Ovarian squamous cell carcinoma (oSCC) or squamous ovarian carcinoma (SOC) is a rare tumor that accounts for 1% of

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

s. Included in the

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

's classification of ovarian cancer, it mainly affects women above 45 years of age. Survival depends on how advanced the disease is and how different or similar the individual

cancer cell Cancer cells are cells that divide continually, forming solid tumors or flooding the blood or lymph with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, an ...

s are. Squamous ovarian

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...

is a recognized but uncommon diagnosis, often originating from a transformation of mature cystic teratoma (MCT). Unlike other

squamous cell carcinomas Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in Epithelium#Cell types, squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in ...

, factors like UV exposure and tobacco use play a less significant role. Chronic inflammation in MCT and

human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...

(HPV) infection are linked to its development. The tumor emerges through metaplasia of the ovarian surface epithelium. While MCT is the primary source in most cases, others are associated with

endometriosis Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...

Brenner tumor Brenner tumours are an uncommon subtype of the Surface epithelial-stromal tumor, surface epithelial-stromal tumour group of Ovarian cancer, ovarian neoplasms. The majority are benign, but some can be malignant. They are most frequently found incid ...

, and rare

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

from other organs can also lead to squamous ovarian carcinoma. Treatment for oSCC involves surgery,

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

, and

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

, but efficacy of these treatments is unclear. While there is no well-studied chemotherapy regimen for ovarian SCCs,

platinum-based chemotherapy Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemothe ...

is often used. The earliest reported instance of pure primary SCC was by Ben-Baruchet in 1988; oSSC emerging from pre-existing lesions have been recorded since the early 1950s.

Pathology

Mature cystic teratoma

Mature cystic teratoma A teratoma is a tumor made up of several types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the tailbone (where it is known as a sacrococcygeal teratoma), ovary, or testicle. Symptoms Symptoms may be minimal ...

(MCT) is a benign (non-cancerous) tumor that develops from at least two of the embryonic germ cell layers. They are characterized by a lining of

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

and can contain many different tissue types. Although the majority of MCT cases are non-malignant, approximately 0.17-2% may undergo malignant transformation, with

squamous cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

being the most prevalent, constituting 80% of such transformations. The clinical presentation of oSCC development within MCT lacks specificity, often resulting in the inadvertent discovery of early-stage tumors during routine examinations or postoperative assessments. In advanced cases, patients may exhibit palpable masses, abdominal swelling, and pain, potentially leading to acute abdominal complications due to tumor involvement.

Brenner tumor

s (BT) are infrequent ovarian growths composed of specialized ovarian cells surrounded by dense fibrous tissue. Typically small (less than 2 cm), these tumors are often discovered incidentally in women without apparent symptoms. However, when a BT is borderline or malignant, indicating a potential for cancer, it may lead to symptoms such as an abdominal lump, abdominal pain, and

post-menopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

bleeding. Less common signs include nausea, vomiting, back pain, bowel problems, reduced appetite, and weight loss. Differentiating between benign (non-cancerous) and malignant (potentially cancerous) BTs poses a challenge as they appear similarly in medical images. The definitive diagnosis involves examining tissue under a microscope (

histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

). Benign BTs exhibit a consistent fibrous structure, a distinctive characteristic. They may also manifest as a cystic mass with multiple compartments, particularly associated with other ovarian growths.

Endometriosis

oSCC tumors from

are rare. There are criteria to determine if oSCC comes from endometriosis. Individuals with this type of cancer are usually under 50, have a more severe form of the disease, and often feel abdominal pain.

Screening and diagnosis

Similar to other ovarian cancers patients can undergo a series of tests to identify characteristics and/or markers. This test includes a

pelvic exam A pelvic examination is the physical examination of the external and internal female pelvic organs. It is frequently used in gynecology for the evaluation of symptoms affecting the female reproductive and urinary tract, such as pain, bleeding, di ...

, imaging (CT, MRI, ultrasound),

blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...

, and in some cases

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

with

. Diagnosing this condition remains challenging as preoperative imaging and laboratory tests lack specific indicators.

Computed tomography

Computed tomography A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

(CT) scans is a diagnostic x-ray procedure that generates detailed cross-sectional images of the body, facilitating the detection of potential

spread to other organs. While CT scans may not effectively visualize small ovarian tumors, they have the capability to detect larger tumors and evaluate their potential invasion into nearby structures. Additionally, CT scans can identify enlarged

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

s, signs of cancer spreading to the liver or other organs, and indications of an ovarian tumor impacting the kidneys or bladder. Although CT scans are not commonly used for biopsying ovarian tumors, they can be utilized in the biopsy of suspected

metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

through a technique known as CT-guided

needle biopsy Needle or Needles may refer to: Crafting * Crochet needle, a tool for making loops in thread or yarn * Knitting needle, a tool for knitting, not as sharp as a sewing needle * Sewing needle, a long slender tool with a pointed tip * Trussing needle, ...

. The difficulty in screening for SCC revolves around the creation of effective strategies with a positive predictive value. The timing aspect is crucial due to the lack of a specific timeframe for the onset of invasive disease or the interval stage between stage I and stage III

s. Ultrasound screening provides a detailed view of the ovaries, identifying morphologic changes as potential signs of malignancy. Key diagnostic factors include the presence of abnormalities, ovarian size, blood flow, and abdominal/pelvic fluid. The persistence of abnormalities after four to six weeks may decrease the occurrence of false positives. Screening protocols, often based on morphologic indices, utilize

transvaginal ultrasound Vaginal ultrasonography is a medical ultrasonography that applies an ultrasound transducer (or "probe") in the vagina to visualize organs within the pelvic cavity. It is also called transvaginal ultrasonography because the ultrasound waves go ''a ...

findings like cyst wall structure, septation, papillary projections, echogenicity, and ovarian volume to effectively detect malignancy.

Magnetic resonance imaging

Although magnetic resonance (MRI) scans are not commonly employed for ovarian cancer detection, the majority of ultrasound-detected ovarian masses are usually benign. The combined approach of ultrasound with

Doppler The Doppler effect (also Doppler shift) is the change in the frequency of a wave in relation to an observer who is moving relative to the source of the wave. The ''Doppler effect'' is named after the physicist Christian Doppler, who described ...

, along with the selective use of contrast-enhanced MRI, proves to be an efficient diagnostic method for identifying benign adnexal masses with distinctive features, including functional masses, dermoid, endometrioma, fibroma, pedunculated fibroid,

hydrosalpinx A hydrosalpinx is a condition that occurs when a fallopian tube is blocked and fills with serous or clear fluid near the ovary (distal to the uterus). The blocked tube may become substantially distended giving the tube a characteristic sausage-lik ...

, and peritoneal inclusion cysts. This integrated diagnostic strategy is effective in preventing unnecessary surgical intervention. Additionally, the use of MRI contributes to a decrease in false-positive diagnoses, ultimately reducing the overall number of unnecessary surgical procedures related to ovarian masses.

Histopathology

Pathologic examination of biopsies helps distinguish between benign and malignant lesions, aiding in the identification of different cancer types. Larger excisional specimens, known as resections, provide comprehensive information about the cancer, its sub classification, histologic grading, and the extent of its spread, contributing to the pathologic staging. In cases where visible growth or malignant transformation is not apparent, a precise grossing and thorough histopathological examination are essential for an accurate diagnosis. Additionally, conducting situ hybridization for

HPV Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and ...

DNA is crucial to rule out the potential involvement of papillomavirus in this condition. To distinguish between primary ovarian serous carcinoma (OSC) and metastatic squamous cell carcinoma (SCC), various immunohistochemical markers such as

PAX8 Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the ''PAX8'' gene. Function This gene is a member of the paired box ( PAX) family of transcription factors. Members of this gene family typically encode proteins ...

p16 p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the ...

WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...

, ER,

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

, and CK5/6 are utilized. The p53/p16 index was recognized as a valuable indicator for high-grade OSC, demonstrating diffuse p53 expression or complete absence (null type) along with diffuse p16 expression. Additional treatment options suggest the use of targeted therapies for squamous cancers, particularly those with elevated

epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor (biochemistry), receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligand (biochemistry ...

(EGFR) levels, which remains somewhat limited. Elevated EGFR expression is identified in squamous cell carcinomas of the head and neck as well as the

cervix The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time ...

, indicating potential benefits from EGFR inhibition regardless of

tumor status.

Management

oSCC exhibits locally invasive characteristics, with tumors demonstrating invasiveness or adherence to the adjacent

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

, pelvic structures, and colonic

peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...

, making surgery the crucial treatment. The standard approach for treating the malignant transformation of mature cystic teratoma of the ovary (MCTO) involves extensive surgery and subsequent chemotherapy, especially for advanced cases. Recommended for patients not seeking fertility, the surgical procedure includes bilateral

salpingo-oophorectomy In medicine, salpingo-oophorectomy is the removal of an ovary and its fallopian tube. This procedure is most frequently associated with prophylactic surgery in response to the discovery of a BRCA mutation, particularly those of the normally tumo ...

, hysterectomy, comprehensive surgical staging, and lymphadenectomy. Following surgery, advanced cases receive adjuvant chemotherapy with

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

and

carboplatin Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...

, although the overall prognosis is generally less favorable than that of common epithelial ovarian cancer.

Surgery

Treatment for

often involves surgical procedures to diagnose and remove affected tissues. The choice of surgery depends on the cancer's stage, type, and grade, offering options such as unilateral or bilateral

oophorectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), historically also called ''ovariotomy'', is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference ...

, along with the removal of the fallopian tubes, uterus, and omentum. In cases of low-grade cancers, fertility preservation may be possible, but the presence of microscopic

introduces the need for additional surgery. Unilateral surgery is typically employed for germ cell tumors. Achieving complete

cytoreduction Debulking is the reduction of as much of the bulk (volume) of a tumour without the intention of a complete eradication. It is usually achieved by surgical removal. When performed for curative intent, it is a different procedure, which is called sur ...

is essential for managing advanced epithelial ovarian cancer, while debulking surgery aims to remove as much tumor as possible, enhancing the effectiveness of chemotherapy. An alternative approach involves interval debulking surgery, which combines

neoadjuvant chemotherapy Neoadjuvant therapy is the administration of therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate. Neoadjuvant therapy aims to reduce the size or ...

with post-debulking chemotherapy. While

laparoscopic Laparoscopy () is an operation performed in the abdomen or human pelvis, pelvis using small Surgical incision, incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few ...

surgery is suitable for early-stage cancer, advanced cases require more extensive procedures like

lymphadenectomy Lymphadenectomy, or lymph node dissection, is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in ...

. Secondary surgery may be an option for recurrent cases, effectiveness depending on factors such as surgical technique and the extent of the disease. Oophorectomy's primary side effect, early

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

, can be alleviated with hormone replacement therapy. Hospitals with higher surgical volumes tend to have better surgery outcomes, and the choice between laparoscopy and laparotomy for stage I ovarian cancer remains uncertain. Aggressive surgeries are associated with improved outcomes in advanced stages, despite the presence of perioperative

Lymphadenectomy

Lymphadenectomy Lymphadenectomy, or lymph node dissection, is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in ...

, or the surgical removal of

s, is commonly undertaken in cancer management, with regional and radical dissections differing in the extent of node removal. A

meta-analysis Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...

research of published

randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...

s comparing lymphadenectomy versus no lymphadenectomy in epithelial cancers of the ovary, suggest that overall survival did not demonstrate significance. However, the meta-analysis is unique for focusing on randomized trials, using hazard ratios, and treating ovarian carcinoma as a unified entity. In some cases, complications of lymphadenectomy include lymphedema, and the effectiveness of wound drainage in reducing complications after groin lymph node dissection remains uncertain.

Ionization, radiation and chemotherapy

Typically, a combination of treatments, including surgery, external beam radiotherapy, brachytherapy, and

, is employed for these cancers. This understanding could potentially enhance control over the local region, improve quality of life, and increase survival rates. Nevertheless, there is some indication, supported by certain case series, that

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

, particularly when paired with concurrent chemotherapy following aggressive cytoreduction, may be beneficial for certain cases of oSCC originating from teratomas, given the radiosensitive nature of this tumor. There is no widely accepted chemotherapy regimen used for oSCC, both because of its heterogeneous histology and rarity, but treatment often includes a

drug. Reported regimens include the combination of

and

(TC) and the combination of

bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , C=55 , H=84 , N=17 , O=21 , S=3 , SMI ...

etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...

, and

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

(BEP).

Immunotherapy

Immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

's adoption in platinum-resistant ovarian cancer remains unsupported by studies, prompting a need for further investigation. Nonetheless, evidence indicates that combining chemotherapy with the humanized anti-

VEGF Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...

monoclonal antibody, bevacizumab, in the treatment of recurrent, persistent, or metastatic cervical cancer results in a 3.7-month enhancement in overall survival.

Prognosis

Overall survival of treatments for Ovarian Squamous Cell Carcinoma

Ovarian squamous cell carcinoma typically presents with a mean tumor size of 14.8 cm, and overall survival does not vary based on tumor size. Clinical manifestations include

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...

and a palpable abdominal mass. The

cancer stage Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ...

is correlated with the time of diagnosis, revealing that higher stages and delayed diagnoses are associated with a worse

prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...

Hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...

reduces the risk of death, while

does not demonstrate improved survival. Fertility-sparing surgery shows no difference in mortality compared to radical surgery in patients under 45.

Adjuvant chemotherapy Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in ...

enhances survival in advanced stages, with

linked to a better prognosis.

Radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

and

chemoradiotherapy Chemoradiotherapy (CRT, CRTx, CT-RT) is the combination of chemotherapy and radiotherapy to treat cancer. Synonyms include radiochemotherapy (RCT, RCTx, RT-CT) and chemoradiation. It is a type of multimodal cancer therapy. Chemoradiation can be ' ...

do not improve survival. Poor prognostic factors include age over 45 or 55, advanced staging, larger tumors, high cancer grade, absence of hysterectomy, presence of residual tumor lesions, lack of adjuvant chemotherapy, and the use of non-platinum-based chemotherapy. In cases of recurrence, secondary cytoreductive surgery may be considered, revealing efficacy in selected cases with recurrent malignant transformation of MCTO.

References

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