What Does Clear Cell Carcinoma Mean

What Exactly Does Grade 1 2 3 4 Of The Tumor Mean In Clear Cell Renal Cell Carcinoma

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Who Gets Clear Cell Carcinoma Of Endometrium

• Clear Cell Carcinoma of Endometrium accounts for about 1-5% of all endometrial cancers in women
• Most of the cases are observed in women aged 50 years and older . Women under the age of 40 years are rarely diagnosed with cancers of the endometrium
• However, when there is an association with inherited genetic disorders, such as Cowden syndrome or Lynch syndrome, slightly younger women may be affected. In general, the age of onset of familial cancers is lower than the age for sporadic forms
• All racial and ethnic groups are affected by this cancer type the condition is observed worldwide in women

Met And Egfr Inhibitors

In addition to VEGF-TKI data on MET inhibition with tivantinib in comparison to a combination of tivantinib with the epidermal growth factor receptor inhibitor erlotinib were recently published . Although an earlier study with erlotinib as monotherapy indicated promising results with an ORR of 11%, the more recent study was stopped permanently after the interim analysis due to a lack of efficacy in both treatment arms. So far, the use of MET inhibitors or erlotinib is not recommended outside clinical trials.

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How Is Ccrcc Diagnosed

Patients with ccRCC may have pain or feel tired. Sometimes, patients do not have any noticeable symptoms. Symptoms can include:

• Blood in the urine
• Fever
• A lump in the side

For people without symptoms, these tumors can be discovered if the person has an imaging test for another reason.

Imaging: If are suspected to have clear cell renal cell carcinoma, your doctor will use imaging scans such as X-rays, CT or MRI to look at the size of the tumor. They will also check for signs that the tumor has spread to other parts of the body.

Biopsy: To check if the tumor is ccRCC your doctor will perform a biopsy, taking a small sample from the tumor with a needle. An expert, called a pathologist, will study cells from the sample under the microscope to see what kind of tumor it is.

What Is The Prognosis Of Clear Cell Carcinoma Of Endometrium

• The prognosis of Clear Cell Carcinoma of Endometrium depends upon a set of several factors that include:
• The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
• Stage of cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• FIGO grade of the tumor: Tumors that are graded 1 and 2 have better prognoses than grade 3 tumors
• Hormone-receptor status of the cancer such as estrogen receptor and progesterone receptor
• Cell growth rate of the carcinoma
• Menopausal status of the women
• Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
• Age of the individual: Older individuals generally have poorer prognosis than younger individuals
• Individuals with bulky disease have a poorer prognosis
• Involvement of the regional lymph nodes, which can adversely affect the prognosis
• Involvement of vital organs may complicate the condition
• The surgical respectability of the tumor
• Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
• Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• Progression of the condition makes the outcome worse

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About The Uterus And Endometrium

The uterus is a hollow organ, normally about the size and shape of a medium-sized pear. The uterus is where a fetus grows and develops when a woman is pregnant. It has 2 main parts :

• The upper part of the uterus is called the body or the corpus.
• The cervix is the lower end of the uterus that joins it to the vagina.

When people talk about cancer of the uterus, they usually mean cancers that start in the body of the uterus, not the cervix.

The body of the uterus has 2 main layers:

• The myometrium is the outer layer. This thick layer of muscle is needed to push the baby out during birth.
• The endometrium is the inner layer. During a woman’s menstrual cycle, hormones cause the endometrium to change. Estrogen causes the endometrium to thicken so that it could nourish an embryo if pregnancy occurs. If there is no pregnancy, estrogen is produced in lower amounts and more of the hormone called progesterone is made. This causes the endometrial lining to shed from the uterus and become the menstrual flow . This cycle repeats until menopause.

There is also a layer of tissue called the serosa which coats the outside of the uterus.

Adjuvant And Neoadjuvant Therapy

Adjuvant therapy, which refers to therapy given after a primary surgery, has not been found to be beneficial in renal cell cancer. Conversely, neoadjuvant therapy is administered before the intended primary or main treatment. In some cases neoadjuvant therapy has been shown to decrease the size and stage of the RCC to then allow it to be surgically removed. This is a new form of treatment and the effectiveness of this approach is still being assessed in clinical trials.

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How Does Ccrcc Form

Scientists are always working to understand how cancer forms, but it can be hard to prove. Because ccRCC can run in families, we know that changes in the VHL gene are important in causing ccRCC. The VHL gene is also changed in ccRCC from people without a family history of Von Hippel-Lindau syndrome. Scientists have learned a lot about what the VHL gene does in the body. This has given scientists clues about treatments to try for ccRCC.

Chromophobe Renal Cell Carcinoma

Chromophobe RCC comprises 3% to 5% of all RCCs and is associated with numerous chromosomal monosomies.153,164-169 Patients have an excellent prognosis.169-172 The cytoplasm stains diffusely positive with Hale colloidal iron stain.173

Most aspirates are very cellular, consisting of tumor cell groups and isolated tumor cells that are generally less cohesive than the cells aspirated from clear cell RCC .174-177 The cells of chromophobe RCC may have a koilocytic appearance as a result of their cytoplasmic and nuclear features, resembling koilocytes seen in Pap smears. These consist of very large cells with prominent cell membranes and abundant fluffy cytoplasm, which is granular but not uniformly so. There may be perinuclear clearing of the cytoplasm. Binucleation is common. Although some nuclei can be very round and bland, in general the nuclei of chromophobe carcinoma have markedly irregular outlines, fine chromatin that can be either very light or dark and hyperchromatic, and marked size variation. Prominent nucleoli are uncommon. These nuclear features are distinctly different from those of most other RCCs. Eosinophilic variants have more granular cytoplasm, whereas typical variants have more clear cytoplasm. The cells stain diffusely positive in a cytoplasmic pattern with Hale colloidal iron stain.

Fig. 4.24. Chromophobe renal cell carcinoma.

Fig. 4.25. Chromophobe renal cell carcinoma.

Fig. 4.26. Chromophobe renal cell carcinoma.

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Benign And Malignant Tumors

Several benign and malignant tumors can have a clinical appearance similar to that of SGC. These include BCC, SCC, melanoma, Merkel cell carcinoma, lymphoma, sweat gland neoplasm, junctional squamous papilloma, hereditary benign intraepithelial dyskeratosis, metastatic carcinoma, and other rare tumors.1

Basal cell carcinoma

The nodular BCC is more common on the lower lid and is white rather than yellow. BCC is also more likely to become ulcerated than SGC. Although diffuse sclerosing BCC may closely simulate SGC, it very rarely exhibits diffuse invasion of the conjunctiva. Histologically, BCC typically shows peripheral palisading of nuclei and retraction artifact that are not seen in SGC.

Squamous cell carcinoma

SCC is more superficial and lacks a yellow color. Conjunctival intraepithelial neoplasia can be very similar to diffuse epithelial invasion by SGC, except for eyelid involvement, which is less likely to be present in SGC. Histopathologically, SCC is the lesion most often confused with SGC.6,14,15 Unlike SGC, SCC cells have more abundant eosinophilic cytoplasm, lack lipid vacuoles, and demonstrate eddy formation and keratin cysts.

Melanoma

Nodular or diffuse cutaneous melanoma in the eyelid or conjunctiva can usually be distinguished from SGC by its black or brown pigmentation, but amelanotic melanoma can resemble SGC.

Other tumors

Yaohui G. Xu, … Gary S. Wood, in, 2020

Clear Cell Papillary Renal Cell Carcinoma

Jianping Zhao, Eduardo Eyzaguirre Clear Cell Papillary Renal Cell Carcinoma. Arch Pathol Lab Med 1 September 2019 143 : 11541158. doi:

Clear cell papillary renal cell carcinoma is a recently recognized entity and represents the fourth most common variant of renal cell carcinoma . It has unique morphologic and immunohistochemical features and demonstrates an indolent clinical behavior. Microscopically, it may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC with clear cell changes. A high index of suspicion is required to keep ccpRCC in the differential diagnosis of RCCs with features of clear cell and/or papillary architecture. In equivocal cases, immunohistochemistry is generally sufficient to substantiate the diagnosis of ccpRCC. In this review, we discuss the clinical, gross, and histopathologic features, immunohistochemical and genetic profiling, and prognosis of ccpRCC.

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How Is Clear Cell Carcinoma Of Endometrium Diagnosed

There is a variety of tests healthcare providers may use to detect, locate, and diagnose Clear Cell Carcinoma of Endometrium, and assess if it has potentially spread to other regions. A surgical procedure called a biopsy is the main test a healthcare provider relies on to make a definitive diagnosis of Clear Cell Carcinoma of Endometrium.

The diagnostic tools may include:

• A thorough physical examination and a complete medical history evaluation is very vital to the diagnosis
• Pelvic examination: During a pelvic examination, a physician exams the uterus, vagina, ovaries, fallopian tubes, bladder, and rectum to check for any abnormal changes in these organs
• Complete blood count with differential of white blood cells
• Liver function test
• Inhibin
• Estrogen and testosterone levels

Note:

How Is Clear Cell Sarcoma Treated

Treatment for each person will be unique. You should go to an expert in sarcoma treatment to decide the best approach for your tumor. You can contact MyPART for help finding experts near you.

Surgery: Surgery to remove the tumor and some healthy tissue around it is the best treatment for CCS. In some cases, an entire arm or leg may need to be amputated. If some cancer cells are left behind, there is a greater chance of the cancer coming back in the same spot. Or, it may spread to a different part of the body.

Radiation therapy: Radiation therapy can be used before or after surgery if doctors think that surgery alone will not remove all the tumor cells. Even so, we dont know if radiation therapy will help you live longer.

Chemotherapy: When surgery is not possible or when the cancer has spread, chemotherapy can be used to treat CCS. But it does not seem to be an effective way to treat CCS.

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Pathology And Pathways Of Spread

In common nodular BCC, nodular masses of basaloid cells extend from the epidermis or outer root sheath into the dermis with surrounding connective tissue stroma . Peripheral palisading of cells and stroma retraction artifact aid in diagnosis. There are several subtypes histologically, including pigmented, superficial, nodular, micronodular, infiltrative, morpheaform, and adenocystic, etc. Morpheaform BCC is distinct in that strands of deeply infiltrating tumor cells are embedded in a dense fibrous tissue stroma. The morpheaform and infiltrative types are in general the most locally invasive variants of BCC. It is common for BCCs to show mixed histologic patterns of these various types.74 Even the less invasive variants may invade deeply when located in regions of embryonic fusion planes, such as around the nose and ears. BCC can be locally aggressive but metastasis is rare, with rates ranging from 0.003% to 0.55%.75

Gary S. Wood, … Stephen N. Snow, in, 2014

What Is The Prognosis For People With Ccrcc

The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as

• Where the tumor is in your body
• If the cancer has spread to other parts of your body
• How much of the tumor was taken out during surgery

If you want information on your prognosis, it is important to talk to your doctor. NCI also has resources to help you understand cancer prognosis.

Doctors estimate ccRCC survival rates by how groups of people with ccRCC have done in the past. Because there are so few pediatric ccRCC patients, these rates may not be very accurate. They also dont take into account newer treatments being developed.

With this in mind, ccRCC patients with smaller tumors have a better chance of survival than patients with larger tumors. The 5-year survival rate for patients with ccRCC is 50-69%. When ccRCC is already large or has spread to other parts of the body, treatment is more difficult and the 5-year survival rate is about 10%.

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How Can Clear Cell Carcinoma Of Endometrium Be Prevented

Currently, there are no known and available methods to prevent Clear Cell Carcinoma of Endometrium. However, various steps may be taken to help decrease the incidence risk:

Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations are mandatory, due to risk of metastasis and recurrence of the tumor, for individuals who have already endured the cancer. Often several years of active vigilance is necessary.

Types Of Endometrial Cancer

Endometrial cancer starts in the cells of the inner lining of the uterus . This is the most common type of cancer in the uterus

Endometrial carcinomas can be divided into different types based on how the cells look under the microscope. They include:

• Adenocarcinoma
• Uterine carcinosarcoma or CS
• Squamous cell carcinoma
• Transitional carcinoma
• Serous carcinoma

Clear-cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, and serous adenocarcinoma are less common types of endometrial adenocarcinomas. They tend to grow and spread faster than most types of endometrial cancer. They often have spread outside the uterus by the time they’re diagnosed.

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Prognosis And Predictive Factors

Patients with clear cell renal cell carcinoma tend to have a worse prognosis than patients with other histologic subtypes of RCC, with 5-year disease-specific survival rates of 50-69%, compared with 67-87% for papillary RCC and 78-87% for chRCC. However, analysis of 1000 patients showed very similar 5-year disease-specific survival rates for CCRCC and papillary RCC once metastatic disease was present.

Multivariate analyses indicate that histologic RCC subtype has no significant independent value for predicting cancer-specific survival because prognosis is primarily dependent upon TNM stage and Fuhrman nuclear grade. Multivariate analysis specifically of CCRCC cases shows that in addition to the 3 separate components of tumor staging , other significant independent predictors of poor prognosis are nuclear grade, tumor size, and the presence of histologic necrosis or sarcomatoid differentiation.

Rhabdoid differentiation is also observed in CCRCC and seems to impart a poor outcome similar to sarcomatoid change however, this factor has not yet been tested in predictive models. Interestingly, histological necrosis is seen more commonly in papillary RCC but is not a significant predictor of poor prognosis for papillary RCC, even in univariate analyses.

References

Comparing Ccoc And Ccrcc

In the preceding paragraphs, we presented two diseases: ccRCC, the most common subtype of kidney cancer, and CCOC, which represents 10% of EOCs. Although we appreciate that each type of cancer is its own disease, there may be shared targetable features. In this section, we compare the molecular and genomic characteristics of these two cancers in order to understand them beyond their morphological similarities.

Clinically, although the incidence of renal cancer has increased, the mortality due to this cancer has decreased , partly because of earlier incidental detection, and partly because of increased therapeutic options. In contrast, the mortality due to ovarian cancer has remained high over the past 30 years. Although CCOC is discovered at an earlier stage than other EOC subtypes, 40% of patients are still diagnosed at stage IIIâIV . Moreover, as conventional taxane-based and platinum-based chemotherapy remain the gold-standard regimen for ovarian carcinomas, the outcome for CCOC patients remains suboptimal, owing to the inherent chemoresistance of this malignancy.

Histologically, CCOC and ccRCC often show similar features, and several groups have studied IHC markers to differentiate the two malignancies -. Of these markers, positivity for RCC markers and CD10 were the main factors distinguishing ccRCC from CCOC. Despite these differences, there are also similarities. IHC markers pertinent to CCOC and ccRCC are summarized in Tables and .

Figure 2

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