The Role of Nucleophosmin 1 (NPM1) Mutation in the Diagnosis and Management of Myeloid Neoplasms

Nucleophosmin (NPM1) is a multifunctional protein with both proliferative and growth-suppressive roles in the cell. In humans, NPM1 is involved in tumorigenesis via chromosomal translocations, deletions, or mutation. Acute myeloid leukemia (AML) with mutated NPM1, a distinct diagnostic entity by the current WHO Classification of myeloid neoplasm, represents the most common diagnostic subtype in AML and is associated with a favorable prognosis. The persistence of NPM1 mutation in AML at relapse makes this mutation an ideal target for minimal measurable disease (MRD) detection. The clinical implication of this is far-reaching because NPM1-mutated AML is currently classified as being of standard risk, with the best treatment strategy (transplantation versus chemotherapy) yet undefined. Myeloid neoplasms with NPM1 mutations and <20% blasts are characterized by an aggressive clinical course and a rapid progression to AML. The pathological classification of these cases remains controversial. Future studies will determine whether NPM1 gene mutation may be sufficient for diagnosing NPM1-mutated AML independent of the blast count. This review aims to summarize the role of NPM1 in normal cells and in human cancer and discusses its current role in clinical management of AML and related myeloid neoplasms.

Survival in metaplastic breast carcinoma: A case series

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer (0.20–1.00% of all cases). With a more aggressive clinical course, MBC frequently presents as a triple-negative subtype. OBJECTIVE: To describe a case series, analyzing patients survival in four MBC cases. METHODS: The cases were obtained from 532 medical records of breast cancer patients (0.7% of the total). RESULTS: All patients were female. Mean patient age was 49 years (range: 38–60 years). Mean tumor size was 8.9 cm (range: 3.0–15.5 cm). Mastectomy was performed in three cases. One patient had axillary nodal metastasis. All underwent chemotherapy and three received radiation therapy after surgery. CONCLUSIONS: With a mean follow-up of 36 months (range: 10–60 months), one case had a tumor recurrence (25%). Three patients (75%) died from metastatic disease and one (25%) is still alive and free of disease.

A Case of Primary Squamous Cell Carcinoma of The Thyroid Gland

Primary squamous cell carcinoma of thyroid is a very rare malignant tumor with poor prognosis. It is usually diagnosed as an advanced disease infiltrating adjacent organs, and characterized by aggressive clinical course with an average postoperative survival time of less than 1 year. Recently, we had a 79- year-old woman with a painful neck mass who was diagnosed as primary squamous cell carcinoma of thyroid gland. She underwent total thyroidectomy and selective neck dissection(level Ⅲ, Ⅵ) with no further postoperative managements such as radiation therapy or chemotherapy; she died of poor general condition and pneumonia resulting from rapid progression of the lesion on the 38th day after surgery. We report this case with a review of relevant literatures.

Sclerosing stromal tumor of the ovary a case series and review of literature

Sclerosing stromal tumor of the ovary is a rare benign sex-cord stromal tumor that affects primarily young females. In a series of 6 patients (mean 24,6, median 19 years) findings of 6 MRIs and 1 CT were analyzed. Unilateral tumors ranging from 6 to 8 cm were found in all patients. The tumors were well encapsulated and polylobulated. The morphology was mixed solid and cystic in three and solid in 3 patients. In CT, a hypervascular tumor with centripetal enhancement was seen. In MRI T2WI showed low signal intensity of the solid tissue in all cases and low DWI signal of the solid tissue in high b value DWI in 3 patients. Contrast enhancement was avid with extension from the periphery in all patients. Knowledge of these distinct radiological features of sclerosing stromal tumor is important, as in the O-RADS risk classification system this may be scored as O-RADS 5. Because of its non-aggressive clinical course, preoperative imaging assists to avoid unnecessary extensive surgery and to preserve the patient’s fertility by only resecting the tumor and preserving the ovary. Sclerosing stromal tumor of the ovary presents pathognomonic features in MRI that allow a specific preoperative diagnosis and selecting candidates for fertility-sparing surgery.

Methylation profiling reveals novel molecular classes of rhabdomyosarcoma

Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS. Comprehensive genomic analysis has previously defined the mutational and copy number spectrum for the more common ERMS and ARMS and revealed corresponding methylation signatures. Comparatively, less is known about epigenetic correlates for the rare SC/SRMS or PRMS histologic subtypes. Herein, we present exome and RNA sequencing, copy number analysis, and methylation profiling of the largest cohort of molecularly characterized RMS samples to date. In addition to ARMS and ERMS, we identify two novel methylation subtypes, one having SC/SRMS histology and defined by MYOD1 p. L122R mutations and the other matching adult-type PRMS. Selected tumors from adolescent patients grouped with the PRMS methylation class, expanding the age range of these rare tumors. Limited follow-up data suggest that pediatric tumors with MYOD1-mutations are associated with an aggressive clinical course.

Embryonal Rhabdomyosarcoma with Posttherapy Cytodifferentiation and Aggressive Clinical Course

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents. Embryonal rhabdomyosarcoma (ERMS), its most common subtype, is a malignant soft tissue tumor with morphologic and immunophenotypic features of embryonic skeletal muscle. The histologic findings in ERMS typically include a range of differentiation in rhabdomyoblasts from primitive to terminally differentiated forms, and the latter become more prominent after chemotherapy-induced cytodifferentiation. Several reports have shown therapy-related cytodifferentiation to portend a good prognosis in ERMS. We discuss the case of a pediatric patient who presented with ERMS of the orbit. Although her tumor showed extensive posttreatment cytodifferentiation and several other good prognostic clinicopathologic factors, it pursued an aggressive course, resulting in early metastasis and death. This case represents an unusual course and may be instructive as to the clinicopathologic features impacting prognostication, and ultimately the biology, of this aggressive family of tumors.

Cordoid Meningioma A Case Report

Introduction: Meningiomas are tumors of the central nervous system derived from the arachnoid layer of cells, represent less than 3% of all primary intracranial tumors in children, are prevalent in adolescents, and are rare in younger ages. Pediatric cases represent approximately 1.5% of all intracranial meningiomas, and very few cases show aggressive histology. The WHO classification meningioma divided into three grades: Grade I benign; II, atypical; and III, anaplastic / malignant. Chordoid meningioma grade II / atypical meningioma is a rare subtype, which represents only 0.5% of all meningiomas, have high growth rates, higher recurrence and greater possibilities to invade the brain parenchyma compared with meningiomas benign. One possible explanation for the high recurrence rate may be related to the quality mucoid stroma, which facilitates extension of tumor and makes it difficult to achieve a complete resection, which leads to subsequent recurrence. Case Report: We report the case of male patient 4 years of age diagnosed with meningioma Grade II, with clinic 2 months of evolution who presented progressive neurological deterioration, tumoral exeresis was performed in 3 opportunities and placement system ventriculo peritoneal in the course of 1 month and radiotherapy. Comments: Accurate diagnosis, therefore, assumes importance because these tumors have an aggressive clinical course and high probability of recurrence so knowing the pathological Clinical Aspects of this rare neoplasm is essential for the Treatment and Comprehensive monitoring.

Metastatic plasma cell leukemia to the skin: a case report with review of the literature

Plasma cell leukemia (PCL) is a rare variant of leukemia with an aggressive clinical course and a poor prognosis. The cutaneous involvement in PCL is very rare either at clinical presentation of leukemia, namely “leukemia cutis”, or in the metastatic PCL to the skin. We present a case of eruptive multiple cutaneous nodules in a 56-year-old man with metastatic PCL. Histologically, a diffuse dermal and subcutaneous infiltration of ovoid cells with amphophilic cytoplasm and eccentrically located nucleus consistent with plasmacytoid morphology was observed. Neoplastic cells showed strong immunoexpression for CD138 and CD38 consistent with plasma cells phenotype, and loss of expression of CD56. Kappa light chain restriction similar to the phenotype of his PCL was demonstrated. We suggest that the evaluation of new skin lesions in leukemic patients should include a histopathologic examination to establish the diagnosis as soon as possible and a correct management of the disease.

Adenoid basal carcinoma with adenoid cystic-like features—a rare diagnostic dilemma

Introduction/Objective Adenoid basal carcinoma (ABC) of the cervix is a rare, indolent tumor with no known metastatic potential. The tumor is composed of small nests of bland, basaloid cells, which do not elicit a desmoplastic response within the surrounding stroma. Cystic and clear cell change, as well as glandular differentiation, are not unusual. As such, it is important to differentiate ABC from adenoid cystic carcinoma (ACC), particularly on account of the aggressive clinical course of the latter. We herein present a rare case of ABC with adenoid cystic-like features. Methods/Case Report A 74-year-old woman with an incidental ABC, diagnosed on an excisional procedure performed for a prior diagnosis of a high grade squamous intraepithelial lesion. Subsequent hysterectomy revealed a tumor composed of nests of basaloid cells, extending into the outer third of the cervical wall, but exhibiting no peri- tumoral desmoplasia. Cribriforming associated with increased mitotic activity was focally present and showed increased Ki-67 labeling compared to the solid nests of tumor. PAS special stain highlighted rare pseudolumina with basement membrane-like material. While these features were concerning for an ACC—the lack of any significant cytologic atypia, destructive stromal invasion, and a clinically apparent lesion—was consistent with an ABC with so- called adenoid cystic-like features. Results (if a Case Study enter NA) NA Conclusion Making an accurate diagnosis requires clinicopathologic correlation and awareness of histologic overlap. Additionally, adenoid cystic-like morphology in ABCs is a little-studied phenomenon, which necessitates further research to shed light on potential clinical implications.