Differential Diagnosis Of Metastatic Carcinoma Research Articles

The cytologic diagnosis of mesothelioma: are we there yet?

Mesothelioma is a rare but highly aggressive malignancy with poor prognosis that frequently present with recurrent effusions. Establishing the diagnosis by cytology can lead to early diagnosis and treatment and consequently improve prognosis. This review examines the cytological diagnosis of mesothelioma in the context of its historical and morphologic evolution and provides an update of the current reporting systems. Clues to identify the mesothelial and malignant nature of the sample are detailed as well as the supporting ancillary tests. Cytologically, the samples are overwhelmingly cellular and malignancy is recognized by both architectural and cytological atypia. Numerous variably sized clusters and enlarged cells are easily identified, some with papillary architecture and collagen cores. Recognizing the mesothelial nature of the cells and supportive immunostains are essential to rule out the differential diagnosis of metastatic carcinomas and reactive mesothelium. Current ancillary tests such as homozygous deletion of CDKN2A, loss of BRCA1-associated protein, and methylthioadenosine phosphorylase expression can provide further support of malignancy. At this time with the aid of current ancillary tests and in the hands of cytopathologists with adequate experience with the interpretation of effusions, the diagnosis of mesothelioma can be established with accuracy in most cases.

Immunohistochemical Markers for Distinguishing Metastatic Breast Carcinoma from Other Common Malignancies: Update and Revisit.

Due to the high prevalence of breast cancer in the female, a metastasis from primary breast cancer is usually considered in the differential diagnosis of metastatic carcinoma in the female patient, even for those without a history of breast cancer, as some breast cancers are first diagnosed as metastases. Immunohistochemical analysis for breast cancer markers is the most common way to determine breast cancer origin besides clinical history and histology. In this review, we (1) summarize the commonly used and the newly identified breast cancer markers, including GCDFP-15, mammaglobin, GATA3, SOX10, and TRPS1; (2) point out the strengths and weaknesses of using these markers for breast cancers with luminal/epithelial or basal/myoepithelial differentiation; and (3) recommend diagnostic panels to differentiate breast carcinoma from carcinoma with similar morphology of other origins.

Malignant Melanoma Presenting as Multiple Lytic Bone Lesions Masquerading as Carcinoma of Unknown Primary on Clinical and Histopathological Examination

Malignant melanoma presenting as multiple lytic bone lesions masquerading as carcinoma of unknown primary on clinical and histopathological examination. Malignant melanomas are aggressive tumours with frequent metastasis to lymph nodes and viscera. However, patients presenting with osseous metastasis of melanoma with no known primary source is relatively rare. The terminology “metastases of unknown origin” is used when the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and imaging studies. Metastatic melanoma can have varied presentations. Herein, this is a case report of a 63-year-old female who presented with swelling in the occipital region of eight-month duration. Examination showed bony hard fixed swellings in the occipital and mastoid regions. Computerised Tomography scan (CT scan) showed lytic bone destruction in the occipital and mastoid part of right temporal bone, associated with soft tissue mass. With the differential diagnosis of metastatic carcinoma and myeloma, biopsy was taken which showed infiltrating neoplasm with plasmacytoid cells in cords and in vague nests surrounded by fibrosis. The neoplastic cells were Cytokeratin negative, Cluster of Differentiation (CD) 138 negative and showed patchy nuclear positivity for S100. On subsequent examination, the neoplastic cells showed diffuse strong positivity for HMB 45 (Human Melanoma Black) and patchy moderate positivity for Melan A confirming the diagnosis of malignant melanoma. Primary lesion could not be detected even after a detailed past medical and surgical history, physical examination and radiological investigations. The main causes of skull lytic lesions in adults are metastatic carcinoma and plasma cell myeloma. Possibility of metastatic melanoma should also be considered in cases of skull bone lesions as melanomas could exhibit varying cellular morphology mimicking carcinoma, sarcoma or haematolymphoid neoplasms.

Coexpress of GATA-3 and ER in Anorectal and Head and Neck Squamous Cell Carcinoma Mimicking Metastatic Breast Cancer.

GATA binding protein 3 (GATA-3) is a sensitive marker for breast and urothelial carcinomas. In combination with the estrogen receptor (ER), it is often used for differential diagnosis of metastatic carcinomas of breast origin. In this study, we sought to characterize GATA-3 and ER expression in squamous cell carcinoma (SqCC) of various origins to compare with breast carcinoma. Sixty-four SqCC of anorectum (35), head and neck (15), lung (11), and breast (3) as well as urothelial carcinoma (31) were included. In anorectal and head and neck SqCC, GATA-3, and ER was observed in 23/50 (46.0%) and 18/50 (36.0%) of the cases, respectively. The expression of GATA-3 and ER were present in both male and female patients without significant sex predominance. In 2 metastatic SqCC, the GATA-3 and ER expressed similar immunoreactivity compatible with their anorectal primary. Progesterone receptor was only expressed in 2 anorectal SqCC and none of head and neck SqCC or urothelial carcinomas. None of the lung SqCC expressed GATA-3 or ER (0/11). p16 was expressed in the majority of head and neck (6/12) and anorectal SqCC (26/27). Our study demonstrated that the combination of GATA-3 and ER positivity is not entirely specific for breast carcinomas, since both stains are expressed in SqCC from anorectal and head and neck origins. Clinical workup for metastatic carcinoma of suspicious breast origin should be cognizant of other tumors with a similar immunohistochemical profile (ie, SqCC).

Pathologic differential diagnosis of metastatic carcinoma in the liver.

The liver is one of the most common sites to which malignancies preferentially metastasize. Although a substantial number of liver malignancies are primary tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the metastasis of carcinomas to the liver is relatively common and frequently encountered in clinical settings. Representative carcinomas that frequently metastasize to the liver include colorectal carcinoma, breast carcinoma, neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic confirmation of suspected metastatic lesions in the liver is generally achieved through a histopathologic examination of biopsy tissues. Although morphology is the most important feature for a pathologic differential diagnosis of metastatic carcinomas, immunohistochemical studies facilitate the differentiation of metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin, etc.). Here, we provide a brief review about the pathologic differential diagnosis of major metastatic carcinomas in the liver.

Follicular Carcinoma of Thyroid with the First Presentation as Vertebral Column Metastasis: A Case-report

Follicular carcinoma of thyroid is the second most common type of thyroid cancer that its incidence has increased in recent years. Herein, the study reported a 64-year male case of follicular carcinoma of thyroid that his first presentation was vertebral column metastasis. His chief complaint was back pain. In the past medical history, the patient had hypothyroidism and was opium inhalation addict since 15 years ago. Thoraco-lumbar magnetic resonance imaging (MRI) demonstrated spinal tumor of T10. The pathology report showed metastatic follicular carcinoma of thyroid with Thyroid transcription factor-1 (TTF-1), Thyroglobulin (TG), and Cytokeratin-7 (CK-7) positivity. Then thyroidectomy confirmed the diagnosis. In conclusion, follicular carcinoma of thyroid may be presented with spinal column metastasis. Pathologist should consider this diagnosis in the differential diagnosis of metastatic carcinoma in vertebral column and use Thyroglobulin with TTF-1 in immunohistochemistry panel for definite diagnosis and identification of origin.

Choroid plexus carcinoma in an adult

Choroid plexus carcinoma is a very rare tumor in adults. Here we report a rare case of choroid plexus carcinoma in an adult patient. A 24-year-old male presented with a right temporal intraventricular tumor with a cystic component also extending up to the cortex. Histological examination revealed complex papillary structures and glandular spaces showing stratification and multilayering of cells with nuclear crowding and numerous mitotic figures and large areas of necrosis. The patient went through a complete search for a possible primary keeping in mind the differential diagnosis of metastatic carcinoma that is more common in adults but there was no evidence of any other tumor. Finally a diagnosis of choroid plexus carcinoma was rendered. Immunohistochemical analysis for p53 protein showed positivity. Choroid plexus carcinoma is exceptionally rare in adults but cases do occur.

Hemangioendothelioma of soft tissue: Cytological dilemma in two cases at unusual sites

Hemangioendothelioma is a rare vascular tumor of intermediate malignancy. Cytologically, it can simulate a non-vascular malignant tumor. We report two cases of this tumor, which were misdiagnosed at cytology. In the first case, a 27-year-old man presented with an anterior abdominal wall tumor. Fine needle aspiration cytology (FNAC) of the tumor showed polygonal cells with vacuolated cytoplasm in clusters having moderate nuclear atypia in a background of necrosis. A diagnosis of metastatic carcinoma was made. The histological examination showed features of epithelioid hemangioendothelioma. In the second case, a 13-year-old female child presented with unilateral enlargement of the right tonsil. At ultrasound-guided FNAC, a diagnosis of, ‘small round cell tumor, could be consistent with alveolar rhabdomyosarcoma,’ was made. The histological examination showed features of papillary intralymphatic angioendothelioma (Dabska's tumor). We conclude that epithelioid hemangioendothelioma should be considered in the differential diagnosis of metastatic carcinoma and small round cell tumor even at unusual sites.

Superficially invasive transitional cell carcinoma of the bladder associated with distant cutaneous metastases

Cutaneous metastases from transitional cell carcinoma of the bladder are rare and most often associated with a deeply invasive primary tumor. This case report describes a 69-year-old male with previously resected superficially invasive primary transitional cell carcinoma of the bladder who presented with distant cutaneous and central nervous system metastases associated with recurrent bladder cancer. In addition, this case highlights the differential diagnosis of metastatic carcinomas that display a CK7/CK20 positive immunophenotype including transitional cell carcinoma, pancreatic carcinoma, cholangiocarcinoma and rare gastric carcinomas.

Signet-ring cell ependymoma with intratumoral hemorrhage in the medulla oblongata

We report a case of signet-ring cell ependymoma of the medulla oblongata. The patient presented with acute paralysis of the soft palate and absent gag reflex resulting in respiratory distress after accidental inhalation of water. MRI revealed a large intra-axial mass with foci of intratumoral hemorrhage in the medulla oblongata. A subtotal resection was performed as histopathological findings on the frozen section were consistent with metastatic carcinoma. However, the final paraffin section showed an ependymoma with signet-ring cells. A total removal was then performed with preservation of the lower cranial nerves. Postoperatively, the patient made a slow but steady recovery, and was able to swallow both water and food within 3 months. Signet-ring cell ependymoma must be included in the differential diagnosis of metastatic carcinoma to the central nervous system.

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20− was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7−/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20−, whereas 19% (8 of 43) were CK7−/CK20+. All colorectal cancers metastatic to the ovary were CK7−/CK20+, except 1 case that was CK7−/CK20−. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7−/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma. HUM PATHOL 33:1078-1085. Copyright 2002, Elsevier Science (USA). All rights reserved.

Cytokeratins 20 and 7 in the differential diagnosis of metastatic carcinoma in cytologic specimens.

A series of 33 tumor cases (13 fine-needle aspirates and 20 effusion specimens) were evaluated for the expression of two cytokeratin (CK) subtypes; CK 20, expressed primarily in tumors of the GI tract, mucinous ovarian tumors and transitional cell carcinomas, and CK 7, found chiefly in non-GI tract adenocarcinomas, including breast and lung. CK 20 expression was demonstrated immunocytochemically in seven of seven metastatic colon and two of three metastatic transitional cell carcinomas tested. CK 20 was absent in all metastatic carcinomas of breast, ovary, lung, and uterus examined (23 cases). Anti-CK 7 stains were negative in four of six metastatic colonic carcinomas, with equivocal results in the remaining two cases. Metastatic lung, breast, and ovarian carcinomas were strongly positive for CK 7. This study demonstrates that the combined use of anti-CK 20 and anti-CK 7 antibodies is highly sensitive and specific for metastatic colonic adenocarcinoma in cytologic material and thus could play an important role in distinguishing this entity from other common primary carcinomas.

Metastatic prostatic carcinoma presenting as left-sided cervical lymphadenopathy: a series of 11 cases.

Eleven cases of metastatic prostatic carcinoma in cervical lymph nodes as a primary presenting sign were identified in a survey of 250 cervical lymph node biopsies from men. The diagnosis was clinically unsuspected in all cases. All occurred on the left side of the neck. These 11 cases represented 11% of all metastatic carcinomas in the neck and 20% of those with left-sided involvement. The diagnosis was readily confirmed by immunostaining for prostate specific antigen and prostate specific acid phosphatase. Six patients are alive and well at an average of 25.8 months and five others survived for an average of 34.4 months, the combined survival being 29.7 months. This contrasts with the dismal fate of patients with metastatic adenocarcinoma from other sites who all died at an average of 2 months from diagnosis. Prostatic carcinoma should always be considered in the differential diagnosis of metastatic carcinoma in cervical lymph nodes in elderly men, as appropriate treatment results in worthwhile prolongation of life.