Long-term remission of extramedullary cutaneous relapse of acute myeloid leukaemia (leukaemia cutis) treated with decitabine-venetoclax.

In February 2020, a 74-year-old female was diagnosed with myelomonocytic acute myeloid leukaemia with FLT3 mutation and blasts positive for CD33, BCL-2 and CD68/PGM1. Not responding to a standard Cytarabine-containing regimen plus Midostaurin, the patient achieved a complete remission (CR) of the disease in the bone marrow following a reinduction therapy with high-dose Cytarabine but simultaneously relapsed developing leukaemia cutis with disseminated lesions in 80% of the body surface area. After receiving 10 cycles of Decitabine plus Venetoclax the patient achieved and maintains a continuous CR.

Mycosis Fungoides with Dermal Mucin Deposition: An Unusual Variant of the Most Challenging Primary Cutaneous Lymphoma.

Mycosis fungoides (MF) is defined as an epidermotropic primary cutaneous T-cell lymphoma composed of small-to-medium-sized T lymphocytes with cerebriform nuclei and with a T-helper phenotype. LeBoit first described an unusual variant of MF with dermal acid mucin deposition. Such a variant was still considered in the list of clinicopathological variants of MF by Cerroni and colleagues. We herein report a case of patch-stage MF with abundant papillary dermal mucin deposition in a clinical setting of an erythematous patch on the lower abdomen and thigh.

Colorectal polyposis as a clue to the diagnosis of Cowden syndrome: Report of two cases and literature review.

Cowden Syndrome (CS) is an autosomal dominant disorder characterized by hamartomatous growth in several organs and by an increased risk of malignancies, which makes its recognition essential to undertake risk reduction measures. Although the involvement of gastrointestinal tract is extremely common, awareness of this entity among gastroenterologists appears limited. We report on two unrelated patients: a 46-year-old male and a 38-year-old woman, who were referred to the Genetic Clinic because of the endoscopic finding of multiple colorectal polyps. Despite both displayed striking clinical (and, in the first case, familial) manifestations of Cowden Syndrome (PTEN Hamartoma Tumor Syndrome-PHTS), they had not been recognized before. Diagnosis of PHTS was confirmed by the detection of causative PTEN variants. Pathological examination of the polyps showed multiple histology types: hyperplastic, juvenile, serrated and lymphoid. Hyperplastic polyps analyzed from both patients failed to show BRAF V600E and KRAS codon 12/13 mutations, which provides evidence against their potential to evolve to colorectal cancer through the serrated pathway. We then reviewed the literature on gastrointestinal polyps detected in patients with Cowden Syndrome, in order to provide a comprehensive scenario of presentations: among a total of 568 patients reported in the literature, 91.7 % presented with colon polyps, with 63.0 % having two or more different histological types of polyps; besides, 58.5 % had extra-colonic polyps (located either in stomach and/or in small intestine). Finding multiple polyps with mixed and/or unusual histology should alert gastroenterologists and pathologists about the possible diagnosis of Cowden Syndrome and prompt the search for other manifestations of this condition in the patient.

Pilomatrical Tumor of Low Malignant Potential: A Tumor Between Pilomatricoma and Pilomatrical Carcinoma.

ABSTRACT: We report a case of pilomatrical tumor showing intermediate histological features between pilomatricoma and pilomatrical carcinoma. The lesion recurred twice with the same histological features. Similar cases were was probably called aggressive or proliferating pilomatixoma; we think that the term pilomatrical tumor of low malignant potential is more suitable for this lesions. Excision with wide free margins and follow-up are recommended.

Glycolytic competence in gastric adenocarcinomas negatively impacts survival outcomes of patients treated with salvage paclitaxel-ramucirumab.

INTRODUCTION: For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab. MATERIALS AND METHODS: Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes: HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status. RESULTS: Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples. CONCLUSIONS: Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.

Does transbronchial lung cryobiopsy give useful information in asthmatic patients?

INTRODUCTION: Lung biopsy in asthmatic patients is justified in case of atypical presentations of asthma, when other differential diagnoses, such as hypersensitivity pneumonitis or eosinophilic granulomatosis with polyangiitis, could be possible or for research purposes. AIM: We aim to describe the utility and the safety of TBLC (transbronchial lung cryobiopsy) in asthmatic patients, providing data on the pathological changes occurring in the airways and in the lung parenchyma. METHODS: We reviewed asthmatic patients that underwent TBLC, that eventually had only a final diagnosis of asthma. RESULTS: Three patients were detected. TBLC described pathological abnormalities in peribronchiolar and alveolar spaces already well identified with SLB (surgical lung biopsy); the pathological information provided could be useful to better understand the pathobiology of the disease. Finally, we had no complications, confirming a satisfactory safety profile of TBLC. CONCLUSION: We suggest the potential role of TBLC in asthmatic patients: its safety and its acceptable diagnostic accuracy lead to consider this procedure instead of SLB when histological changes in lung parenchyma are needed for the differential diagnosis. Furthermore, TLBC could be useful for research in the pathobiology of asthma and severe asthma.

Impact of p16(INK4a) immunohistochemistry staining on interobserver agreement on the diagnosis of cervical intraepithelial neoplasia.

OBJECTIVES: This study aimed to compare the interobserver Cohen κ on H&E staining and on H&E plus p16(INK4a) staining of all cervical biopsy specimens in a population-based screening program. METHODS: All the colposcopy-guided biopsies generated by the routine screening of 23,258 women aged 25 to 64 years were stained with H&E and H&E plus p16. Biopsy specimens were reviewed by six external experts. RESULTS: The four diagnoses were available in 441 cases. The interobserver κ values were 0.52 (95% confidence interval [CI], 0.45-0.58) and 0.48 (95% CI, 0.42-0.56) with H&E and H&E + p16, respectively, when using a five-group classification (normal, CIN 1, CIN 2, CIN 3, and cancer); adopting a two-group classification (≤CIN 1 and ≥CIN 2), the values were 0.75 (95% CI, 0.66-0.82) and 0.70 (95% CI, 0.61-0.79), respectively. CONCLUSIONS: The use of p16 on all cervical biopsy specimens in a screening program showed virtually no effect on reproducibility of the histologic diagnosis.

Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: a follow-up study.

P16-INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high-grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy-guided biopsy were included in the study; women surgically treated or having a CIN2-3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow-up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16-negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19-75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7-17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3-14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6-47.5). P16 overexpression is a good candidate for modulating follow-up intensity after a negative colposcopy but is limited by its low prospective sensitivity.

HPV testing is an efficient management choice for women with inadequate liquid-based cytology in cervical cancer screening.

This study compares colposcopy referrals of 2 management strategies: oncogenic human papillomavirus (HPV)-DNA testing (Hybrid Capture 2 assay, Qiagen, Germantown, MD) and repeat cytology. In the New Technology in Cervical Cancer Trial, 22,708 subjects were randomly assigned to undergo both HPV and liquid-based cytologic testing. Women aged 35 to 60 years old with unsatisfactory cytologic findings were directly referred for colposcopy if the HPV test result was positive, and were referred for repeat cytologic examination if the HPV test result was negative; women aged 25 to 35 years old were referred for repeat cytologic examination independent of HPV test results. A positive or a second unsatisfactory cytologic examination referred women for colposcopy. Five hundred sixty women had unsatisfactory cytologic findings. Colposcopy referral was not significant and slightly higher with HPV testing than repeat cytologic test (9.8% vs 6.8%, P = .11). When cytologic testing was repeated 36.8% were unavailable for follow-up and most of the colposcopies were performed in HPV-negative women. For unsatisfactory cytologic findings, HPV triage is a more logical and efficient management strategy than a repeat cytologic test.

Primary cutaneous adenoid cystic carcinoma of the upper lid: a case report and literature review.

To report on the diagnostic challenge of an adenoid cystic carcinoma arising from the eyelid. A 77-year-old male was referred to our center with a clinical diagnosis of upper eyelid chalazion for a lesion that had appeared 2 years before. A loss of cilia was observed over the cutaneous area of induration, but there was no reddening or ulceration. Incisional biopsy was performed and the specimen was submitted in formalin for histopathological examination. On light microscopy, the lesion was composed of basaloid epithelial and myoepithelial cells that were arranged in strands or nests and associated with cystic spaces that contained a deeply eosinophilic secretory substance and an Alcian blue-positive material, characteristic of adenoid cystic carcinoma. After histological diagnosis, tumor re-excision was performed to ensure adequacy of resection margins, as well as a sentinel lymph node procedure, resulting in complete excision of the malignant tumor. No recurrence was observed during the first 18 months after surgery. Adenoid cystic carcinoma is a rare and aggressive epithelial malignancy, which tends to grow slowly and should be considered in the differential diagnosis of eyelid tumors simulating chalazion.

Endoscopic ultrasound-guided fine needle aspiration with 22- and 25-gauge needles in solid pancreatic masses: a prospective comparative study with randomisation of needle sequence.

BACKGROUND: The difference in the diagnostic accuracy of 22- versus 25-gauge needles in EUS-FNA is not clear. AIMS: To compare the rates of technical success, diagnostic accuracy and complications of EUS-FNA performed with 22-gauge and 25-gauge needles on the same solid pancreatic mass. METHODS: All patients with solid pancreatic masses evaluated from September 2007 to December 2008 were enrolled and underwent EUS-FNA with both 22- and 25-gauge needles with randomisation of needle sequence. The accuracy of the EUS-FNA was determined by comparing the cytological results with the final surgical pathological diagnoses or with the results of a clinical follow-up. A cytological score with different qualitative parameters was created, and a comparison between these parameters was carried out for each needle. RESULTS: Fifty patients with 50 pancreatic masses were recruited. Technical success was 100% and no complications occurred. Diagnostic accuracy was 94% and 86% for the 25- and 22-gauge needles, respectively. Analysis of the cytological score showed a tendency towards the 25-gauge needle, although the difference was not statistically significant. CONCLUSIONS: EUS-FNA performed with 22- or 25-gauge needles had the same diagnostic accuracy. Our study results confirm a significant trend towards a better cytological diagnosis for the 25-gauge needle.

The reproducibility of CIN diagnoses among different pathologists: data from histology reviews from a multicenter randomized study.

The reproducibility of cervical histology diagnoses is critical for efficient screening and to evaluate the effectiveness of new technologies. The vast majority of cervical intraepithelial neoplasia (CIN) diagnoses reported in the New Technologies for Cervical Cancer study were blindly reviewed by 2 independent pathologists. Only H&E-stained slides were used for the review. The reviewers were asked to reclassify cases using the following categories: normal CIN 1, CIN 2, CIN 3, and squamous and glandular invasive cancer. We reviewed 1,003 cases. The interobserver agreement was 0.36 (95% confidence interval [CI], 0.32-0.40) with an unweighted kappa and 0.54 with a weighted kappa (95% CI, 0.50-0.58). The kappa values from dichotomous classifications with the threshold at CIN 2 were 0.69 (95% CI, 0.64-0.73) and 0.57 (95% CI, 0.51-0.63) with the threshold at CIN 3. The CIN 2 diagnosis had the lowest class-specific agreement, with fewer than 50% of cases confirmed by the panel members, which supports the fact that CIN 2 is not a well-defined stage in the pathogenesis of cervical neoplasia.

The risk of false-positive histology according to the reason for colposcopy referral in cervical cancer screening: a blind revision of all histologic lesions found in the NTCC trial.

All cervical intraepithelial neoplasia (CIN) diagnoses identified during the New Technologies for Cervical Cancer trial (ISRCTN81678807) were blindly reviewed by 2 pathologists. Original diagnoses based on colposcopy-guided biopsies were compared with those made by the reviewers who had access to all clinical histologic samples (including postsurgical). Cases downgraded from CIN 2+ by the reviewers were considered indicative of unnecessary treatments. The analyses are presented according to the molecular (high-risk human papillomavirus [HPV]) and/or cytologic diagnosis used to refer the women for colposcopy. We reviewed 812 CIN 1 and 364 CIN 2 + diagnoses. The specificity of colposcopy-guided biopsy was 98% and the sensitivity, 84%. The probability of unnecessary treatment was 27% for women with atypical squamous cells of undetermined significance cytologic findings and 8% for women with low-grade squamous intraepithelial lesion or worse, 10% for HPV+ and positive cytologic findings, and 16% for HPV+ alone. The positive predictive value of the first-level screening test was inversely associated with probability of a histologic false-positive result (P = .015). In screening, a low positive predictive value of the colposcopy-referring test may result in unnecessary treatments.