ABL1 fusion gene (Philadelphia chromosome), near-tetraploidy, and 5q deletion. Follow-up bone marrow biopsy revealed residual disease (12% blasts). Re-induction was initiated with 5+2 cytarabine and daunorubicin with the addition of dasatinib. Subsequent bone marrow biopsies revealed minimal residual disease and BCR-ABL on polymerase chain reaction (PCR). The patient was placed on dasatinib maintenance and later switched to nilotinib. This case demonstrates the simultaneous presence of rare cytogenetic abnormalities in AML. It also discusses the successful utilization of tyrosine kinase inhibitors (TKIs) in the treatment of BCR-ABL-positive AML, as there are no established guidelines.

15.
Case Rep Hematol ; 2019: 7348504, 2019.
Article in English | MEDLINE | ID: mdl-31467739

ABSTRACT

Extramedullary disease at the time of diagnosis of multiple myeloma is a rare finding that portends poor prognosis and necessitates aggressive treatment strategies. We present a case of multiple myeloma with extramedullary plasmacytomas of the female reproductive system, thyroid and breasts. The patient was treated with lenalidomide, bortezomib, cyclophosphamide, and dexamethasone. Follow-up PET-CT scans confirmed clinical complete response, and the patient underwent autologous stem cell transplantation. The patient will be continued on lenalidomide and bortezomib maintenance therapy. To the best of our knowledge, simultaneous involvement of these sites has never been reported. The case highlights that there are no established guidelines on the treatment of multiple myeloma with extramedullary disease leading to great variability based on clinician preference. We will also discuss the treatment options and prognosis of multiple myeloma with extramedullary disease.

16.
Eur J Pediatr Surg ; 29(2): 179-187, 2019 Apr.
Article in English | MEDLINE | ID: mdl-29304518

ABSTRACT

PURPOSE: Quantification of calretinin-stained mucosal nerve fibers by image processing and analysis (IPA) may objectively define the transition zone (TZ) of Hirschsprung disease (HD). We tested the utility of IPA as an adjunctive tool in HD. MATERIALS AND METHODS: Calretinin immunostain was performed on 15 HD pull-through specimens, and multiple images were captured from the proximal aganglionic zone, TZ, and probable normal zone (NZ). Pixel count (PC), defined as the percentage of brown-stained pixels in the mucosa, was quantified and plotted against distance from the rectal distal end. To validate the method, PCs from 45 images were compared with three-tiered visual scoring by five pathologists. Results were correlated against pertinent variables, which were retrieved from the clinical record. RESULTS: The PC gradually increased in the TZ toward the proximal resection margin in 10/13 (77%) cases. The PC variation in the probable NZ and around the circumference was substantial by the coefficient of variation. The mean PC of images with a visual score of 1 was less than scores of 2 and 3 by all five (100%) pathologists (p < 0.01). One patient had possible TZ pull-through that was clinically confirmed. CONCLUSION: While the mucosal calretinin staining gradually increases in the TZ, for now, the boundaries of the TZ cannot be accurately defined by mucosal biopsies given the substantial variation of staining around the circumference at the same distance and in the NZ. However, the IPA technique does provide a continuous variable and warrants further utility in HD studies.


Subject(s)
Calbindin 2/metabolism , Colon/metabolism , Hirschsprung Disease/diagnosis , Image Interpretation, Computer-Assisted/methods , Intestinal Mucosa/metabolism , Biomarkers/metabolism , Colon/pathology , Female , Hirschsprung Disease/metabolism , Hirschsprung Disease/pathology , Humans , Immunohistochemistry , Infant , Infant, Newborn , Intestinal Mucosa/pathology , Male , Pilot Projects , Retrospective Studies , Staining and Labeling
17.
Lasers Med Sci ; 34(4): 759-766, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30317401

ABSTRACT

Healthy tendons play an important role in joint movements and subjected to a group of pathologies called tendinopathy due to multiple factors. Tendons have a slowly repairing process due to the low vascularity and cellularity. Treatment options aimed at potentiating the healing response and relieving symptoms. Phototherapy and platelet-rich plasma were novel treatment modalities in tendons based on photobiomodulation and growth factors during healing, and the results were encouraging suggesting calibrating treatment parameters. This study utilizes cell culture to explore the potential effect of light-emitting diode and/or growth factors in the form of platelet-rich plasma (PRP) on the activity of tenocytes isolated from sheep Achilles tendons by measuring the cell metabolism and cell mobility using cell viability and migration assays to proof safety and confirm activity. Results showed that sheep tenocyte-cultured groups treated with 5% platelet-rich plasma alone or combined with 4 J/cm2 light-emitting diode have increased viability significantly when compared to control group after a 48 h, while light-emitting diode treatment has not decreased cell migration significantly when compared with control. Result suggests that using platelet-rich plasma alone or combined with light-emitting diode might have potential to enhance healing response at the conditions applied. PRP could enhance proliferation while LED could enhance migration and proliferation. Further research is needed at longer durations.


Subject(s)
Light , Phototherapy , Platelet-Rich Plasma/metabolism , Tenocytes/radiation effects , Animals , Cell Survival/radiation effects , Cells, Cultured , Models, Biological , Sheep , Tendinopathy/radiotherapy , Wound Healing/drug effects
19.
J Investig Med High Impact Case Rep ; 2(1): 2324709614529416, 2014.
Article in English | MEDLINE | ID: mdl-26425600

ABSTRACT

Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation.

20.
JRSM Short Rep ; 4(10): 2042533313490516, 2013.
Article in English | MEDLINE | ID: mdl-24319578

ABSTRACT

OBJECTIVE: To evaluate the hormone receptor status and human epidermal growth factor receptor 2 (HER2)/neu gene expression among Jordanian women with breast cancer. To classify our patients into molecular subtypes and to correlate the results with age of the patients and tumour grade. DESIGN: Evaluation of estrogen receptor (ER), PR and HER2/neu was done by standard immunohistochemical technique and subclassification into molecular subtypes. SETTING: Jordan University Hospital, Amman, Jordan. PARTICIPANTS: One hundred and ninety-three cases of breast cancer diagnosed at Jordan University Hospital. MAIN OUTCOME MEASURES: Molecular subtypes of breast cancer, age and tumour grade. RESULTS: ALL THE CASES WERE DIVIDED INTO TWO GROUPS: the young age group less or equal 50 years of age and the older age group more than 50 years of age. The cases were subclassified into luminal A, luminal B, basal cell like (BCL) and Her2/neu+. In older age group, the most common subtype was luminal A (72%). In this age group, most of the cases (48%) were of grade II. In younger age group, 47% of the cases were of luminal A subclass. In this age group, 42% were of grade I. CONCLUSIONS: Molecular subtyping of breast cancer is an essential predicting factor of tumour response to hormonal therapy. This fact puts increased stress on the urgent need for the development of reliable and reproducible classification systems.

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