Metastatic Mucinous Carcinoma Research Articles

A Rare Case of Primary Ovarian Mucinous Carcinoma with Signet-Ring Cells and Literature Review.

The presence of signet-ring cells in the ovary is almost always associated with metastatic mucinous carcinomas known as Krukenberg tumors. Here we report a primary ovarian mucinous carcinoma with signet-ring cells, which is scarcely encountered, and a review of the literature to summarize the clinical and morphological features of these tumors. The patient was a 26-year-old female who had a large multicystic lesion in the right ovary. Macroscopic examination of the cyst revealed a 30 cm-sized multicystic lesion filled with mucinous material. The capsule was intact, and there was no surface involvement. Microscopically, a multicystic mucinous tumor with a predominantly borderline background and three well-demarcated nodules composed of signet ring cells without desmoplastic stroma were noted in the cyst wall. There was only one invasive focus seen. Immunohistochemically, conventional mucinous areas were diffusely positive for Keratin 7 and Keratin 20, and focally positive for PAX8, while negative for CDX2. Signet ring cells were positive for Keratin 20, CDX2, and Keratin 7, while negative for PAX8. In the systemic examinations, no potential primary site was found. The patient has not received any adjuvant treatment and has been followed for six years without disease, which is the longest follow-up time among previously reported cases. Signet ring cells can be present in primary ovarian mucinous carcinomas. The distinction from the more frequently seen metastatic carcinomas needs a complete evaluation of clinicopathological findings. Early-stage primary mucinous carcinomas having localized signet-ring cell nodules seem to have favorable prognosis without adjuvant treatment.

Multimodal diagnostic strategies and precision medicine in mucinous ovarian carcinoma: a comprehensive approach.

Mucinous ovarian carcinoma (MOC) represents a distinct entity within ovarian malignancies, characterized by diagnostic challenges due to its rarity and the potential overlap with other tumor types. The determination of tumor origin is important for precise postsurgical treatment. This article highlights the accurate diagnosis and management of MOC, including the use of imaging modalities, serological tumor markers, immunohistochemistry, and genomic analyses. Transabdominal and transvaginal ultrasonography, complemented by MRI and CT, plays a pivotal role in differentiating MOC from other mucinous tumors and in surgical planning, particularly for fertility preservation. Serological markers like CA19-9, CA-125, and CEA, though not definitive, provide valuable preoperative insights. Immunohistochemistry aids in distinguishing primary MOC from metastatic mucinous carcinomas, while genomic profiling offers the potential for precision medicine through the identification of specific molecular signatures and treatment susceptibilities. Despite advancements in diagnostic techniques, no single method conclusively differentiates between primary and metastatic tumors intraoperatively. The paper reviews the origins, diagnosis, and differential diagnosis of primary mucinous ovarian carcinoma highlights the need for a multimodal diagnostic approach and advocates for the inclusion of MOC patients in clinical trials for personalized therapies, recognizing the heterogeneity of the disease at the molecular level.

Mucin-producing tumors of the ovary——preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors

ObjectiveTo investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs).MethodsThis retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance.Results35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%.ConclusionsPatients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

CK7+/CK20+/CDX2+ mucinous carcinoma, arising in a mature cystic teratoma of ovary, presenting with disseminated metastasis and pseudomyxoma peritonei.

Mucinous carcinomas arising within an ovarian dermoid tumor are rare. Most of the cases reported in the literature show morphological features resembling an appendiceal mucinous neoplasm. They exhibit CK7-/CK20+ immunophenotype similar to carcinomas of the lower gastrointestinal tract. In this report, we have described a case of a well-differentiated mucinous carcinoma arising within a mature cystic teratoma. The mucinous carcinoma showed a spectrum of morphological patterns, including cystadenoma-like areas, proliferative/borderline areas, villous adenoma-like areas, and areas of invasive carcinoma. In addition, our case showed some unusual findings, namely, diffuse CK7 positivity, associated pseudomyxoma peritonei, and metastasis to lungs. These features were not demonstrated in any of the previously reported cases. Our case shows that the teratomatous mucinous neoplasm of the ovary may show CK7+/CK20+/CDX2 + immunoprofile making it immunohistochemically indistinguishable from a primary ovarian mucinous neoplasm or a metastatic mucinous carcinoma of the lower gastrointestinal tract.

Primary Primary Cutaneous Mucinous Carcinoma – A Case Report

Primary mucinous carcinoma of the skin is an uncommon malignancy of sweat gland origin. It is usually misdiagnosed clinically because of its benign appearance. On histological examination, it should be differentiated from metastatic mucinous carcinomas arising elsewhere in the body. We present a case of a 77-year-old male presenting with a swelling on the face, which was diagnosed clinically as a benign lesion, but on histological examination, it was diagnosed as mucinous carcinoma, and after thorough investigations, it was labelled as primary mucinous carcinoma of the skin.

Recurrent Primary Mucinous Carcinoma of the Skin

ABSTRACT Primary cutaneous mucinous carcinoma of the skin is an adenocarcinoma of eccrine glands. However, it may be locally aggressive and can metastasize to lymph nodes. Differential diagnosis especially from metastatic mucinous carcinomas of other organs such as breast, gastrointestinal tract, lung, prostate, and ovary may be difficult. Here we report a case of mucinous eccrine carcinoma with multiple recurrences even after surgical excision and radiotherapy. The patient also concomitantly diagnosed to have chronic lymphocytic leukemia after five years of diagnosis of mucinous carcinoma.

Bronchus-First Video-Assisted Left Lower Lobectomy for Metastatic Mucinous Carcinoma of the Lung

Bronchus-First Video-Assisted Left Lower Lobectomy for Metastatic Mucinous Carcinoma of the Lung

Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours

BackgroundThe vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC).MethodsImmunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases.ResultsAmong 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively.ConclusionClaudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.

Endocervical neoplasia: Pathologic updates in diagnosis and prognosis.

The diagnosis of adenocarcinoma of the uterine cervix can be challenging due to the varied histologic types different etiologies and their associated biologic behaviors and corresponding clinical management implications. To address these issues a new classification system has been developed and is introduced in the most recent edition of the WHO Classification of Female Genital Tumors. This system is based on morphology and the relationship with human papillomavirus (HPV). All the tumors are now classified into HPV-associated (HPVA) and HPV-independent (HPVI). In addition there are diagnostic pathology related advancements which are able to predict prognosis such as the incidence of lymph node metastasis and the tumor recurrence. These advances include cancer invasive patterns tumor nuclear grade and the status of necrotic tumor debris. This review will discuss endocervical adenocarcinomas (EAC) including their precursors in association with HPV. Instead of discussing each histologic type of ECA individually we group all EACs into four categories based on their dominant growth patterns including glandular papillary mucin producing and solid microscopic appearances. Differential diagnosis and diagnostic pitfalls are addressed in each category. The glandular growth pattern is the most common. In this category location is important to be considered for the differential. The mucin-producing group is comprised by HPVA and HPVI tumors and the differential diagnosis should include metastatic mucinous carcinomas. Serous carcinoma of the uterine cervix no longer exists; however the terminology serous-like adenocarcinoma has been designated to tumors with the serous morphology that are HPV positive. We include this tumor in the papillary architecture category. A solid growth pattern can be found in multiple histologic types of EAC and most of them behave aggressively. Histopathologic parameters with prognostic relevance are also briefly discussed.

A combination of immunohistochemical markers, MUC1, MUC5AC, PAX8 and growth pattern for characterization of mucinous neoplasm of the ovary

ObjectiveBecause mucinous carcinomas are rare tumors that affect several organ sites and are known to originate from different tissues, leading to frequent misdiagnoses, the objective was to characterize the differences...

Prognosis in primary mucinous ovarian carcinoma: focusing on the five pathological findings indicating metastatic mucinous carcinoma to the ovary.

ObjectivePathological features indicating metastatic mucinous carcinoma to the ovary (MMCO) have been rarely reported in primary mucinous ovarian carcinoma (PMOC). However, little is known about how often they are observed in PMOC and how they relate to patient prognosis. In this study, we investigated the pathological features indicating MMCO in a large cohort of PMOCs and analyzed their association with patient prognosis.MethodsWe reviewed surgically treated PMOC patients diagnosed at the Seoul National University Hospital from 1995 to 2019, according to the updated WHO classification, and investigated the presence of pathological features indicating MMCO.ResultsA total of 144 patients with PMOCs were included. The 5 pathological findings indicating MMCO, including an infiltrative invasive pattern, the absence of benign or borderline components, a smaller tumor size, the presence of signet ring cells and the presence of extracellular mucin were observed in PMOC (21.6%, 43.1%, 20.8%, 4.3% and 12.9%, respectively), and were significantly correlated with poor overall and progression-free survival rates in PMOC. The patient’s prognosis worsened as the extent of the infiltrative invasive pattern increased (p<0.001). In addition, the prognostic power was stronger when the 5 pathological factors were analyzed together (new grouping system) than when analyzed individually (p<0.001) and the new grouping system was identified as an independent prognostic factor regardless of FIGO stage.ConclusionFive pathological findings indicating MMCO in PMOC were significantly associated with poor prognosis in PMOC patients. Also, the new grouping system combining these findings was identified as an independent prognostic factor.

Claudin-18 Immunohistochemical Staining Facilitates the Identification of Metastatic Carcinoma of Gastric or Pancreatic Origin in Effusion Specimens.

Determining the primary origin of a malignant effusion remains a common challenge for cytopathologists. Although immunohistochemical (IHC) markers are available for most primary sites, ideal IHC markers for metastatic gastric adenocarcinoma and pancreatic ductal adenocarcinoma are lacking, and related interpretation is often hindered by mesothelial cells. We recently revealed that claudin-18 IHC staining is useful for identifying the stomach and pancreas as the primary sites of metastatic adenocarcinoma. Thus, we assessed the use of claudin-18 IHC staining in 111 cell blocks obtained from various metastatic cancers and specimens negative for malignancy. Positive membranous claudin-18 staining was noted in all 10 (100%) metastatic pancreatic ductal adenocarcinomas, 9 (90%) of 10 gastric adenocarcinomas, and 1 (9%) of 11 nonmucinous lung adenocarcinomas. The cases of metastatic mucinous carcinomas of lung origin (1 case) and ovarian origin (1 case) were also positive for claudin-18. The other remaining 89 cases showed variable cytoplasmic staining on some cells (73 cases) or complete absence of staining (16 cases). After normalization to the tumor frequency, the sensitivity and specificity for identifying the stomach or pancreas as primary tumor sites in ascites were 95% (confidence interval: 0.83-0.99) and 99% (confidence interval: 0.94-1), respectively. In conclusion, membranous claudin-18 staining is a useful marker for metastatic gastric adenocarcinoma and pancreatic ductal adenocarcinoma in effusion specimens.

English

Primary cutaneous mucinous carcinoma (PCMC) also known as primary mucinous carcinoma of the skin (PMCS) or primary mucinous eccrine carcinoma (PMEC) is a rare malignant adnexal tumour of eccrine origin. Many visceral mucinous carcinomas especially of the breast and gastrointestinal tract can metastasize to the skin mimicking PCMC. Hence it is very important to rule out metastatic mucinous carcinomas before making a diagnosis of PCMC. Usually, PCMC presents as a slowgrowing tumour of considerably smaller size compared to our case. The large size and shorter duration are the key features of this case report. Here we report an unusually large-sized rare malignant tumour of skin appendage. Our patient was a 54-year-old lady who presented with progressive swelling of one year duration in the right frontoparietal area. Ultrasonography showed an ill-defined lesion in the subcutaneous plane with multiple cystic spaces within it. No bone involvement was noted. The excised lesion measured 13 x 7 x 2 cms and was diagnosed as primary cutaneous mucinous carcinoma on histopathological examination. The possibility of cutaneous secondaries from elsewhere was ruled out by detailed clinical and radiological investigations. The case is reported considering the unusually bigger size and shorter duration of this rare entity.

Limitations of Immunohistochemistry in Diagnosis of a Primary Mucinous Carcinoma of the Skin and Its Metastasis

We describe the case of a 67-year-old female patient who presented with an unclear swelling on the right supraclavicular neck, two years after resection of a mucinous carcinoma on the right mastoid. Two pathological reports from separate universities diagnosed the primary mastoid skin lesion as a metastatic adenocarcinoma. Strikingly, GATA binding protein 3 (GATA3) and mammaglobin, both immunomarkers found in breast cancer, were positive. An urgent search for the primary tumor most likely in the breast was commenced. However, as no other primary tumor could be detected at that time, a Primary Mucinous Carcinoma of the Skin (PMCS) was also debated. Two years later neck node enlargement was suspicious for lymph node metastasis during ultrasound examination and conservative neck dissection was performed. Immunohistochemistry revealed again GATA 3, Mammaglobin, estrogen, and progesterone receptor positive tissue. Using a variety of other markers, we were unable to detect neither significant morphological nor immunohistochemical characteristics that distinguished the lesion from a mucinous carcinoma of mammary origin. Following a detailed review of the clinical context, we concluded the lesion to be consistent with a late metastasis of a PMCS. This report demonstrates the limitations of currently used histopathological and immunohistochemical differentiation in metastatic mucinous carcinoma.

A Rare Case of Metastatic Mucinous Breast Carcinoma as a First Presentation of Colon Cancer in a Male Patient: Case Report and Review of the Literature

The majority of breast tumors are primary; however metastatic tumor to the breast from extramammary sites has an incidence of 0.5 to 3% and can be misinterpreted clinically as a primary breast tumor. We report a case of metastatic mucinous breast carcinoma as a first presentation from colon cancer in a male patient who hasn’t had any bowel symptoms. The immunohistochemical study helped in suspecting the diagnosis, which was then confirmed by CT scan abdomen and pelvis and endoscopic biopsy of the colonic lesion. Management of such patients usually by palliative chemotherapy due to the aggressive nature of the disease however, surgical intervention may be indicated in symptomatic patient or risk of tumor ulceration as in our patient.

Mucinous Cancer of the Ovary: Overview and Current Status.

Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease.

Response to “Novel” nomogram and algorithm do not aid in the distinction of primary vs. metastatic mucinous carcinoma of ovary: letter to the Editor

Response to “Novel” nomogram and algorithm do not aid in the distinction of primary vs. metastatic mucinous carcinoma of ovary: letter to the Editor

Primary Cutaneous Mucinous Carcinoma with Extramammary Paget's Disease: Eccrine or Apocrine?

Primary cutaneous mucinous carcinoma (PCMC) is an uncommon tumor of the sweat gland origin. The occurrence of PCMC is mostly in middle-aged and older patients, with a slight male predominance. Most cases of PCMC arise on the head, with a preference for eyelids. The histogenesis of PCMC, whether eccrine or apocrine, remains controversial. We report a rare case of PCMC with secondary extramammary Paget’s disease in the groin of a 75-year-old man, which favored an apocrine origin. Furthermore, based on a review of the literature, we provide several histologic clues that can be used to differentiate PCMC from metastatic mucinous carcinoma.

The utility of KRAS mutation analysis in differentiating a lung primary mucinous carcinoma from a metastatic colorectal mucinous carcinoma

A 58-year old male has a past medical history of a rectal low-grade mucinous adenocarcinoma with a KRAS codon 12/13 mutation (GGT&gt;GAT), for which he received neoadjuvant chemotherapy and radiation. Five months after diagnosis, the patient underwent a low anterior resection showing persistent tumor with the pathological staging being (ypT3, ypN0, ypMx). Six months after surgery, follow-up PET scan showed two right upper lung nodules measuring 1.0 and 1.8 cm. Subsequent video-assisted thoracic surgery with a lung wedge resection revealed two tumors: a mucinous adenocarcinoma and an acinar-predominant adenocarcinoma. The mucinous adenocarcinoma showed similar cytologic features as the rectal tumor; however, it showed more of a lepidic pattern. The immunohictochemical profile of the lung mucinous adenocarcinoma was positive CK7 (cytoplasmic), negative CK20, TTF1, napsin-A, and CDX2. KRAS codon 12/13 analysis also showed a mutation in the lung, however it was different compared to the previous rectal tumor and showed a GGT&gt;AGT mutation. The acinar adenocarcinoma had a wild-type KRAS. In this case, we favored a primary lung mucinous carcinoma over a metastasis from the rectum based on the lepidic morphology, CK20 negativity and differing KRAS codon 12 mutations. A year after the resection of the lung adenocarcinomas, the patient presented with dyspnea and abnormal liver functions. Abdominal US and MRI revealed multiple liver lesions (up to 1.9 cm). Core liver biopsies showed a poorly-differentiated mucinous adenocarcinoma with positive CK7 (cytoplasmic) and negative CK20, TTF-1, napsin-A, CDX2 and HSA. KRAS codon 12/13 analysis also showed a mutation GGT&gt;AGT, similar to that of the lung mucinous adenocarcinoma. The immunohistochemical profile and the KRAS mutation sequence of the hepatic tumor suggests a metastasis from the lung primary and corroborates the earlier premise that the lung tumor is distinct from the rectal one. In conclusion, in the unusual circumstance of a lung mucinous adenocarcinoma in a patient with established gastrointestinal mucinous primary, KRAS mutation analysis sequencing could help distinguish whether the lung mucinous is a primary tumor or metastasis from colorectal origin.