Anti-synthetase and myelodysplastic syndromes with deep morphea: an example of shared immunopathogenesis? A case-based review.

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient.

Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract Mimicking Crohn's Disease.

Indolent clonal T-cell lymphoproliferative disorder (iCTLD-GI)/indolent T-cell lymphoma of the gastrointestinal tract (iTLP-GI) poses diagnostic challenges, and despite its rarity, accurate diagnosis is crucial for appropriate management. We report the case of 34-year-old female with a 19-year history of gastrointestinal symptoms suggestive of inflammatory bowel disease (IBD). Subsequent evaluation revealed iCTLD-GI/iTLP-GI with extensive Crohn's disease-like morphological alterations, previously unreported. These macroscopic and microscopic aspects underscore the need for a comprehensive evaluation to avoid misdiagnosis with IBD. Additionally, molecular studies have identified potential therapeutic targets, highlighting the evolving management strategies. This case underscores the diagnostic complexity of iCTLD-GI/iTLP-GI, especially when the condition mimicks IBD such as Crohn's disease.

Sclerosing Angiomatoid Nodular Transformation of the Spleen in a Patient With Granulomatosis With Polyangiitis.

We present an intriguing case involving a rare occurrence of sclerosing angiomatoid nodular transformation (SANT) in a 57-year-old woman with a history of granulomatosis with polyangiitis (GPA). Despite the extensive literature on SANT, its pathogenesis remains elusive. The patient, diagnosed with serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA)-positive GPA seven years earlier, exhibited a splenic lesion during imaging, leading to laparoscopic splenectomy due to severe abdominal pain. Microscopic analysis unveiled nodular structures with vascular elements surrounded by fibrosclerotic stroma and chronic inflammatory cells. This case raises questions about the interplay between SANT, GPA activity, and vascular damage. Hypotheses regarding SANT's origin, including its potential association with organized hematoma or alterations in splenic blood flow, are discussed. The uniqueness of this case lies in the coexistence of PR3-ANCA-positive GPA and SANT, suggesting a potential link between GPA activity, vascular damage, and SANT development. While causality remains uncertain, this report marks the first documented case of a patient with PR3-ANCA-positive GPA developing SANT. The findings prompt reflection on a potential common pathophysiological mechanism and underscore the importance of considering SANT in cases of splenic lesions associated with conditions causing alterations in splenic blood flow. This contribution serves as a valuable addition to the existing knowledge, urging further research and consideration of SANT in diagnostic scenarios involving splenic abnormalities.

Is Iron Overload Associated with Worse Outcomes in Patients with Chronic Liver Disease Undergoing Liver Transplantation?

ABSTRACT Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 person-months; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Is iron overload associated with worse outcomes in patients with chronic liver disease undergoing liver transplantation?

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Increased synthesis and intestinal expression of IL-39 in patients with inflammatory bowel disease.

IL-39 (Interleukin-39) is a heterodimeric cytokine composed of IL-23p19 and EBI3 (Epstein-Barr virus-induced gene 3) subunits. Despite the evidence that correlates the role of IL-39 in regulating inflammation, its expression in the intestinal microenvironment of IBD (inflammatory bowel disease) patients is still unknown. Thus, this work was focused on characterizing relative mRNA (messenger RNA) IL-39 expression and intestinal synthesis in IBD patients. This study includes 37 patients diagnosed with ulcerative colitis (UC), 15 with Chron's disease (CD), and 22 controls. Gene expression of IL-39 subunits (IL-23p19/EBI3) was measured by RT-PCR (real time polymerase chain reaction). Intestinal synthesis was evaluated by immunohistochemistry and serum levels by ELISA. Statistical analysis was done using Prism GraphPad V6. Relative mRNA IL-39 expression was increased in patients with active UC and active CD compared to the remission UC, remission CD, and control group. High levels of relative mRNA expression of IL-39 (IL-23p19 subunit) were associated with histological activity. IHQ analysis showed increased IL-39 production in mucosa, submucosa, muscular, and serosa layer of patients with active disease. IL-39 serum production was increased in patients with UC. IL-39 gene's upregulation was found in patients with active IBD and was associated with severe histological activity in UC. This is the first report regarding the role of IL-39 in patients with IBD. The findings suggest that IL-39 might play a role as an inflammatory mediator in active IBD and could be considered a new alternative in treating this condition.

Combined loss of CDH1 and downstream regulatory sequences drive early-onset diffuse gastric cancer and increase penetrance of hereditary diffuse gastric cancer.

BACKGROUND: Germline CDH1 pathogenic or likely pathogenic variants cause hereditary diffuse gastric cancer (HDGC). Once a genetic cause is identified, stomachs' and breasts' surveillance and/or prophylactic surgery is offered to asymptomatic CDH1 carriers, which is life-saving. Herein, we characterized an inherited mechanism responsible for extremely early-onset gastric cancer and atypical HDGC high penetrance. METHODS: Whole-exome sequencing (WES) re-analysis was performed in an unsolved HDGC family. Accessible chromatin and CDH1 promoter interactors were evaluated in normal stomach by ATAC-seq and 4C-seq, and functional analysis was performed using CRISPR-Cas9, RNA-seq and pathway analysis. RESULTS: We identified a germline heterozygous 23 Kb CDH1-TANGO6 deletion in a family with eight diffuse gastric cancers, six before age 30. Atypical HDGC high penetrance and young cancer-onset argued towards a role for the deleted region downstream of CDH1, which we proved to present accessible chromatin, and CDH1 promoter interactors in normal stomach. CRISPR-Cas9 edited cells mimicking the CDH1-TANGO6 deletion display the strongest CDH1 mRNA downregulation, more impacted adhesion-associated, type-I interferon immune-associated and oncogenic signalling pathways, compared to wild-type or CDH1-deleted cells. This finding solved an 18-year family odyssey and engaged carrier family members in a cancer prevention pathway of care. CONCLUSION: In this work, we demonstrated that regulatory elements lying down-stream of CDH1 are part of a chromatin network that control CDH1 expression and influence cell transcriptome and associated signalling pathways, likely explaining high disease penetrance and very young cancer-onset. This study highlights the importance of incorporating scientific-technological updates and clinical guidelines in routine diagnosis, given their impact in timely genetic diagnosis and disease prevention.

Acne Necrotica in a Woman With Systemic Lupus Erythematosus and Systemic Sclerosis.

We report the case of a 25-year-old woman who presented to the outpatient dermatology clinic with a history of systemic lupus erythematosus, systemic sclerosis, and primary hypothyroidism. She complained of a one-year history of cutaneous lesions that were pruriginous and evolved into crusts and weeks later resolved with varioliform scarring. Clinicopathological correlation established a diagnosis of acne necrotica varioliformis. This report highlights the clues and pitfalls in its diagnosis and reviews associated systemic diseases.

AKAP12/Gravin is over-expressed in patients with ulcerative colitis.

The gene of A-kinase anchor protein 12 (AKAP12) regulates cell cycle progression, cell motility, and morphology through its multiple scaffolding domains. However, the role of AKAP12 expression in ulcerative colitis (UC) patients has not been yet described. The aim of the study was to describe the gene and protein of AKAP12 expression in patients with UC and its association regarding the disease severity. We included a total of 40 patients with confirmed diagnosis of UC and 25 controls without endoscopic evidence of colitis or neoplasia. The relative quantification of the gene expression was performed by real-time PCR for AKAP12. Kruskal-Wallis was used to test differences among groups, and Spearman correlation to assess the relationship between AKAP12 gene and clinical outcomes. The extent of disease was evaluated using total colonoscopy, and biopsies were taken from rectum segments. The AKAP12 gene expression was increased in colonic mucosa from patients with active UC when compared with UC remission and control group. The overexpression of AKAP12 in patients with UC was associated with the presence of extensive colitis (p = 0.04, RM = 12, IC = 1.29-186.37). AKAP12/CD16 double positive cells were higher in submucosa (p = 0.04), muscular (p < 0.001), and cells from serosa (p < 0.001) in patients affected by UC in comparison to controls. The overexpression of AKAP12 was associated with the extent of disease. This is the first report about the role of AKAP12 in patients with UC suggesting that this gene and its protein could be involved in the modulation of the disease.

Intestinal production of secreted protein acidic and rich in cysteine (SPARC) in patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the intestine. The genetics factors play an important role in the pathogenesis of UC. SPARC exacerbates colonic inflammatory symptoms in dextran sodium sulphate-induced murine colitis. The aim of the study was to measure the gene expression and intestinal production of SPARC in patients with UC and controls as well as, to determine its correlation with histological activity. METHODS: We included 40 patients with confirmed diagnosis of UC, and 20 controls without endoscopic evidence of any type of colitis or neoplasia. The relative quantification of the gene expression was performed by real time PCR. GAPDH was used as housekeeping gene for normalization purposes and quality controls. Protein expression was determined by immunohistochemistry. RESULTS: The gene expression of SPARC was increased in patients with active UC vs in remission UC and vs. controls (P = 0.005). There was no significant difference between patients with remission UC and controls. The overexpression of SPARC in patients with active UC correlated significantly with mild histological activity (P = 0.06, OR = 7.77, IC = 0.77-77.9) moderate (P = 0.06, OR = 8.1, IC 95%=0.79-82.73), and severe (P = 0.03, OR = 6.5, IC 95%=1.09-38.6). Double positive SPARC+/CD16+ cells were localized mainly in submucosa, muscular layer, and adventitia, and in perivascular inflammatory infiltrates in patients with active UC. CONCLUSION: The gene and protein expression of SPARC is increased in active UC. SPARC could be a marker of intestinal inflammation and its expression correlates with histological activity.

Prevalence and clinical characteristics of alpha-1 antitrypsin deficiency in liver explants in a Mexican cohort.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a risk factor for liver disease. PASD-positive inclusions have been found unexpectedly in approximately 10% of liver explants in patients with no previous diagnosis of AATD, particularly, in patients with non-alcoholic steatohepatitis (NASH), supporting a synergistic mechanism of liver injury between AATD and environmental factors. We aimed to determine the clinical characteristics of mestizo patients in which AATD was diagnosed before or after liver transplantation. METHODS: Liver explants of patients with cryptogenic, alcoholic, and NAFLD/NASH cirrhosis undergoing orthotopic liver transplantation (OLT) were included. Liver histopathology was assessed by two expert pathologists. Hematoxylin and eosin staining, PASD staining, and confirmatory AAT immunohistochemistry were performed. In explants with positive histopathology, genotyping for SERPINA1 was performed. RESULTS: A total of 180 liver transplants were performed during the study period. Of these, 44 patients with cryptogenic cirrhosis, NASH, and alcoholic cirrhosis were included. Of these patients, two liver explants (4.5%) had PASD-positive inclusions stain and confirmatory immunochemistry. During the period evaluated, another two patients with a diagnosis of AATD before the OLT were also included. The four patients had overweight or obesity, three had type 2 diabetes mellitus, and two developed liver steatosis after the OLT. CONCLUSION: AATD was found to be an infrequent finding in patients with cryptogenic, NASH/NAFLD, and alcoholic cirrhosis in our population. However, it is important to consider this entity as it may represent an additional factor in the appearance and progression of liver fibrosis in patients with metabolic syndrome.

Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross-sectional study.

It has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT-PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P = .045), remission (r)CD group (P = .0009) and controls (P < .0001). We detected differences between rUC and aCD (P = .004), rCD (P < .0001) or control group (P < .0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P = .0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P = .0001). MMP10 gene expression is associated with inflammation in UC patients (P = .0001, r2  = .585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process.

Expression of TOB/BTG family members in patients with inflammatory bowel disease.

In recent years, the role of anti-proliferative TOB proteins in the regulation of immune response by inhibiting T cell activation has been demonstrated. Nevertheless, no previous studies have explored their expression in patients with IBD. The aim of the study was to characterize the gene and protein expression of the TOB/BTG family in intestinal tissue of patients with IBD. This is an observational and cross-sectional study that included 63 IBD patients. Gene expression of TOB/BTG family was measured by RT-PCR. Protein expression of TOB/CD16 and BTG/Ki-67 was evaluated by immunohistochemistry. TOB/BTG family mRNAs were detected and quantitated by RT-qPCR in rectal and ileum biopsies from UC patients and CD patients, respectively, and non-inflammatory control tissues. Results showed that TOB1 and BTG1 gene expression was decreased in the colonic mucosa from patients with UC compared with the control group. The TOB2 and BTG2 genes were over-expressed in the colonic mucosa of patients with UC in remission compared with the active UC and control group. The high TOB2 gene expression was associated with histological remission (P = .01). TOB1/CD16, TOB2/CD16, BTG1/Ki-67, BTG2/Ki-67 and BTG4/Ki-67 single and double positive cells were mostly NK, macrophages, epithelial cells, connective tissue cells and perivascular inflammatory infiltrates in tissues from patients with UC and CD. This is the first depiction of the TOB/BTG family gene and protein expression in rectal and ileum tissues by a CD16+ subpopulation in IBD.

Histopathologic Parameters at Diagnosis as Early Predictors of Histologic Remission along the Course of Ulcerative Colitis.

BACKGROUND: Currently, the treatment goal in ulcerative colitis (UC) is to achieve clinical and endoscopic remission; nevertheless, histologic remission is a potential new treatment goal since it is associated with favorable long-term clinical outcome lower rates of hospitalization, complications, and colectomies. AIM: Evaluate clinical and histopathologic characteristics at diagnosis as potential predictors of histologic remission in patients with ulcerative colitis. METHODS: This is a retrospective cohort study from 2007 to 2014, including 260 patients. Clinical and demographic information and Mayo endoscopic and Riley histologic grade were obtained accordingly with the follow-up. Histological evaluation was made for all 260 patients; fifty-six patients with histologic remission at the follow-up underwent separate evaluation of mucosal biopsy at the moment of diagnosis. Univariate and multivariate analyses were applied to data from these 56 patients to identify histologic features at diagnosis associated with histologic remission during follow-up. The odds ratio (OR) was determined as a measure for the strength of association. A P value of less than 0.05 was taken as a level of significance. RESULTS: The frequency of histologic remission according to the Riley index in our study group was 21.5%. Factors associated with histologic remission were treatment with steroids (P = 0.01, OR = 0.38, CI 95% = 0.16-0.90), reduced mucin production (P = 0.02, OR = 0.23, CI 95% = 0.06-0.86), and less than 10 eosinophils per high power field (P = 0.001, OR = 6.66, CI 95% = 2.03-21.84). CONCLUSION: Factors that impair histologic remission in patients with ulcerative colitis were treatment with steroids and reduced mucin production; meanwhile, less than 10 eosinophils per high power showed a predictive value for histologic remission.

Disorders of Sex Development and Malignant Germ Cell Tumors.

A woman, aged 44 years, presented at the general oncology outpatient clinic with bloating, abdominal pain, and significant unintended weight loss. Her past medical history included a bilateral inguinal hernia surgical repair at age 6, and primary amenorrhea since age 15. The patient never underwent additional studies to identify the cause of the primary amenorrhea.

Hepatic manifestations in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-organic autoimmune disease with a wide variety of clinical manifestations. However, hepatic dysfunction is not included in the diagnostic criteria for the disease and has not been recognized properly. The spectrum of hepatic involvement described in these patients ranges from abnormalities in liver function tests (LFTs) to fulminant hepatic failure. Usually, abnormalities in LFTs are only mild and transient, have a hepatocellular pattern and are not related to SLE but rather are mostly drug related. The most frequent finding on liver biopsy is steatosis (non-alcoholic fatty liver disease). Patients do not frequently progress to advanced chronic liver disease, and their outcome is favourable. Those who develop cirrhosis have traditional risk factors, such as other non-SLE-related conditions. In this work, we aim to review hepatic manifestations in patients with SLE, as well as the diagnostic and therapeutic approaches used for different liver diseases in these patients.

TRPV Subfamily (TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) Gene and Protein Expression in Patients with Ulcerative Colitis.

INTRODUCTION: TRPVs are a group of receptors with a channel activity predominantly permeable to Ca2+. This subfamily is involved in the development of gastrointestinal diseases such as ulcerative colitis (UC). The aim of the study was to characterize the gene and protein expression of the TRPV subfamily in UC patients and controls. METHODS: We determined by quantitative PCR the gene expression of TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 in 45 UC patients (29 active UC and 16 remission UC) and 26 noninflamed controls. Protein expression was evaluated in 5 µm thick sections of formalin-fixed, paraffin-embedded tissue from 5 customized severe active UC patients and 5 control surgical specimens. RESULTS: TRPV2 gene expression was increased in the control group compared with active UC and remission patients (P = 0.002 and P = 0.05, respectively). TRPV3 gene expression was significantly higher in controls than in active UC patients (P = 0.002). The gene expression of TRPV4 was significantly higher in colonic tissue from patients with remission UC compared with active UC patients (P = 0.05) and controls (P = 0.005). TRPV5 had significantly higher mRNA levels in a control group compared with active UC patients (P = 0.02). The gene expression of TRPV6 was significantly higher in the colonic tissue from patients with active UC compared with the control group (P = 0.05). The protein expression of TRPV2 was upregulated in the mucosa and submucosa from the controls compared with the UC patients (P ≤ 0.003). The protein expression of TRPV3 and TRPV4 was upregulated in all intestinal layers from the controls compared with the UC patients (P < 0.001). TRPV5 was upregulated in the submucosa and serosa from the controls vs. UC patients (P < 0.001). TRPV6 was upregulated in all intestinal layers from the UC patients vs. controls (P ≤ 0.001). CONCLUSION: The TRPV subfamily clearly showed a differential expression in the UC patients compared with the controls, suggesting their role in the pathophysiology of UC.

Atrophic and Microcystic Limited Prostatic Adenocarcinomas.

Atrophic carcinoma and microcystic carcinoma have previously been classified as variants of conventional acinar adenocarcinoma. In this article, we studied 4 cases of atrophic carcinoma and 4 cases of limited microcystic carcinoma. We found an incidence of 0.8% in 250 needle prostatic biopsies and 1.3% of atrophic carcinoma in 150 radical prostatectomies. Microcystic carcinomas were found in 3 prostatectomies (1.2%) and in 1 needle biopsy (0.67%). The useful histological criteria for atrophic carcinoma included the irregular disposition of the glands, infiltrative pattern, "rigid" luminal borders, and intraluminal secretions. Cytological changes included scant cytoplasm, nucleomegaly, hyperchromatic nuclei, and visible nucleoli. The glands of the microcystic carcinoma differ from the benign glands because the malignant ones show a markedly greater dilatation and exhibit rigidity of glandular lumens. In some cases of microcystic carcinoma, the nuclei were flattened, small, and hyperchromatic; therefore, they can be difficult to recognize as malignant.